Brain and Mind Centre Annual Report

Our sydney.edu.au Brain and Mind Centre Annual Report 2015-16 patients’ success sydney.edu.au/brain-mind sydney.edu.au/brain-mind 0774 2 9351 +61 The University of Sydney Contact us is our greatest reward. Forest Stewardship Council (FSC®) is a globally recognised certification overseeing all fibre sourcing standards. This provides guarantees for the consumer that products are made of woodchips from well-managed forests and other controlled sources with strict environmental, economical and social standards. Contents Welcome...... 2 Co-Directors...... 2 Message from Vice Chancellors...... 3 - Overview...... 4 Teams and key research themes...... 4 Partnerships...... 6 - Child Development and Behaviour...... 8 Our core business...... 9 Highlights...... 10 Key projects and clinical trials...... 12 2017 and beyond...... 13 Key publications...... 14 - Youth Mental Health...... 18 Our core business...... 18

Brain and Mind Centre Annual Report 2015-16 Highlights...... 20 2017 and beyond...... 22 Key projects and clinical trials ...... 23 Key publications...... 25 - Neuroimmunology...... 29 Our core business...... 29 Highlights...... 30 2017 and beyond...... 32 Key publications ...... 33 - ForeFront Ageing and Neurodegeneration...... 37 Our core business...... 37 Highlights...... 40 sydney.edu.au/brain-mind sydney.edu.au/brain-mind 0774 2 9351 +61 2017 and beyond...... 45 Key projects and clinical trials...... 46 Key publications...... 47 - The Lambert Initiative for Cannabinoid Therapeutics...... 50 Our core business...... 51 Highlights...... 52 2017 and beyond...... 54 Key publications...... 55 - Technical Facilities...... 58 Our core business...... 58 Highlights...... 61 2017 and beyond...... 63 Key publications...... 64 - Brain and Mind Centre...... 66 Our donors...... 66 Our teams...... 70 Welcome Co-Directors

Welcome to the Brain and Mind Centre Annual Report, which celebrates our many achievements over the past sydney.edu.au/brain-mind two years.

Our Co-Directors Professors Ian Hickie (left) and Matthew Kiernan.

Becoming Brain and Mind Centre As part of this emphasis on The vast amount of peer-reviewed in 2015 marked a radical shift in growing our research potential, papers highlighted in this direction towards developing into we welcome the arrival of publication is testament to the a truly multidisciplinary centre ForeFront, led by Professors tireless work of our researchers that encourages participation Glenda Halliday, John Hodges who have won many grants over from research teams across the and Associate Professor Olivier the past two years. Our work has University of Sydney campuses at Piguet. This team is committed been noticed nationally too – Camperdown and Mallet Street, to discovering early detection Prime Minister Malcom Turnbull Westmead, Nepean, Cumberland methods, identifying new committed $30 million to Project and beyond. By entering into our treatments and understanding Synergy in 2016. This project is network, researchers have access the underlying mechanisms of led by Professor Jane Burns, a to information on relevant funding neurodegenerative disease. relentless innovator in the field of opportunities, news, and events. We are also proudly watching digital mental health. They also have the opportunity the progress of the Lambert Brain and Mind Centre Annual Report 2015-16 to partner with other research Initiative, formed in 2015 after an To help communicate our institutes, local health districts, unprecedented personal donation successes and to further boost government, industry and to support research into the use our profile, as well as making our the community. of medicinal cannabis. patient services more accessible, we are have redeveloped our Most importantly, our researchers We welcome Professor Markus website and social media. are working as part of an Leweke to the role of Chair academic community that is of Youth Depression Studies. We hope you enjoy this focused on finding solutions Joining us from the Central publication and look forward to the most challenging health Institute of Mental Health in to our continued successes. problems in the world. Our unique Mannheim, Germany, Professor approach combines effective Leweke plans to work closely with clinical care with cutting-edge the Sydney Local Health District research, providing researchers to set up a clinical service unit at with live data and giving clinicians the Marie Bashir Centre. Another access to innovative treatments appointment to celebrate is Niels Professor Matthew Kiernan and interventions as soon as they Buus to the St Vincent’s Chair Co-Director, Translation and Discovery The University of Sydney are developed. We encourage of Mental Health Nursing, who researchers to join us in our will work to develop new family multidisciplinary approach to and community-based models tackling the challenges of brain of mental healthcare. and mind disorders.

Professor Ian Hickie AM Co-Director, Health and Policy Page 2 Welcome Message from the University

The University of Sydney officially launched Brain and Mind Centre in July 2015 to address disorders of the brain and mind, expand the breadth and depth of multidisciplinary research and set new standards in brain and mind sciences, both in Australia and internationally.

Previously known as the Brain and With Co-Directors Professors

Mind Research Institute (BMRI), Matthew Kiernan and Ian Hickie Welcome the Centre was created as a leading the way, Brain and Mind flagship multidisciplinary initiative, Centre is breaking new ground in one of the key recommendations research and development. We of the Health and Medical are excited to present a snapshot Research Strategic Review. The of this incredible research aim: to leverage the University's conducted throughout 2015 existing research excellence and 2016. in order to deliver significant Professor Duncan Ivision Deputy Vice-Chancellor, Research benefits to society. University of Sydney The Centre’s strategic objectives are focused on creating an enduring program of research and education that responds directly Professor Duncan Ivision to 21st century societal challenges Deputy Vice-Chancellor, Research of the brain and mind sciences. University of Sydney

Message from the University

Professor Laurent Rivory Pro Vice-Chancellor, Strategic Collaborations and Partnerships Professor Laurent Rivory University of Sydney Pro Vice-Chancellor, Strategic Collaborations and Partnerships University of Sydney Page 3 Overview Teams and key research themes

The University of Sydney’s Brain and Mind Centre is sydney.edu.au/brain-mind a global leader in research into, and treatment of, disorders of the brain and mind. Our vision is to see a world where people can reach their full potential and play an active role in society.

Our multidisciplinary research teams are at Brain and Mind Centre represents a virtual the forefront of brain and mind sciences. network of academics across University We work to find answers to some of the of Sydney, Westmead Hospital, Nepean world’s most pressing health concerns, Hospital, Royal North Shore Hospital, including childhood development and Kolling Institute, Concord Repatriation behaviour disorders, youth mental General Hospital and Sydney Adventist health and addiction, and ageing and Hospital. The Centre is also affiliated with neurodegeneration such as dementia, Sydney Health Partners and Sydney local multiple sclerosis and Parkinson’s disease. health districts. Brain and Mind Centre Annual Report 2015-16

Our large-scale research is collaborative and innovative, our laboratories are state-of–the-art and our clinics are a valuable resource for people in need. Our visionary research teams partner with the community, industry, government and diverse branches of academia to make a real difference to people’s lives. The University of Sydney

Testing at the Autism Clinic for Translational Research. Page 4 Overview Teams and key research themes

Partnering with patients to find solutions to world health problems. Page 5 Overview Partnerships

Our cutting-edge research is underpinned by strategic partnerships. New solutions to help people in need require new collaborations - few medical discoveries are made in isolation. sydney.edu.au/brain-mind

Brain and Mind Centre is uniquely positioned for translational research that makes a real difference to people’s lives. Our dedicated laboratories are co-located with clinical services. This means we can integrate cutting-edge research with safe and effective clinical care. We leverage our research capacity by joining forces with the community, healthcare providers, industry, government and researchers from across the world to provide the best possible outcomes for people affected by brain and mind disorders.

Connecting with the community Partnering with industry We pride ourselves on partnering with the Brain and Mind Centre works closely with community to inform our research. We a variety of progressive companies to work directly with patient communities to translate new technologies and research provide expert clinical care and partner discoveries into innovations that benefit the with organisations such as MS Australia and economy and society. By bringing together Brain and Mind Centre Annual Report 2015-16 Parkinson’s NSW to ensure our expertise is research expertise with commercial clout, available to those who need it most. cutting-edge treatments for brain and mind disorders can reach the people that Our Youth Mental Health team works need them. closely with headspace, the National Youth Mental Health Foundation, providing Our multiple sclerosis research group has early intervention and mental health established successful partnerships with services for 12 to 25 year olds. The Novartis, Biogen and Sanofi Genzyme, Camperdown headspace clinic is located leading to funding for research trials and at Brain and Mind Centre, facilitating patient access to new drugs. continuous improvements to mental health services for the benefit of young people Similarly, our Youth Mental Health team has across Australia. partnered with PricewaterhouseCoopers to develop InnoWell, a new company championing digital healthcare.

We are proud to partner with Southern

The University of Sydney Radiology, one of Australia’s largest medical imaging providers. By working with their team of specialist diagnostic imaging radiologists, we can pool our resources and work together to study changes that occur in the brain. Page 6 Professor Ian Hickie AM with researchers in our Youth Mental Health and Technology team. Overview Overview

Collaborating with a global Working alongside health services academic network We work closely with the Sydney Local Our researchers partner with fellow Health District, Northern Sydney Local academics, institutes and universities from Health District, Western Sydney Local across Australia and the world. By sharing Health District and the Sydney Children’s knowledge, resources and facilities, we Hospitals Network, all of which are part offer the best chance of finding solutions of Sydney Health Partners, a collaboration to some of society’s greatest health between the University of Sydney and challenges. We are part of the Group its affiliated medical research institutes. of Eight (Go8) in Australia, a coalition of In 2015, Sydney Health Partners was research-intensive Australian universities recognised as a National Health and and their affiliates, as well as leading Medical Research Council Advanced Health institutions from across the world. Research and Translation Centre – one of only four in Australia. We also work closely with the Woolcock Institute. In 2016, the Woolcock NeuroSleep Clinic was established and is now located at Partnerships Brain and Mind Centre’s Camperdown site to advance research in translational sleep and circadian neurobiology.

Similarly, the Cerebral Palsy Alliance Research Institute employs a number of researchers across disciplines, dedicated to improving outcomes for patients. In 2015, Cerebral Palsy Alliance formed an affiliation with the University of Sydney and a branch is now located at Brain and Mind Centre’s Camperdown research site.

Page 7 Child Development and Behaviour _

Enhancing children’s wellbeing to prevent problems in later life. The University of Sydney Page 8 Child Development and Behaviour Our core business

Our team brings together internationally regarded clinical researchers in child development to reduce the impact of vulnerabilities such as social problems, autism, disruptive behaviour, emotional problems and impulsivity/hyperactivity.

Enhancing children’s wellbeing A neurobiological focus Our clinical researchers specialise in We investigate key neurobiological markers developing innovative assessments and (that is, biological characteristics) of treatments for child mental health. emotional, behavioural and social problems Child Development and Behaviour At the same time, we work to identify in children. the mechanisms that contribute to vulnerability, resilience and development This knowledge of biological markers means in children and their families. we can more effectively identify which children benefit from different types of The team is led by child psychologists treatments, as well as understand and track Professors Mark Dadds and Adam Guastella, how these treatments improve outcomes. and Associate Professor David Hawes. A focus on positive parenting An individualised approach and families to child mental health Many of the best evidence-based Rather than working within rigid interventions for child mental health diagnostic categories (such as autism, problems work by engaging with families. conduct disorder, anxiety or attention Our work is centered on building resources deficit hyperactivity disorder), we assess in parents and families to help foster children who present with a broad range healthy development and overcome early- of emotional and social development onset problems in children. Our team has concerns and design the most effective developed and evaluated brief evidence- intervention based on the unique needs of based parenting interventions that each child. create optimal environments for positive

child development. Our core business We recognise that there is significant overlap among many mental health conditions in childhood. Our approach provides a more effective way to prevent and manage mental health concerns in children.

Professor Adam Guastella demonstrates the MRI scanner. Page 9 Child Development and Behaviour Highlights

Opening the Child A new team is born Behaviour Research Clinic New therapies for autism 2015 saw the appointment of The Child Behaviour Research In a world-first, Professor Adam Professor Mark Dadds to Brain Clinic (Co-Directed by Professor Guastella, NHMRC Career sydney.edu.au/brain-mind and Mind Centre. As the Principal Mark Dadds and Associate Development Fellow, has used Research Fellow at the National Professor David Hawes) is a a randomised controlled trial Health and Medical Research state-of-the-art, custom- to show the potential benefit of Council (NHMRC), Professor designed research clinic focused a medication to improve social Dadds is a distinguished leader on developing, evaluating and responsiveness in young children in clinical child psychology, disseminating novel treatments for with autism. Currently, autism specialising in early intervention young children with behavioural affects one in 88 Australians. and the prevention of mental and emotional problems. health problems. In this groundbreaking study, The Child Behaviour Research oxytocin was administered Professor Dadds’ research Clinic was officially opened in intra-nasally and found to be focuses on the development of 2016 by former federal minister well tolerated in young children novel treatments for children and for health and aged care, Sussan with autism. Parents reported young adults with behavioural Ley. The Clinic represents Brain their children to be more socially and emotional problems. His and Mind Centre’s commitment responsive at home. Blind appointment has strengthened to shaping the next generation independent clinician ratings Brain and Mind Centre’s existing of mental healthcare for also supported improved social research and clinical capacity young people. responsiveness in the clinic. in the area of childhood mental health. The trial has been expanded to Brain and Mind Centre Annual Report 2015-16 include larger trials of longer The formation of the Child acting oxytocin therapies. This Development and Behaviour Team research could represent a major brings together the expertise of advance in the development of Professor Mark Dadds, Professor medical treatments for the social Adam Guastella, Associate deficits that characterise autism. Professor David Hawes and their research groups, in a collaborative program of research. The University of Sydney Page 10 Award-winning researchers In 2015, Professor Dadds was awarded the Distinguished Career Award from the Australian Association of Cognitive and Behaviour Therapy.

In 2016, Professor Dadds was also made an Inaugural Honorary Fellow of the Australian Association of Cognitive and Behaviour Therapy, and received the inaugural Media Award for Public Engagement with Psychological Science from the Australian Psychological Society.

Child Development and Behaviour team leaders: Professor Mark Dadds, Professor Adam Guastella, and Associate Professor David Hawes. The ParentWorks program In 2016, our team launched the Successful research grants ParentWorks program, Australia’s first

online, nationally available, evidence- Child Development and Behaviour In 2016, Professors Dadds, Guastella and Associate Professor based, father-friendly parenting program. Hawes successfully led four NHMRC Project Grant applications, Professor Mark Dadds is leading a team of attracting a total of $4,035,340 in research funding. These were: chief investigators to increase participation −− oxytocin enhancement of social learning in of fathers in parenting programs. the treatment of toddlers with autism These programs are known to be most −− mapping the specific pathways to early- effective when both parents are involved. onset mental health disorder ParentWorks is part of the ‘Like Father Like −− an integrated model of environmental, neurodevelopmental Son’ national initiative. and epigenetic resistance and responsiveness to early intervention in childhood psychopathology The program incorporates videos and homework, and features such as an −− a randomised controlled trial of oxytocin interactive child behaviour tracker that nasal spray for alcohol dependence. has been developed to improve parenting skills, confidence and child behaviour. The This team was also successful in obtaining additional online platform also incorporates a list of research grants. These include: resources available for families who require face-to-face support during or after Like Father Like Son: a national approach to violence, the program. antisocial behaviour and the mental health of men and boys Led by: Dadds, M. and Hawes, D. To find out more, go to: Granting body: Movember Foundation Award Years: 2015–17 −− www.parentworks.org.au

Amount: $2,634,400 Highlights Partnering with Cerebral Transgenerational cycles of violence model in Timor-Leste Palsy Alliance Led by: Silove, D., Rees, S., Steel, Z., Tol, W., Eapen, V. and Dadds, M. The Cerebral Palsy Alliance research Granting body: NHMRC Project Grant program aims to prevent and cure Years: 2015–19 cerebral palsy as well as find innovative Amount: $843,495 new treatments and interventions. Their researchers work across disciplines The role of oxytocin in attachment patterns and to conduct cutting edge research and socio-emotional development translate research findings into practice. Led by: Eapen, V., Silove, D., Dadds, M., Barnett, B. In 2015, this research institute formed an and Kohlhoff, J. affiliation with the University of Sydney’s Granting body: ARC Linkage Grant Brain and Mind Centre. Years: 2016–19 Amount: $192,000 Page 11 Child Development and Behaviour Key projects and clinical trials

Key research projects Clinical trials sydney.edu.au/brain-mind Understanding influence of nasal oxytocin E-health behavioural family interaction agonists on the human brain program for treatment of conduct About: This study uses brain imaging problems in children technology to track exactly where oxytocin Australian Clinical trials registry number: is delivered to the human brain via ACTRN12612000191897 nasal spray. Collaborators: NHMRC and Royal Far West Collaborators: Australian Nuclear Science Contact: Professor Mark Dadds Technology Organisation, Pastorus and Curve Technology. The efficacy of emotional engagement Funding: ARC Linkage treatment in reducing disruptive behaviour in children with oppositional defiant A longer acting oxytocin agonist targeting disorder or conduct disorder with melanocortin pathways to improve social callous-unemotional traits cognition in autism Australian Clinical trials registry number: About: This is the first study in the world to ACTRN12612000155897 apply a new melanocortin drug which acts Collaborators: Nil as a potent oxytocin agonist to treat social Contact: Professor Mark Dadds impairments in autism. Collaborators: Simons Foundation

Brain and Mind Centre Annual Report 2015-16 (New York) and Palatin Technology. Funding: Simons Foundation (New York)

Immune markers of social development in autism About: This program of research is gradually demonstrating key immune profile links with autism symptoms in the hope of developing an understanding of potential causes and treatments for autism in early development. Collaborators: Westmead Children’s Hospital and Telethon Kids Institute. Funding: Internal The University of Sydney Page 12 Child Development and Behaviour 2017 and beyond

We strive to become a major centre for Over the next 18 months we also plan to innovation in child mental health. To develop a number of innovative clinical this end, we plan to bring together our trials that target mental ill-health in young expertise in autism and child behaviour children. Collaborating with University of under one roof, to create a transdiagnostic Sydney, Westmead Children’s Hospital, clinical service and research hub. This Royal Far West and local health districts new child facility will provide a research is central to making this happen and platform that is both neurobiologically and we look forward to establishing these clinically informed. In turn, this will help us strategic partnerships. develop personalised approaches to assess Child Development and Behaviour and treat children in need. Developing a national program to disseminate our treatment strategies is also central to our goals. As is contributing these learnings to influence government policy. 2017 and beyond Page 13 Child Development and Behaviour Key publications

1. Piotrowska, P., Tully, L., 5. Kirkman, J.J.L., Hawes, D.J. 8. Dadds, M.R., Moul, C.,

sydney.edu.au/brain-mind Lenroot, R., Kimonis, E., and Dadds, M.R. (in press). Hawes, D.J., Mendoza Diaz, Hawes, D., Moul, C., Frick, An open trial for an e-health A. and Brennan, J. (2015). P.J., Anderson, V. and Dadds, treatment for child behavior Individual differences M.R. (2016). Mothers, fathers, disorders II: Outcomes in childhood behaviour and parental systems – a and clinical implications. disorders associated with conceptual model of parental Evidence-Based Practice in epigenetic modulation of the engagement in programs for Child and Adolescent Mental cortisol receptor gene. Child child mental health: Connect, Health, 1(4), 213-229. Development, 86, 1311-1320. Attend, Participate, Enact (CAPE). Clinical Child and 6. Moul, C.M., Dobson-Stone, C., 9. Moul, C., Cauchi, A., Hawes, Family Psychology Review, 1-16. Brennan, J., Hawes, D.J. and D.J., Brennan, J. and Dadds, Dadds, M.R. (2015). Serotonin M.R. (2015). Differentiating 2. Mehta, D., Eapen, V., Kohlhoff, 1B Receptor Gene (HTR1B) autism spectrum disorder and J., Mendoza Diaz, A., Barnett, Methylation as a Risk Factor overlapping psychopathology B., Silove, D. and Dadds, M. for Callous-Unemotional Traits with a brief version of the (2016). Genetic regulation of in Antisocial Boys. PLoS ONE, social responsiveness scale. maternal oxytocin response 10(5), e0126903. Child Psychiatry and Human and its influences on maternal Development, 46, 108-117. behaviour. Neural Plasticity, 7. Moul, C., Hawes, D.J. and vol. 2016. Dadds, M.R. (2015). ‘The Moral 10. Dadds, M.R., Moul, C., Brain: Psychopathology’ Hawes, D.J., Mendoza Diaz, Brain and Mind Centre Annual Report 2015-16 3. Dadds, M.R., Schollar-Root, (pp.253-264). The Moral A. and Brennan, J. (2015). O., Lenroot, R., Moul, C. and Brain: A Multidisciplinary Individual Differences Hawes, D.J. (2016). Epigenetic Perspective. In Decety J and in Childhood Behaviour regulation of the DRD4 gene Wheatley T (Eds). Boston: MIT Disorders Associated With and dimensions of Attention Press. ISBN: 978-026232758- Epigenetic Modulation of the Deficit Hyperactivity Disorder 9;978-026202871-4 Cortisol Receptor Gene. Child in children. European Child Development, 86, 1311-1320. Adolescent Psychiatry, 25, 1081-1089. OPEN Effect of oxytocin nasal spray in young children with autism Molecular Psychiatry (2016) 21, 1225–1231 CJ Yatawara et al www.nature.com/mp 1227

4. Dadds, M.R., Gale, N., ORIGINAL ARTICLE The effect of oxytocin nasal spray on social interaction deﬁcits Godbee, M., Moul, C., observed in young children with autism: a randomized clinical crossover trial Pasalich, D.S., Fink, E. and CJ Yatawara1, SL Einfeld2,3, IB Hickie2, TA Davenport2 and AJ Guastella1

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater Hawes, D.J. (2016). Expression extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double- blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social and regulation of attachment- responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits. related emotions in children Molecular Psychiatry (2016) 21, 1225–1231; doi:10.1038/mp.2015.162; published online 27 October 2015

with conduct problems and INTRODUCTION oxytocin has been found to improve face processing, decisions in 18 Autism represents a group of complex brain developmental a social ball tossing game and emotion recognition in male 19 disorders characterized by impairments in social interaction, social adults. More recently, youth with autism (aged 12–19 years) communication and stereotypical and repetitive behaviors.1 The have shown improved emotion recognition under oxytocin 2 20 The University of Sydney callous-unemotional traits. diagnosed incidence of autism is estimated to be 1 in 68 children. (18 IU). However, effective interventions have remained limited. Past research indicates that interventions for autism provided in Some psychotropic drugs, such as risperidone, seem to alleviate the early years of life offer the best opportunity to improve long- 14,21,22 behavioral problems but they are often associated with adverse term outcomes. Younger children appear to show greater events.3 There is also little evidence for effective pharmacotherapy response to intervention as observed by improved functioning Child Psychiatry and Human to alleviate core social diagnostic features.4 Alternatively, and decreases in challenging behaviors.21 The present study behavioral interventions significantly improve impairments,5 but investigated the efficacy, tolerability and safety of intranasal- they are typically time-consuming and costly.6,7 administered oxytocin to improve social interaction deficits The hormone oxytocin has been identified as having an observed by caregivers of young children with autism. Development, 47, 647-656. important role in social cognition and behavior.8 Oxytocin administration has been shown to enhance peer recognition, and bonding behavior in studies across numerous mammalian species.9 In neurotypical adult humans, intranasal administration MATERIALS AND METHODS of 24 International Units (IU) of oxytocin has been found to Study design improve eye gaze,10 emotion recognition11,12 and trust.13 This has This study of intranasal-administered oxytocin in young children with autism was a double-blind, randomized, placebo-controlled, crossover, Figure 1. Consort diagram of study participants by randomization schedule. Parents of 64 children initially contacted the Brain and Mind led to speculation for its potential application in the treatment of Centre (BMC) to enquire about the study, of which 44 children were screened for eligibility. Thirty-nine children entered the randomization fi 9,14 clinical trial. Participants were randomly allocated to study arms, where psychiatric disorders characterized by social dif culties. In schedule, and 32 (82%) completed phase 1 and then crossed-over to phase 2. One participant was excluded before completion of phase 2 each one consisted of two consecutive treatment conditions. Treatment adults with autism, initial studies evaluated effects of a single dose because of time commitments in following the protocol. The final number of participants included in the analyses was 31, including 15 of oxytocin on acute symptoms. Intravenous administration was was administered in this study using the AB/BA model. Participants who randomized to ‘oxytocin then placebo’ and 16 to ‘placebo then oxytocin’. were randomly allocated to the AB arm received oxytocin during phase 1 found to reduce repetitive behaviors15 and improve accuracy of 16 of treatment and then placebo during phase 2 of treatment. Those recognizing emotion from speech. Intranasal administration has participants who were randomly allocated to the BA arm received placebo been the preferred route of administration owing to it being well during phase 1 of treatment and then oxytocin during phase 2 of Clinical changes were also evaluated for individual participants using the RESULTS tolerated and easy to use (for dosing regimens, absorption treatment. This consequently allowed for the response of a participant to 34 pathways and bioavailability discussion of nasal administration oxytocin to be directly contrasted with their response to placebo, thus Reliable Change Index (RCI), which takes into consideration scale Participants and baseline characteristics 17 reliability of measures used. RCI is equal to an individual’s score see review in Guastella et al. ). Intranasal administration of reducing the influence of any confounding covariates. before intervention minus their score after an intervention, divided by The caregivers of 64 children initially contacted the BMC to the standard error of the difference of the measure.34 If RCI is 1.96 or enquire about the study, of which a total of 44 children were greater, then the difference is significant. If it is 1.96, RCI is not 1Autism Clinic for Translational Research, Brain and Mind Centre, Central Clinical School, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia; 2Brain and Mind o screened for eligibility. Thirty-nine of these children entered the significant. Centre, Central Clinical School, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia and 3Centre for Disability Research and Policy, Brain and Mind Centre, randomization schedule and 32 (82%) completed phase 1 and Finally, experimenter-rated CGI-I scores and caregiver-rated adverse University of Sydney, Sydney, NSW, Australia. Correspondence: Dr AJ Guastella, Autism Clinic for Translational Research, Brain and Mind Centre, The University of Sydney, Building events and impressions of treatment allocation were evaluated using then crossed-over to phase 2. One participant was excluded F, 94 Mallett Street, Camperdown, Sydney, NSW 2050, Australia. McNemar’s χ2 test for paired categorical data. For all analyses, the level of before completion of phase 2 because of competing time E-mail: [email protected] significance was set at Po0.05. commitments. The final number of participants included in the Received 28 November 2014; revised 19 August 2015; accepted 17 September 2015; published online 27 October 2015

Molecular Psychiatry (2016), 1225 – 1231 Page 14 Patient spotlight Hayden’s story

Hayden was diagnosed with Autism Spectrum Disorder when he was two years old. For much of his life, he has been trapped in his own world and unable to communicate. His mum Christine spent years trying behavioural and speech therapy, special diets and an array of medications. However nothing made a difference. Christine began to accept that little could be done to help her son participate in everyday life.

“Hayden thought he was an island. He Child Development and Behaviour didn’t want to be in a group or participate, Hayden. he wouldn’t even sit down in a circle. Everyone thought he was either strange or naughty,” explains Christine. Hayden’s engagement and communication with his family and peers continues to Therapy was slow and painful. Christine felt improve. And Christine is learning more like it was getting nowhere. “Even a small about her son every day. “I had no idea that transition or change in activity would result Hayden was aware of his surroundings until in a tantrum. He didn’t trust me or anyone he started saying things like, ‘Oh, I like that trying to help him.” car,’” says Christine. “When he said, ‘I hate you,’ for the first time I popped champagne Christine took it upon herself to research because it was the first time he was able to autism and find information on the latest express his emotions in context.” treatments. After contacting multiple paediatricians, she was directed to the This Brain and Mind Centre treatment has Brain and Mind Centre. It was there she was enabled Hayden to make friends, sit quietly told about a new trial for autistic children. and learn new things at school. He reaches It seemed manageable for Christine and new milestones all the time and often was tailored to her son’s individual needs. surprises the people around him. Recently he was even able to go on camp by himself This Brain and Mind Centre trial was a for three nights. turning point in Hayden’s life. Oxytocin was the focus of the study and he responded “The changes I saw from the trial very well to it. completely changed the way that Hayden engaged. He wanted to be a part of a group, “It was the first time Hayden was really able he didn’t fight and his language and social to engage and became aware that he was skills improved,” says Christine. not the only person in the room,” explains Christine. “Now when he knocks things over he says, ‘oops,’ and fixes it, whereas before he had tunnel vision and wouldn’t have “The changes I saw from the trial even noticed.” completely changed the way that Hayden engaged.”

Christine Mother of Brain and Mind Centre patient Hayden. Page 15 Research spotlight Dr Laura Ospinas, psychiatrist, youth mental health

Dr Laura Ospinas, a youth mental health As a psychiatrist working in youth mental psychiatrist from Colombia, is undertaking health, Laura says it’s rewarding to see how her PhD with researchers at Brain and Mind her team’s efforts can have a real impact on Centre. She was awarded the scholarship patient outcomes in terms of functionally for PhD studies abroad from the Colombian and social engagement. sydney.edu.au/brain-mind Department of Science, Technology and Innovation (COLCIENCIAS), the most “Being here, in this wonderful country, competitive scholarship for higher degree in one of the best universities in the students in Colombia. world, and working with my team at the Centre, has opened my mind. I came as a “Being awarded this scholarship is a real psychiatrist interested in research; now I source of pride. It is not only an honour, understand how research can have a real but also a great responsibility, coming impact in society and on policy, not just from a country with only a few female locally but internationally and I want to be doctorates,” says Laura. part of it.”

Laura’s research aims to understand how technology can improve young people’s health and wellbeing, both in Australia and internationally. “A big component of my research is developing, translating and culturally adapting these technological solutions into Spanish, the world’s second most spoken language,” she says. “I strongly believe that technology can help reduce Brain and Mind Centre Annual Report 2015-16 the barriers to accessing mental healthcare in migrant populations as well as in the developing world.”

Dr Laura Ospinas.

Dr Laura Ospinas Psychiatrist, youth mental health The University of Sydney

“I strongly believe that technology can help reduce the barriers to accessing mental healthcare in migrant populations as well as in the developing world.” Page 16 Youth Mental Health _

Transforming the mental health care of young people. Youth Mental Health Page 17 Youth Mental Health Our core business

The Youth Mental Health team puts young people at the centre of their own care. We partner with health services to develop innovative treatments for young people aged sydney.edu.au/brain-mind 12 to 30 years with emerging mental health disorders.

Collaboration for A new way forward Novel interventions better outcomes We aim to transform how clinical We commenced the Brain and headspace is the national care is delivered to young people Mind Youth Cohort Study in 2008. youth mental health foundation with mental health issues. Rather Nearly 10 years later, we have providing early intervention and than rely on broad diagnostic assessed 8000 individuals with mental health services to people generalisations, we want to see early phases of anxiety, mood or aged 12 to 25 years. Our research clinicians diagnose and treat psychotic disorders. From this program is heavily integrated with young people in a way that cohort we have been able to headspace Camperdown. caters to the individual needs of carry out specific clinical trials each person. of new behavioural, social and The integration of cutting-edge pharmacological interventions for research with safe and effective We focus on three main streams these disorders. clinical care enables us to quickly Brain and Mind Centre Annual Report 2015-16 of research: and effectively translate our −− neurobiological: ongoing Current studies include the youth research findings into clinical longitudinal patient studies depression alleviation trial of fish services, facilitating continuous that allow us to develop and oil (YoDA-F) and oxytocin nasal improvements to mental health trial new interventions for spray for alcohol dependence. services for the benefit of young complex mental health issues people in Australia. −− technology: optimising online environments to deliver services, track progress and provide feedback to young people and their clinicians −− clinical: continuously improving health services for young people by systematically evaluating services. The University of Sydney Page 18 headspace Camperdown clinic at Brain and Mind Centre.

International networks Youth Mental Health Brain and Mind Centre’s Youth Mental Health team is one of only three Australian groups to be actively involved in the Motor Activity Research Consortium for Health (MARCH), an international research collaboration to investigate associations between motor activity, mood and related disorders. There are research sites in the USA, Australia, Netherlands, Switzerland, China, Costa Rica, Norway and the UK, all of which are coordinated by the Genetic Epidemiology Research Branch at the National Institute of Mental Health (NIMH) in the United States. General mental health Our broad program of Similarly, we are part of the research includes: Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Our core business Consortium, a collaborative −− development of novel network of researchers from suicide prevention strategies around the globe, working −− assessment of neurobiological together on a range of large-scale markers of disease using studies that integrate data from 70 magnetic resonance institutions worldwide. Organised spectroscopy into working groups that tackle −− behavioural approaches questions on neuroscience, to the sleep-wake cycle genetics and medicine, and activity modulation ENIGMA studies have analysed −− personalised approaches neuroimaging data from more to education and than 12,826 subjects. employment participation. Page 19 Youth Mental Health Highlights

Federal government sydney.edu.au/brain-mind commits $30 million to Welcome Professor Markus Leweke, Project Synergy our new Chair of Youth Depression Studies Prime Minister Malcolm Turnbull At the end of 2016, the University Professor Leweke’s research visited Brain and Mind Centre of Sydney appointed Professor provides an alternative to in June 2016 and announced his Markus Leweke as Brain and traditional diagnostic categories commitment to invest $30 million Mind Centre’s Chair of Youth in mental illness. Rather than in Project Synergy over three Depression Studies. Professor symptoms-focused treatment, years (2017–20), as part of his Leweke plans to set up an Professor Leweke hopes to government’s $192 million mental innovative clinical service model uncover the neurobiological health policy. at the Marie Bashir Centre, a factors that underpin a range of purpose built facility designed to psychiatric conditions by working Co-developed by Brain and help people with mental health with integrated inpatient and Mind Centre and Young and Well issues. The service will assess and outpatient facilities. Cooperative Research Centre, monitor patients that present Project Synergy provides young with psychiatric problems over people at risk of suicide with fast an extended period. The primary access to mental health experts goal is to uncover the underlying via apps and online tools. causes of psychiatric illness.

Brain and Mind Centre Annual Report 2015-16 University of Sydney evaluations of Project Synergy trials in Broken Hill, NSW Central Coast and Western Sydney have shown the system effectively identifies young people at risk of suicide and helps them access urgent care from local services such as headspace and Lifeline. The University of Sydney

Professor Markus Leweke, our new Chair of Youth Depression Studies. Page 20 Psychology Clinics join Brain and Mind Centre Research grants awarded In December 2016, Australia’s Optimising early interventions for Ketamine therapy first School of Psychology moved young people with emerging mood among patients with its expanded clinics to Brain disorders (Optymise) treatment-resistant depression and Mind Centre. Mental health Led by: Hickie, I., McGorry, Led by: Loo, C., Mitchell, P., research, teaching and community P., Christensen, H., Berk, M., Glue, P., Fitzgerald, P., Glozier, clinics, including counselling, Naismith, S., Glozier, N., Burns, N., Lapidus, K., Hadzi-Pavlovic, psychiatry and neuroscience are J., Guastella, A., Davey, C., D., Somogyi, A., Hackett, M., now located in the same space. Amminger, P. Galvez, V., Rodgers, A. and This co-location of services allows Granting body: the National Mihalopoulos, C. for the provision of best practice Health and Medical Research Granting body: NHMRC and cost effective brain and mind Council (NHMRC) Centres of Project Grant services to the community. Research Excellence (CREs) Years: 2016–18 Years: 2014–18 Amount: $606,094 Gambling Treatment and Amount: $2,499,420 Men@Work Research Clinic joins Brain Bridging the gap from the Led by: Harvey, S., Christensen, and Mind Centre cradle to the mosh pit H., Proudfoot, J., Mitchell, P., Youth Mental Health The Gambling Treatment and Led by: Jones, C., Scott, S., Cockayne, N., Santamaria, J., Research Clinic, which sees Dale, R., Banati, R., Booy, R., Bryant, R., Glozier, N., Hickie, I., more than 600 patients per Lagapoulos, J., Barnett, M., Buchanan, J., Ryan, R., Calvo, R., year, received a generous $1.2 Hill-Cawthorne, G., Hermens, D., Bohle, P., Salvador-Carulla, L. and million deed of gift by ClubsNSW Khandaker, G. Fernandez Sanchez, A. over three years (2013–16). This Granting body: the Health & Granting body: beyondblue led to the appointment of two Medical Research Strategy research grant doctoral students to carry out a SPARC Implementation Fund (the Years: 2015–18 retrospective and prospective University of Sydney) Amount: $181,000 evaluation of several programs. Years: 2015–16 These include: an innovative multi- Amount: $50,000 venue self-exclusion program, a joint chaplaincy program with the Salvation Army implemented within clubs, and defining and measuring recovery in gambling.

In 2016, the Clinic’s Director, Professor Alexander Blaszczynski, was appointed President of the NSW Psychology Council. Dr Sally Gainsbury also became the Highlights Clinic’s new Deputy Director and received an Australian Research Council Discovery Early-Career Researcher Award (DECRA) to explore the influence of features of the online environment on risk taking.

Gambling Treatment and Research Clinic. Page 21 Youth Mental Health 2017 and beyond

Professor Jane Burns to lead InnoWell sydney.edu.au/brain-mind InnoWell is an innovative company Brain and Mind Centre’s role is to ensure bringing digital mental health solutions the research is of the highest possible to the people who need them. The standard. As well as to enable access first of its kind in the world, InnoWell to service users who can both test the brings together the academic rigour of platform and provide feedback as part of Brain and Mind Centre’s mental health the research and development process. expertise and the corporate influence of PricewaterhouseCoopers (PwC). The project is a truly joint partnership. Thanks to its corporate backing, there InnoWell is one of the University of is a clear route to taking the product to Sydney’s largest collaborations with a major scale, with PwC able to expand the project corporate backer, leading the way for to a mass market. Mental health issues proven research to translate into real- have a clear impact on the economy. By world outcomes. addressing them, we can attain both a social and financial return on investment. InnoWell plans to conduct twelve research trials over four years. In its first year, young people, veterans, post-hospital discharge patients and older Australians will use

Brain and Mind Centre Annual Report 2015-16 Project Synergy software to track their mental health. Researchers will monitor their engagement with the program and its effectiveness. The University of Sydney

Professor Jane Burns (top left) and the Youth Mental Health team. Page 22 Youth Mental Health Key projects and clinical trials

Key research projects A new clinical staging model for health. It uses data collected and effective long-term personalised and responsive care through digital technologies to interventions. The package We have successfully developed promote help-seeking behaviours of tools is referred to as the a new clinical staging model to and, if necessary, facilitate clinical Brain and Mind Youth Platform help clinicians accurately identify care and engagement with online and is supported by the Future the severity of illness in a young and face-to-face clinical services. Generation Global Investment person. With this knowledge, Company (FGG). options for safer and more Early success – trialling Project Youth Mental Health effective interventions can be Synergy in Sydney Subscription to the Platform discussed between the young We have successfully trialled the allows access to the same level person and their treating team, in Synergy platform in five headspace of detailed clinical assessment line with the stage of illness the centres across Central and and tracking techniques as those young person has. Eastern Sydney Primary Health currently available only at Brain Network (CESPHN). Young people and Mind Centre. This access This approach will help completed a comprehensive to specialist care gives young healthcare providers deliver online assessment before entering people the greatest opportunity better quality services. As well as headspace and Synergy allowed of achieving recovery from clinical assist clinicians to consider the young people and services to depression. potential trajectory of an illness to see the same health summary better guide support, intervention information. This resulted in faster Wellbeing@Work and service design. It has been detection of suicide risk, quicker Led by Professor Nick Glozier implemented in a number of access to care, and more accurate from Brain and Mind Centre and headspace services across treatment planning and allocation researchers at the University of the country. of clinical care resources to match New South Wales, the Wellbeing@ the needs of the young person. Work project, funded by Project Synergy – transforming beyondblue, examines how we healthcare services Through a participatory design can use technology to improve We are using new online process, clinicians also identified wellbeing in the workforce. technologies to develop highly clinical education needs, To do this, we have developed

specialised programs for people resulting in training workshops algorithms to assess mental health Key projects and clinical trials with mental health problems. being conducted by researchers risk, created online manager Together with the Young and Well to improve service quality training resources, and built a Cooperative Research Centre and consistency. 30 day mental health and and supported by the federal wellbeing prevention program. Department of Health, we have Brain and Mind Youth Platform developed Project Synergy; We are developing novel clinical The project has involved an innovative e-mental health assessment and longitudinal thousands of participants from ecosystem of care for young tracking tools using new and workplaces including Australia people. This incorporates a emerging technologies to detail Post, Fortescue Mining, Dairy range of complementary apps psychological, cognitive, social Farmers and more. and web-based interventions to and medical characteristics of manage wellbeing and mental depression and plan individualised Page 23 Clinical trials Longitudinal Twin Study The Fish Oil Youth Ketamine therapy We are leading a large, long-term Depression Study among patients with prospective study of adolescent This team established and treatment-resistant depression twins. The project, titled Can We conducted the first two sites of In 2016, researchers from Brain Predict Who Will Develop Major The Fish Oil Youth Depression and Mind Centre commenced Mental Disorders: A Long-term Study: a Randomised, Double work on a randomised, double- Study of Adolescent Twins, funded Blind, Placebo-Controlled blind, placebo-controlled trial by the NHMRC, tracks real-time Treatment Trial. The NHMRC- of ketamine therapy among developmental trajectories of funded randomised controlled patients with treatment-resistant the onset of anxiety and mood, trial of omega-3 fish oil in young depression. Funded by an NHMRC sydney.edu.au/brain-mind psychotic, or substance misuse people with major depression ran project grant, this is the first study disorders through adolescence at headspace Camperdown and of its kind in the world. and young adulthood. Now at the headspace Campbelltown. 20-year reassessment mark, the In October 2016, the ketamine study will determine the extent to In December 2016, we completed trial was launched at the Marie which neurobiological and genetic data collection on 95 patients. Bashir Centre, the first time Brain markers can predict outcomes, The trial is ongoing until 2018 and and Mind Centre research was to help inform the development will run at four other sites in Perth carried out in conjunction with of novel prevention or early and Melbourne. Sydney Local Health District. The intervention strategies. study will trial repeated doses Collaborators: Professors Paul and monitor safety, side effects Amminger, Pat McGorry, Alison and implementation issues before Yung, Andrew Mackinnon, Michael treatment is offered to the Berk and Assistant Professor wider population. Chris Davey. Collaborators: Brain and Mind Centre, UNSW, Monash University, University of Western Sydney (UWS), University of

Brain and Mind Centre Annual Report 2015-16 South Australia (UniSA) and Alfred Health. The University of Sydney

The Professor Marie

Page 24 Bashir Centre. Youth Mental Health Key publications

1. O’Dea, B., Glozier, N., Purcell, 5. McGorry, P.D., Goldstone, 9. Scott, E.M., Hermens, D.F., R., McGorry, P., Scott, J., S.D., Parker, A.G., Rickwood, White, D., Naismith, S.L., Fields, K., Hermens, D., D.J. and Hickie, I.B. (2014). Gehue, J., Whitwell, Glozier, Buchanan, J., Scott, E., Yung, Cultures of mental health N. and Hickie, I.B. (2015). Body A., Guastella, A., Hickie, I., et care of young people: an mass, cardiovascular risk and al. (2014). A cross-sectional Australian blueprint for metabolic characteristics of exploration of the clinical reform. Lancet Psychiatry, young persons presenting characteristics of disengaged Dec 1(7): 559-68. doi: 10.1016/ for mental health care in young people in primary S2215-0366(14)00082-0. Sydney, Australia. BMJ Open, mental healthcare. BMJ Open, Epub 2014 Dec 3. Review. 5: e007066. 4(12), 1-8. PMID: 26361315. 10. Lee, R.S.C., Hermens, D.F., Youth Mental Health 2. Scott, J., Murray, G., Henry, 6. McGorry, P., Keshaven, M., Naismith, S.L., Lagopoulos, C., Morken, G., Scott, E., Goldstone, S., Amminger, P., J., Jones, A., Scott, J., Chitty, Angst, J., Merikangas, K.R. Allott, K., Berk, M., Lavoie, K.M., White, D., Robillard, R., and Hickie, I.B. (2017). S., Pantelis, C., Yung, A., Scott, E.M. and Hickie, I.B. Activation in bipolar Wood, S. and Hickie, I.B. (2015). Neuropsychological disorders: a systematic (2014). Biomarkers and clinical and functional outcomes review. JAMA Psychiatry, Feb staging in psychiatry. World in recent-onset major 1; 74(2): 189-196. doi: 10.1001/ Psychiatry, Oct; 13(3):211-23. depression, bipolar disorder jamapsychiatry.2016.3469. doi: 10.1002/wps.20144 PMID: and schizophrenia-spectrum PMID: 28002572. 25273285. disorders: a longitudinal cohort study. Translational 3. Long, E.C., Verhulst, B., 7. Robillard, R., Hermens, D.F., Psychiatry, 5: e555. Neale, M.C., Lind, P.A., Naismith, S.L., Rogers, N.L., Hickie, I.B., Martin, N.G. and Ip T.K, White, D., Mullin, S.J., Gillespie, N.A. (2016). The Alvares, G.A., Guastella, A.J., genetic and environmental Smith, K.L., Rong, Y., Scott, contributions to internet E.M. and Hickie, I.B. (2015). use and associations with Ambulatory sleep-wake psychopathology: a twin patterns and variability in study. Twin Research and young people with emerging Human Genetics, Feb; 19(1): mental disorders. Journal of 1-9. doi: 10.1017/thg.2015.91. Psychiatry & Neuroscience,

Epub 2015 Dec 23. PMID: 40: 28-37. Key publications 26693596. Also see: https:// genepi.qimr.edu.au/ 8. Chitty, K.M., Lagopoulos, J., contents/p/staff/Gillespie_ Hickie, I.B. and Hermens, TRHG16_1_21-33.pdf D.F. (2015). A longitudinal proton magnetic resonance 4. Burns, J.M., Birrell, E., spectroscopy study Bismark, M., Pirkis, J., investigating oxidative stress Daventport, T.A., Hickie, I.B., as a result of alcohol and Weinberg, M.K. and Ellis, L.A. tobacco use in youth with (2016). The role of technology bipolar disorder. Journal in Australian youth mental of Affective Disorders, 175: health reform. Australia Health 481–87. Review, Mar 3. doi: 10.1071/ AH15115. PMID: 26934382.

Professor Nick Glozier Page 25 11. Carpenter, J.S., Robillard, 13. Gehue, J., Scott, E., 15. Iorfino, F., Hickie, I.B., Lee, R., Lee, R.S.C., Hermens, Hermens, D., Scott, J. and R.S.C., Lagopoulos, J. and D.F., Naismith, S.L., White, Hickie, I. (2015). Youth Early Hermens, D.F. (2016). The D., Whitwell, B., Scott, E.M. Intervention Study (YES): a underlying neurobiology of key and Hickie, I.B. (2015). The randomised controlled trial functional domains in young relationship between sleep- investigating the efficacy of people with mood and anxiety wake cycle and cognitive group interventions targeting disorders: a systematic review. functioning in young people social participation838 and BMC Psychiatry, 16: 156. D.F. Hermens et al.

with affective disorders. PLoS physical wellbeing2. Experimentalas an procedures degree family history) of any mental health problems. The social one, 10: e0124710. adjunct to usual treatments 16. O’Dea, B., Lee, R.S.C., and occupational functioning assessment scale (SOFAS) was utilized Young adult (18 to 30 yrs old) outpatientsMcGorry, were P.D., recruited Hickie, from I.B.,as a measure of current overall psychosocial functioning. To offered by youthspecialized mental services for the assessment and early intervention of mental quantify general psychiatric, mood and manic symptoms the inter- 12. Hermens, D.F., Naismith, health problems (Hermens et al., 2011Scott,, 2012 ).J., All Hermens, patients had a D.F.,view included the: (i) Brief Psychiatric Rating Scale (BPRS, 24- sydney.edu.au/brain-mind health services.primary Trials diagnosis, 16: of333. a mood (i.e. depressive or bipolar) disorder as item); (ii) Hamilton Depression Rating Scale (HDRS, 17-item); and S.L., Chitty, K.M., Lee, determined by a psychiatrist, accordingMykletun, to DSM-IV criteria A., andPurcell, under- R.,(iii) Young Mania Rating Scale (YMRS). Mood state was determined went a clinical/neuropsychological assessment and magnetic resonance based on an algorithm using patients' HDRS and YMRS scores (see R.S.C., Tickell, A., Duffy, 14. Cross, S.P., Hermens,imaging (MRI) D.F. within a 3-month period.Killackey, Primary diagnoses E., Pantelis, were as C.,Supplementary material for more details). S.L., Paquola, C., White, D., and Hickie, I.B.follows: (2016). (i) n =90 had a depressiveAmminger, (‘unipolar’) disorder G.P. [i.e. and major Glozier,All participants N. were also asked to complete the Kessler-10 (K-10), depressive (n=53); depression with atypical features (n=2); dysthymic which is a brief self-report instrument to detect psychological distress. Hickie I.B. and Lagopoulos, I. Treatment patterns(n=5); depressionand with psychotic features(2016). (n =A3); prospective depression not cohortParticipants were asked about their lifetime and current substance use otherwise specified (NOS) (n=27)]; and (ii) n=75 had a ‘bipolar’ using the first two items of the World Health Organization's ‘Alcohol, (2015). Cluster analysis reveals short-term outcomesdisorder [i.e. in bipolar an I (BD-I; n=24);study bipolar II of (BD-II; depressionn=26); bipolar course,Smoking and Substance Involvement Screening Test’. The Alcohol Use fi abnormal hippocampal early-interventiondisorder youth NOS (BD-NOS; n=25)]. Patientsfunctional were assessed disability, under ‘treat- andDisorders NEET Identi cation Test (AUDIT) was used to assess a participant's ment as usual’ conditions; at the time of assessment, 22.2% were not level of risky drinking in the past year, as well their lifetime familiarity. neurometabolic profiles mental health service.taking any psychotropicEarly medications;status 57.6% werein help-seeking taking an anti- young depressant, 31.6% an atypical antipsychotic medication and 32.3% were in young people with Intervention in takingPsychiatry a mood stabilizer., 10: adults. Social Psychiatry2.2. and Neuropsychological assessment mood disorders. European 88–97. Healthy controls (n=40; 19 to 30Psychiatric yrs) were recruited Epidemiology from the , 51: community in the same metropolitan geographic area as the out- Premorbid IQ was estimated on the basis of performance on the Neuropsychopharmacology, patients. A research psychologist1395–404. screened the participants via Wechsler Test of Adult Reading. As this study focuses on neurome- clinical interview for psychopathology to ensure that they did not tabolites measured within the hippocampus we specifically assessed 25, 836–845. have a history of a mental or substance use disorder. For all ‘verbal learning and memory’ via the Rey Auditory Verbal Learning subjects, exclusion criteria included: history of significant neurolo- Test (RAVLT) using the sum of trials RAVLT A1-A5 (learning) and 20- gical disease, medical illness known to impact cognitive and brain min delayed recall by RAVLT A7 (memory). As a means of determin- function, intellectual and/or developmental disability (premorbid ing the specificity of cognitive findings we also assessed ‘psycho- intelligence (IQ)o70), current substance dependence and insuffi- motor speed’ via the Trail-Making Test, part A (TMT A) and ‘mental cient English for assessment. The University of Sydney Human flexibility’, assessed by part B (TMT B). Research Ethics Committee approved the study and all participants gave informed consent. 2.3. 1H MRS scans European Neuropsychopharmacology (2015) 25, 836–845 2.1. Clinical assessment 1H MRS data was acquired on a 3 T GE Discovery MR750 MRI scanner (GE Medical Systems, Milwaukee, WI), using an 8-channel phased array head A research psychologist conducted a semi-structured interview to coil. The protocol comprised of a three-dimensional sagittal whole-brain determine the nature and history (including first- and second- scout for orientation and positioning of all scans (TR=50 ms; TE=4 ms; matrix=256; no averaging, z=5 mm thickness). To aid in the anatomical www.elsevier.com/locate/euroneuro

Brain and Mind Centre Annual Report 2015-16 localization of sampled voxels, a T1-weighted Magnetization Prepared Rapid Gradient-Echo (MPRAGE) sequence producing 196 sagittal slices (TR=7.2 ms; TE=2.8 ms; flip angle=101; matrix 256 256; .9 mm Â Cluster analysis reveals abnormal isotropic voxels) was also acquired. Finally, single voxel 1H MRS using hippocampal neurometabolic profiles a Point RESolved Spectroscopy (PRESS) acquisition with two chemical in young people with mood disorders shift-selective imaging pulses for water suppression was acquired from a 1.5 3.0 1.0 cm3 voxel placed in the left hippocampus (TE=35 ms, Â Â TR=2000 ms, 128 averages voxel size 4.5 cm3). Anatomical localization Daniel F. Hermensn, Sharon L. Naismith, Kate M. Chitty, of voxel placement was based on the Talairach brain atlas and Rico S.C. Lee, Ashleigh Tickell, Shantel L. Duffy, Casey Paquola, Django White, Ian B. Hickie, Jim Lagopoulos positioning was guided by the T1 MPRAGE image (see Figure 1). All spectra were shimmed to achieve full-width half-maximum (FWHM) of o13 Hz. Prior to any post-processing all spectra were visually Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Australia inspected, separately by two independent raters, to ensure the fi Received 31 October 2014; received in revised form 10 February 2015; accepted 25 February 2015 consistency of the data. Poorly tted neurometabolite peaks as reflected by large (420) Cramer–Rao Lower Bounds (CRLB) were excluded from further analysis (see Supplementary material for more KEYWORDS Abstract details on the numbers of subjects who were not eligible for inclusion Hippocampus; While numerous studies have employed magnetic resonance spectroscopy (MRS) to determine Mood disorders; in vivo neurometabolite levels associated with mood disorders the findings in both unipolar due to ‘invalid’ MRS data). Proton magnetic reso- depression and bipolar disorder have been mixed. Data-driven studies may shed new light on nance spectroscopy; this literature by identifying distinct subgroups of patients who may benefit from different Glutamate; treatment strategies. The objective of the present study was to utilize hierarchical cluster N-acetyl aspartate; analysis in order to generate new hypotheses with respect to neurometabolic profiling of mood Myo-inositol 1 disorder. Participants were 165 young persons (18–30 yrs) with a mood disorder and 40 healthy 2.4. H MRS spectrum analysis controls. Neurometabolite levels were recorded via proton-MRS (1H MRS). The ratios (relative to creatine) of glutamate (GLU), N-acetyl aspartate (NAA) and myo-inositol (MI) measured within Figure 1 Water suppressed spectra (sampled from the hippo- the hippocampus. Self-reported and clinician rated symptoms as well as cognition were also Spectra were quantified with the LCModel software package using a campus) processed using LCModel from a single representative measured. The unipolar depression (N=90) and bipolar disorder (N=75) groups did not PRESS TE=35 basis set of 15 metabolites, incorporating macro- significantly differ (from each other or controls) in their levels of GLU, NAA or MI. Cluster subject. Abbreviations are as follows: MI=myo-inositol; analyses derived four subgroups of patients who were distinguished by all three metabolites. molecule and baseline fitting routines. Statistical analyses were There was a pattern of positive association between NAA and GLU, whereby clusters were Cr=creatine; GLU=glutamate; NAA=N-acetylaspartate. Top abnormally increased (clusters 1, 2) or normal (cluster 4) or abnormally decreased (cluster 3) in then conducted on the following metabolites: GLU, NAA, MI and Cr. these neurometabolites. These findings suggest that there are neurometabolic abnormalities in right panel: Sagittal views of representative T1-weighted All neurometabolite levels are reported as ratios to water-scaled subgroups of young people with mood disorder, which may occur despite diagnostic similarities. images illustrating the voxel placement for the hippocampus Such evidence highlights that the underlying neurobiology of mood disorder is complex and MRS creatine (Cr) concentration (see Supplementary material for more may have unique utility in delineating underlying neurobiology and targeting treatment (white box). details). strategies. &

nCorrespondence to: Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia. Tel.: +61 2 93510529; fax: +61 2 93510652. E-mail address: [email protected] (D.F. Hermens).

Ben Trist, a PhD student at Brain and Mind Since commencing with Brain and Mind Centre, is investigating the effects of Centre in 2015, Ben’s PhD candidature decreasing levels of copper in the brains of has progressed smoothly. “The Centre’s patients with Parkinson’s disease. In 2016, laboratory and administration facilities he won Parkinson’s NSW Young Researcher have enabled me to mature as a research of the Year Award. scientist,” he says. “In particular, the microscopy facilities have allowed me Ben’s interest in Parkinson’s disease partly to advance my work on human brain derives from his first-hand experience tissue pathology, owing largely to the of the disease; his grandfather suffered expertise and technical support of Dr from it. However, it also stems from the Michael Kuligowski.” influence of his supervisor, Associate Professor Kay Double, who encouraged Youth Mental Health him to pursue this fascinating area of study. “I have always had an interest in the ageing process and how this process can be determined by an individual’s genetic information, but more intriguingly, by their experiences and lifestyle,” says Ben.

“I think my award is testament to the importance of the work we as a team are carrying out, and shows that our long hours and hard work are producing results that the scientific community and general public perceive as significant,” he adds. “On a more personal level, it has given me a boost of confidence in my abilities as a researcher.”

Ben Trist, PhD student.

Ben Trist PhD student

“I have always had an interest in the ageing process and how this process can be determined by an individual’s genetic information, but more intriguingly, by their experiences and lifestyle.” Page 27 Neuroimmunology _

Developing new ways to detect and treat neurological disease. The University of Sydney Page 28 Neuroimmunology Our core business

Our neuroimmunology research focuses on improving our understanding of neurological and psychiatric diseases. It has become clear that many of them are associated with a dysregulation of the immune system. Neuroimmunology Autoantibodies are one part of the immune The integration of our basic laboratory system and are important in many nervous research, clinically applied research and system disorders. In fact, they define health service provision will enable us certain clinical syndromes. This provides to readily translate our findings into real us with an unprecedented opportunity to world applications. develop novel diagnostic biomarkers of disease and importantly, develop new and This research program stems from a innovative treatments for some of the most collaboration involving a consortium debilitating neurological diseases. of academics and clinicians from the Westmead Hospital, the Children’s Hospital Our collective expertise in autoantibody at Westmead, Westmead Institute for and other biomarker detection, exploration Medical Research, Save Sight Institute, of antibody pathogenicity, neuropathology, Bosch Institute, Royal Prince Alfred Hospital imaging and clinical service delivery puts us and Concord Hospital. at the forefront of this research.

Our focus is on identifying and investigating immune and antibody-mediated neurological diseases, including: −− demyelinating diseases such as multiple sclerosis

−− motor neurone disease Our core business −− psychiatric diseases −− movement disorders −− dementia −− myasthenia gravis and more.

Professor Fabienne Brilot-Turville, Senior

Research Fellow, Neuroimmunology team. Page 29 Neuroimmunology Highlights

The Sydney Research sydney.edu.au/brain-mind Excellence Initiative Prizes and awards Neurology training In 2016, the Neuroimmunology Professor Steve Vucic was The Australian and New Zealand team successfully applied to awarded the Royal Australasian Association of Neurologists the Sydney Research Excellence College of Physicians’ Eric (ANZAN) Neuroimaging and Initiative, a new scheme to Susman Prize and the Australian Neuropathology course is an support Sydney researchers to Academy of Science Gottschalk annual training course that has test new ideas, push disciplinary Medal for his pioneering work been conducted by Associate boundaries and identify ways to to identify mechanisms that Professors Michael Barnett and scale up research. The project, underlie motor neurone disease Michael Buckland for the past four titled Neuroimmunology and (MND). His research has assisted years. Due to its early success, the Neuroinflammation: From in the development of new course is now a compulsory part Biomarker and Pathogenesis techniques for diagnosing MND, of advanced neurology training in to Patient Diagnosis and resulting in earlier and more Australia and New Zealand. Improvement of Clinical Outcome, effective interventions. is focused on implementing a SNAC collaboration neuroimmune service across the Associate Professor Michael University’s campuses to support Barnett was awarded a Sydney Our collaboration with Sydney diagnosis and inform clinical Research Accelerator (SOAR) Neuroimaging Analysis Centre care in patients with suspected Fellowship to identify and develop (SNAC) has continued to publish

Brain and Mind Centre Annual Report 2015-16 neuroimmune disorders. The new and early biomarkers for high impact multiple sclerosis project focuses on investigating multiple sclerosis. Professor (MS) imaging biomarker research, mechanisms of neuroinflammation Barnett is a leader in multiple which translated to clinical trials by identifying and validating novel sclerosis research and has been in 2015. SNAC, in partnership biomarkers to improve long-term instrumental in developing a with industry, has sponsored clinical outcomes for patients and neuroimaging platform at Brain and co-funded a number of our their families. and Mind Centre. investigator-initiated research studies to assess clinical and The SOAR Fellowship provides neuropsychological outcomes two years of additional research of existing MS treatments. SNAC funding for Professor Barnett to also provided infrastructure and continue his work in detecting expertise to support three PhD and monitoring early signs of candidates in 2015–16. multiple sclerosis. The University of Sydney Page 30

Further MS collaborations Dr Heidi Beadnall (right) works with an MS patient. Our dedicated MS clinical trials unit works closely with our multidisciplinary MS Clinic, a 20 year collaboration with MS Limited and Royal Prince Alfred Hospital. In 2015, patients of the MS Clinic participated in more than 10 Neuroimmunology industry Phase 2 to 4 clinical trials or studies and several investigator-initiated studies.

In 2015, our MS clinicians worked with Sydney Local Health District (SLHD) and Medical Safety Systems to develop and trial an automated safety monitoring system for patients treated with alemtuzumab. In mid-2015, the resulting software platform was adopted for clinical use and has been deployed nationwide.

MS Research Australia Brain Bank, co-directed by Associate Professors Michael Barnett and Michael Buckland and funded by MS Research Australia and SLHD, provided characterised donor

MS tissue to researchers in both Highlights Australia and the United States. Page 31 Neuroimmunology 2017 and beyond

Statewide brain autoantibody 14th International Congress sydney.edu.au/brain-mind test referral centre of Neuroimmunology A key goal of the Neuroimmunology team is The International Society for to establish a statewide brain autoantibody Neuroimmunology’s 14th International test referral centre. By pooling together Congress of Neuroimmunology will take existing expertise and infrastructure place in Brisbane in August 2018. This huge from across Royal Prince Alfred Hospital, event attracts experts from across the Concord Hospital, Westmead Hospital world and will take place in the southern and Brain and Mind Centre, this collective hemisphere for the first time. Brain network of centres will provide patients, and Mind Centre’s Neuroimmunology clinicians and researchers with a one-stop- team is heavily involved in organising shop for neuroimmunology tests. this conference that will attract a large delegation of experts from across Australia and the world. Brain and Mind Centre Annual Report 2015-16 The University of Sydney

Researchers in the

Page 32 neurology laboratory. Neuroimmunology Key publications

The Neuroimmunology team was built upon an extensive body of ground-breaking research including a number of seminal papers published in the years leading up to the team’s founding in 2016.

In 2012, our researchers made a The team also published the 3. Barnett, M., Mathey, E., seminal discovery of D2R antibody largest and most influential paper Kiernan, M. and Pollard, in children with movement and on the use of rituximab in children J. (2016). Axon damage in psychiatric disorders: with brain inflammation that has central nervous system and seen 75 citations since 2014: peripheral nervous system

1. Dale, R.C., Merheb, V., inflammatory demyelinating Neuroimmunology Pillai, S., Wang, D., Cantrill, 1. Dale, R.C., Brilot, F., Duffy, diseases: common and L., and Murphy, T.K., et al. L.V., Twilt, M., Waldman, A.T. divergent pathways of (2012). Antibodies to surface and Narula, S., et al. (2014). dysfunction and tissue dopamine-2 receptor in Utility and safety of rituximab damage. Current Opinion in autoimmune movement and in pediatric autoimmune and Neurology, 29(3), 213-221. psychiatric disorders. Brain, inflammatory CNS disease. (cites 85 WoS/130 GS). Neurology, 83(2):142-50. 4. Lorscheider, J., Buzzard, K., Jokubaitis, V., Spelman, T., In 2014, the group discovered Our MS researchers and clinicians Havrdova, E., Horakova, D., a new clinical phenotype have also been published widely Trojano, M., Izquierdo, G., in myelin oligodendrocyte throughout 2015–16: Girard, M., Vucic, S., Barnett, glycoprotein (MOG) antibody M., et al. (2016). Defining in demyelinating diseases: 1. Hardy, T., Reddel, S., Barnett, secondary progressive M., Palace, J., Lucchinetti, multiple sclerosis. Brain, 1. Dale, R.C., Tantsis, E.M., C. and Weinshenker, B. 139(PT 9), 2395-2405. Merheb, V., Kumaran, (2016). Atypical inflammatory 5. Klistorner, A., Vootakuru. R.Y., Sinmaz, N. and demyelinating syndromes N., Wang. C., Yiannikas. Pathmanandavel, K., et of the CNS. The Lancet C., Graham. S.L., Parratt, al. (2014). Antibodies to Neurology, 15(9), 967-981. J., Garrick, R., Levin, N., MOG have a demyelination Masters, L., Lagopoulos, J. phenotype and affect 2. Wang, C., Beadnall, H., Hatton, and Barnett, M.H. (2015). oligodendrocyte cytoskeleton. S., Bader, G., Tomic, D., Silva, Decoding diffusivity in Key publications Neurol Neuroimmunol D. and Barnett, M. (2016). multiple sclerosis: analysis Neuroinflamm, 1(1):e12 Automated brain volumetrics of optic radiation lesional (cites 44 GS). in multiple sclerosis: a step closer to clinical application. and non-lesional white 2. Ramanathan, S., Reddel, S.W., Journal of Neurology, matter. PLoS ONE, 10(3): Henderson, A., Parratt, J., Neurosurgery and Psychiatry, e0122114. doi:10.1371/journal. Barnett, M. and Gatt, P., et al. 87(7), 754-757. pone.0122114. (2014). Antibodies to myelin oligodendrocyte glycoprotein in bilateral optic neuritis. Neurol Neuroimmunol Neuroinflamm, (cites 48 GS). Page 33 6. Klistorner, A., Wang, C., 9. Broadley, S.A., Barnett, M.H., Yiannikas, C., Graham, S.L., Boggild, M., et al. (2015). A Parratt, J. and Barnett, M.H. new era in the treatment of (2016). Progressive injury in multiple sclerosis. Med J Aust, chronic multiple sclerosis Aug 3; 203(3):139-41. lesions is gender-specific: a DTI study. PLoS One, Feb 22; 10. Wang, C., Paling, D., Hatton, 11(2):e0149245. S., Lagopoulos, J., Aw, S., Kiernan, M. and Barnett, M. 7. Barnett, M.H., McLeod, (2015). Axonal conduction in J.G., Hammond, S.R. and multiple sclerosis: a combined Kurtzke, J.F. (2016). Migration magnetic resonance imaging sydney.edu.au/brain-mind and multiple sclerosis in and electrophysiological study immigrants from United of the medial longitudinal Kingdom and Ireland to fasciculus. J Mult Scler, Jun; Australia: a reassessment. III. 21(7):905-15. Risk of multiple sclerosis in UK immigrants and Australian- born in Hobart, Tasmania. J Neurol, Apr; 263(4):792-8.

8. Beadnall, H.N., Kuppanda, K.E., O’Connell, A., Hardy, T.A., Reddel, S.W. and Barnett, M.H. (2015). Tablet- based screening improves continence management in multiple sclerosis. Ann Clin Trans Neurol, Jun; 2(6):679-87. Brain and Mind Centre Annual Report 2015-16

Antibodies to MOG have a demyelination Figure 2 Temporal distribution of MOG antibody in serum of 2 relapsing patients with demyelinating diseases phenotype and affect oligodendrocyte cytoskeleton

Russell C. Dale, PhD* ABSTRACT Esther M. Tantsis, Objective: To examine the clinical features of pediatric CNS demyelination associated with pos- MBBS* itive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects Vera Merheb, BSc of MOG antibody on oligodendrocyte cytoskeleton. Raani-Yogeeta A. Methods: We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay Kumaran, BMedSc in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3–15.3) Nese Sinmaz, BSc followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on Karrnan Pathmanandavel, oligodendrocyte cytoskeleton using 3D deconvolution imaging. MBBS Sudarshini Ramanathan, Results: MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first FRACP presentation, MOG antibody–positive patients were more likely to have bilateral than unilateral optic David R. Booth, PhD neuritis (ON) (9/10 vs 1/5, respectively, p 5 0.03), less likely to have brainstem findings (2/31 vs Louise A. Wienholt, PhD 16/42, p 5 0.005), more likely to have a raised erythrocyte sedimentation rate .20 mm/h (9/19 vs Kristina Prelog, FRACP 3/21, p 5 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p 5 0.18), and less Damien R. Clark, FRACP likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, Gilles J. Guillemin, PhD p 5 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON Chai K. Lim, PhD most likely to be seropositive. Two relapsing MOG antibody–positive patients treated with mycophe- Emily K. Mathey, PhD nolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes Fabienne Brilot, PhD incubated with purified IgG from MOG antibody–positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and b-tubulin immunolabelings. Correspondence to Conclusions: MOG antibody may define a separate demyelination syndrome, which has therapeu- Dr. Brilot: [email protected] tic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton. Neurol Neuroimmunol Neuroinflammation 2014;1:e12; doi: 10.1212/NXI.0000000000000012

GLOSSARY ADEM 5 acute disseminated encephalomyelitis; AQP4 5 aquaporin-4; CIS 5 clinically isolated syndrome; DEM 5 demyelinating diseases; ESR 5 erythrocyte sedimentation rate; FACS 5 fluorescence-activated cell sorting; HC 5 healthy control; HEK 5 human embryonic kidney; HLA 5 human leukocyte antigen; Ig 5 immunoglobulin; MBP 5 myelin basic protein; MMF 5 mycophenolate mofetil; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; ON 5 optic neuritis; SNP 5 single nucleotide polymorphism; TM 5 transverse myelitis.

Recently, autoantibodies that bind to cell surface antigens have been shown to be important diagnostic biomarkers in autoimmune brain disease, including autoimmune encephalitis and autoimmune demyelination.1–3 Myelin oligodendrocyte glycoprotein (MOG) is a minor component of myelin proteins but has been the focus of extensive research in demyelinating diseases. MOG is localized on the outermost surface of myelin and has a proposed role in the regulation Supplemental data at Neurology.org/nn *These authors contributed equally to the manuscript. In both patient A (A) and patient B (B), upon treatment mycophenolate mofetil (MMF), myelin oligodendrocyte glycoprotein (MOG) antibody decreased to From the Neuroimmunology Group (R.C.D., E.M.T., V.M., R.-Y.A.K., N.S., K. Pathmanandavel, S.R., F.B.), Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead, Sydney Medical School, University of Sydney, Westmead, within the healthy control range (below threshold of positivity), and these low titers were associated with remission. Representative dot plot out of 3 experi- Australia; Institute for Immunology and Allergy Research (D.R.B.), Westmead Millenium Institute for Medical Research, University of Sydney, Westmead, Australia; Clinical Immunology (L.A.W.), Royal Prince Alfred Hospital, Sydney Medical School Immunology & Infectious Diseases, ments is shown. Magenta lines on graphs represent the positivity threshold (obtained with 24 control samples). Black squares represent serum analysis dur- The University of Sydney University of Sydney, Camperdown, Australia; Department of Radiology (K. Prelog), the Children’s Hospital at Westmead, Australia; Department of Paediatric Neurology (D.R.C.), Women’s and Children’s Hospital, North Adelaide, Australia; Neuroinflammation Group (G.J.G., C.K.L.), ing acute demyelination episodes, and black circles represent sera during remission. Type of demyelinating episode is shown on graph. (C, D) Representative MND and Neurodegenerative Diseases Research Centre, Macquarie University, Australian School of Advanced Medicine, North Ryde, Australia; and Neuroinflammation Group (E.K.M.), Brain and Mind Research Institute, University of Sydney, Camperdown, Australia. T2 axial MRI scans demonstrate demyelinating lesions during the first acute event and during convalescence. Patient A (C) had globular deep white matter Go to Neurology.org/nn for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of lesions on acute scan (left panel), which show residual gliosis on convalescent scan and no new lesions (right panel). Patient B (D) had inflammatory lesions in the article. The Article Processing Charge was paid by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which basal ganglia and white matter on acute scan (left panel), with complete resolution on convalescent scan and no new lesions (right panel). Ab 5 antibody; permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially. ADEM 5 acute disseminated encephalomyelitis; CEREB 5 cerebellar episode; Ig 5 immunoglobulin; MFI 5 mean fluorescence intensity; ON 5 optic neuritis; Neurology.org/nn © 2014 American Academy of Neurology 1 TM 5 transverse myelitis. ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

and normalization of MOG antibodies (figure 2 and purified IgG and immunoaffinity-purified MOG IgG appendix e-2). In both patients, upon treatment with from MOG antibody–positive sera, we immunolabeled MMF, MOG antibody decreased below the threshold HEK293MOG1 and HEK293Ctl cells on live cells by of positivity (figure 2, A and B). FACS (figure 3B) and on fixed MO3.13MOG1 cells Loss of cytoskeleton organization by MOG antibody or by immunocytochemistry (figure 3C) and showed purified IgG from children with demyelinating diseases. a positive immunostaining compared to MOG Human oligodendrocyte MO3.13MOG1 cells expressed antibody–negative sera, suggesting that protein G–purified IgG includes MOG-specific IgG. Due to

Page 34 MOG at their surface, whereas no MOG expression was observed on MO3.13Ctl cells (figure 3). MO3.13 cells small volumes of pediatric sera, we used protein also expressed oligodendrocyte markers, such as 29,39- G–purified IgG in pathogenic experiments. Next, we cyclic nucleotide 39-phosphodiesterase (CNPase), galac- treated fixed and live MO3.13MOG1/Ctl cells with IgG tocerebroside (GalC), oligodendrocyte marker O4, from MOG antibody–positive and –negative patients vimentin, and c-series ganglioside-specific antigen with DEM and healthy controls (HCs). Then, all cells (A2B5) (figure 3A). Myelin basic protein (MBP), a were immunolabeled for b-tubulin (marker of specific marker of mature oligodendrocytes, was microtubule) or F-actin (marker of thin filaments). We observed only in PMA-differentiated MO3.13MOG1 quantified results and expressed them by the F-actin and cells (figure 3A), suggesting that undifferentiated b-tubulin relative enrichments in the cytoplasm and MO3.13 cells are immature oligodendrocytes. Using perinuclear region over the entire cell. All results were

Neurology: Neuroimmunology & Neuroinflammation 5 ª 2014 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Student spotlight Ben Russell, Bachelor of Medical Science (Hons)

Ben Russell graduated in 2016 with a “Both Michael and Kim were amazing Bachelor of Medical Science (Hons), after supervisors,” says Ben. “Through Michael completing his final honours project we had the ability to go straight to the at Brain and Mind Centre. His project, hospital and change protocols to help titled: ‘Novel sources of tumour-derived collect samples. Kim had all the expertise biomarkers: neurosurgical CUSA aspirates and know-how when it came to processing as an enriched source of exosomal and analysing them. If either were just biomarkers’ won the University Medal for one step further removed, this project its high marks and outstanding quality. wouldn’t have been possible. I think this really validates a lot of what gets said about “My project involved analysing brain places like Brain and Mind Centre – the tumour material to potentially develop integration of clinical services and research new biomarkers to aid in diagnosis and is such an invaluable relationship.” Neuroimmunology monitoring of tumour behaviour,” says Ben. “I was able to identify specific molecules found in more lethal tumours, compared to less aggressive ones.”

Ben’s project was supervised by Dr Kim Kaufman, Head of NeuroOncology Biomarker Discovery and Translational Research, and Associate Professor Michael Buckland, Head of the Molecular Neuropathology Program at Brain and Mind Centre and Head of the Department of Neuropathology at Royal Prince Alfred Hospital.

Ben Russell, University Medal recipient.

Ben Russell Bachelor of Medical Science (Hons)

“I think this really validates a lot of what gets said about places like the Brain and Mind Centre - the integration of clinical services and research is such an invaluable relationship.” Page 35 ForeFront Ageing and Neurodegeneration _

At the forefront of research into ageing and neurodegeneration. The University of Sydney Page 36 ForeFront Ageing and Neurodegeneration Our core business

The ForeFront Ageing and Neurodegeneration team is committed to discovering early detection methods, identifying new treatments and understanding the underlying mechanisms of neurodegenerative disease.

Neurodegenerative diseases are becoming Our long-term research aims are to be able

increasingly prevalent in our ageing to improve and expedite diagnosis and to ForeFront Ageing and Neurodegeneration population. They have a devastating impact better understand how neurodegenerative on those affected and their families and processes work so that we can treat and place a huge economic and social impact potentially halt these debilitating diseases. on our society. Our research groups work together to help reduce this impact by Our collaborative research program improving the services offered to those incorporates several research groups affected, enhancing support for carers and and laboratories, all focused on different offering new hope through clinical trials but interrelated aspects of ageing and and the development of novel treatments. neurodegeneration.

Our research covers most neurodegenerative disorders, including frontotemporal dementia, motor neurone disease, Parkinson’s disease, dementia with Lewy bodies, and Alzheimer’s disease, as well as healthy brain ageing. Our core business Page 37 The Forefront team ForeFront Dementia and Movement ForeFront Neurodegeneration Research Disorders Laboratory, led by Laboratory, led by Associate Professor Professor Glenda Halliday Kay Double Our laboratory studies the origin and Our research is focused on understanding development of neurodegenerative the cause and neurodegenerative processes dementias and movement disorders. in Parkinson’s disease and other movement Our focus is on how neurodegeneration disorders so that we can better treat and manifests when symptoms first show and ultimately prevent these conditions. Our how this relates to genetic makeup, changes laboratory-based research focuses on identified in the brain, and blood markers of understanding how degenerative disorders, sydney.edu.au/brain-mind different pathologies. The aim is to identify such as Parkinson’s disease, dementia with and validate biomarkers that could be Lewy bodies and motor neurone disease, used in the diagnosis of neurodegenerative damages brain and nerve cells. We are also diseases and/or for monitoring responses researching how we can achieve a slower to new classes of drugs for these disease progression and better quality of debilitating disorders. life for patients. We work to develop better and earlier diagnostic tools and targeted ForeFront Neurogenetics and treatment strategies for Parkinson’s disease. Epigenetics Research Group, led by Associate Professor Jonathon Kwok ForeFront Clinical Parkinson’s Disease Our group studies the relationship between and Dementia with Lewy Bodies Research genetic changes and features of dementia Group, led by Professor Simon Lewis and related disorders. We also examine Our research is dedicated to improving the lifestyle and epigenetic factors in these quality of life for people with Parkinson’s diseases. Our research studies genetic disease, dementia with Lewy bodies and variants in specific genes that have been related disorders and ultimately, to finding implicated in sporadic and heritable forms a cure for these diseases. By working with of dementia and other neurodegenerative people affected by parkinsonism, we aim diseases. We focus on understanding how to find ways to predict the disease and

Brain and Mind Centre Annual Report 2015-16 genetic mutations cause or increase the to stem its progression. We work closely risk of disease to work towards better with other researchers who focus on brain treatment strategies. conditions related to Parkinson’s disease. We also collaborate with NeuroSleep, the ForeFront Genetics of Parkinson’s Centre for Translational Sleep and Circadian Disease Research Group, led by Neurobiology, which seeks to better Professor Carolyn Sue understand the relationship between sleep Our research aims to improve diagnostic and a healthy brain. methods and genetic testing for patients with Parkinson’s disease and other inherited forms of movement disorders. By identifying causative genes involved in these disorders, we are able to create patient-derived cell models with biologically relevant levels of abnormal proteins to further understand pathogenic mechanisms of disease. Our experiments have led to the discovery of novel disease pathways and new The University of Sydney treatment approaches. Page 38 ForeFront Motor Neurone Disease Research ForeFront Healthy Brain Ageing Program, Group, led by Professor Matthew Kiernan led by Professor Sharon Naismith We are a multidisciplinary team focused on We aim to determine whether changes clinical neurology. We work to understand in vascular risk factors, mood, sleep and the mechanisms behind neurodegenerative lifestyle can effectively reduce cognitive diseases, develop novel diagnostic tools decline, symptoms of depression and and trial new treatment strategies. We dementia-related brain changes in later are currently investigating mechanisms, life. Our research targets modifiable risk biomarkers and possible prevention factors by providing early identification, strategies for neurodegeneration in motor intervention and prevention programs neurone disease, frontotemporal dementia, for people at risk for dementia. We chemotherapy-induced neurotoxicity, evaluate clinical interventions including stroke, Machado-Joseph disease, spinal brain training programs, group-based muscular atrophy and other inherited psychoeducation programs to improve neuropathies. We also conduct clinical sleep disturbance, home-based exercise trials to investigate potential treatments programs for people with early-stage for motor neurone disease, chronic dementia, and the development of inflammatory demyelinating polyneuropathy internet-based tools to improve health and ForeFront Ageing and Neurodegeneration and other disorders. wellbeing, reduce depression and minimise vascular risk factors in older adults. Frontier Frontotemporal Dementia Research Group, led by Professor John Hodges and Associate Professor Olivier Piguet Frontotemporal dementia is the second most common degenerative disease that causes dementia in younger adults. Our research group is dedicated to identifying better ways to diagnose frontotemporal dementia, finding the cause and developing effective treatments for the condition. Our multidisciplinary research examines the neurological, psychological and biological brain function in frontotemporal dementia, as well as how the disease impacts on the lives of patients and their families. Our core business

Patient at the Healthy Brain Ageing Clinic with Professor Sharon Naismith (right). Page 39 ForeFront Ageing and Neurodegeneration Highlights

Welcoming a sydney.edu.au/brain-mind world-leading team In 2016 Professors Glenda Halliday, John Hodges and Associate Professor Olivier Piguet joined the Brain and Mind Centre, along with their significant team of researchers.

As long-term collaborators, joining forces with our pre-existing

translational research teams at Professor Glenda Halliday. the Brain and Mind Centre has provided significant opportunities for advancing research into these highly debilitating disorders.

We welcome their internationally-renowned program of research, focused

Brain and Mind Centre Annual Report 2015-16 on developing treatments for dementia and other neurodegenerative diseases.

Professor John Hodges. The University of Sydney

Associate Professor Olivier Piguet. Page 40 Funding for NHMRC Fellowship success frontotemporal dementia The ForeFront Ageing and −− Dr Cristian Leyton- In 2016, Professor Glenda Neurodegeneration team was Moscoso: disentangling Halliday led a successful $17 highly successful in the 2015 aphasic syndromes in million NHMRC Program Grant NHMRC-ARC Dementia Research Alzheimer’s disease. titled Frontotemporal Dementia Development Fellowships. Eleven −− Dr Sivaraman Purushothuman: and Motor Neurodegenerative outstanding researchers in our Lewy bodies in patients with Syndromes. Frontotemporal team were awarded fellowships. dementia – determining degeneration of the brain is a ForeFront Ageing and Neurodegeneration common and unique leading cause of morbidity due to These were: mechanisms in relation a pathologically heterogeneous, −− Dr Camillo Hoyos: sleep-wake to Alzheimer’s disease. rapidly-progressing group of disorders with behavioural, disturbances and cardio- −− Dr Surabhi Bhatia: role language and motor deficits. metabolic dysfunction in at-risk of apolipoprotein D in dementia: a novel pathway Alzheimer’s disease and With this program grant, in neurocognitive decline. frontotemporal dementia. Professor Halliday’s internationally −− Dr Shantel Duffy: neuroimaging −− Professor Simon Lewis: recognised team will continue insights into sleep-wake predicting dementia and to develop the necessary tools dysfunction in older adults at Parkinson’s disease in the clinic. and therapies to effectively risk of developing dementia. −− Dr Rachel Tan: dual and diagnose, manage and treat −− Dr Angela D’Rozario: multiple proteinopathies these disorders, with a particular sleep, plasticity and in neurodegenerative focus on understanding the neurodegeneration: targeting dementias – risk factors, unusual genetics underpinning sleep to improve cognition in prognostic indicators and them and fast-tracking any mild cognitive impairment (MCI). clinical ramifications. potential treatments. −− Dr Loren Mowszowski: cognitive interventions Dr Rebekah Ahmed received an for older adults at risk of NHMRC Early-Career Fellowship dementia and with early-stage in 2016, titled Characterisation

neurodegenerative disease. of Eating Behaviour and Highlights −− Dr Sharpley Hsieh: cognition Metabolic Phenotypes in motion: characterisation Across Neurodegenerative and evolution of cognitive Diseases; Insights for Survival dysfunction in motor and Progression. neurodegeneration and frontotemporal dementia. −− Dr Fiona Kumfor: identifying novel markers to differentiate frontotemporal dementia from Alzheimer’s disease. Page 41 Woolcock Community and NeuroSleep Clinic Awards and promotions industry appointments The Woolcock Neurosleep Clinic The following team members In 2016, Professor Matthew was established at Brain and received awards in recognition of Kiernan was elected President Mind Centre in 2016 to advance research excellence in 2016: of the Australian and New collaborative research in −− Professor Simon Lewis: in Zealand Association of translational sleep and circadian recognition of his cutting-edge Neurologists (ANZAN). neurobiology. NeuroSleep is research and excellence in focused on improving cognition, teaching, Simon was promoted Associate Professor Kay Double workplace safety and health to Professor of Cognitive was re-elected to the position sydney.edu.au/brain-mind outcomes in patients with sleep Neurology at Sydney Medical of Executive Secretary of the concerns including shift workers, School, University of Sydney. Australasian Neuroscience Society patients with sleep disorders, in 2016, the peak professional −− Professor Matthew Kiernan: neurodegenerative diseases, body for neuroscience research Matthew was awarded the and/or mental health problems. in Australia and New Zealand. M.J. Eadie Award for Career She was also elected Chair Achievement in Neuroscience. The establishment of the of the Parkinson’s New South Neurosleep Clinic was the −− Dr Rebekah Ahmed: Rebekah Wales Advisory Group, a group result of our collaborations with was awarded the James Lance of researchers and clinicians the Woolcock Institute and a Young Investigator Award from who provide expert advice on $2.5 million NHMRC Centre of the Australian and New Zealand Parkinson’s disease to Parkinson’s Research Excellence grant in Association of Neurology and New South Wales. 2014 for NeuroSleep: Centre the Susie Harris Travelling for Translational Sleep and Fellowship from the Motor Professor Carolyn Sue became Circadian Neurobiology. Neurone Disease Research the only Australian to join the Institute of Australia. Wellcome Trust Centres of −− Professor Carolyn Sue: Excellence Review Panel in the Carolyn was awarded the United Kingdom, a philanthropic Australian Mitochondrial body providing funding to 14,000 Disease Foundation Community scientists worldwide.

Brain and Mind Centre Annual Report 2015-16 Award, as head of ForeFront Genetics of Parkinson’s Education Disease Research Group. For the past two years, Professor −− Dr Brianada Koentjoro: Simon Lewis has delivered a Brianada was awarded the highly successful teaching course, Presidential Award by the titled Masterclass: Diseases of the International Movement Ageing Brain. The course provides Disorder Society in Berlin, training to geriatricians, general for his research on Parkinson’s practitioners, physicians, allied disease, as part of ForeFront health workers, nurses and other Genetics of Parkinson’s healthcare providers in Australia Disease Research Group. and overseas, on the practical −− Benjamin Trist: a PhD student clinical aspects of common from the Neurodegeneration diseases affecting the ageing Research Laboratory, Benjamin brain, including: was named as Parkinson’s New −− Alzheimer’s disease South Wales Young Researcher

The University of Sydney of the Year, for his work on a −− Lewy body dementia new protein abnormality in the −− Parkinson’s disease Parkinson’s disease brain. −− stroke. Page 42 ForeFront Ageing and Neurodegeneration

Research grants awarded Members of our team received the following research grants:

A selective prevention trial Modifying the trajectory of Brain oxidative stress and using novel pharmacotherapies insidious late life cognitive cognitive function in older in an older age cohort at risk decline using computerised adults with diabetes and for depression cognitive training pre-diabetes who are ‘at risk’ Led by: Naismith, S.L., Led by: Valenzuela, M. and of dementia Christensen, H. and Hickie, I.B. Naismith, S.L. Led by: Hoyos, C., Naismith, S.L., Granting body: NHMRC Granting body: NHMRC Colagiuri, S. and Duffy S. Project Grant Project Grant Granting body: Diabetes Australia Years: 2014–16* Years: 2015–18 Year: 2017 Amount: $947,670 (2014: $416,068; Amount: $715,764 (2015: $196,441, Amount: $59,902 2015: $411,068, 2016: $120,534) 2016: $186,441, 2017: $176,441, *extended to 2017 2018: $156,441) PRT MEDIC: Progressive Resistance Training for Metabolic NeuroSleep: the Centre ARTFUL: a program for people Syndrome and Depression for Translational Sleep and living with dementia Integrated Care: a randomised

Circadian Neurobiology Led by: Museum of Contemporary controlled trial Highlights Led by: Grunstein, R., Rajaratnam, Art (Filopevic, Y.), Naismith, S.L. Led by: Mavros, Y., Fiatarone S.W., Naismith, S.L., Eckert, D., and Alzheimer’s Australia. Singh, M., Naismith, S.L., Lewis, S.J.G., Glozier, N., Cistulli, Granting body: Vincent Fairfax Caterson, I. and Celermajer, D. P., Wong, K., Marshall, N. and Family Foundation Granting body: Diabetes Australia Robinson, P. Years: 2015–17 Year: 2017 Granting body: NHMRC Centre of Amount: $220,000 Amount: $59,837 Research Excellence Years: 2014–18 Amount: $2,496,739 Page 43 Investigating the utility of A therapeutic intervention in oxidative stress as a biomarker for Alzheimer’s disease intranasal cognitive decline and dementia: a oxytocin administration to longitudinal magnetic resonance enhance emotion processing and imaging study in ‘at risk’ older reduce caregiver burden adults and Alzheimer’s disease Led by: McCade, D., Naismith, S.L. Led by: Duffy, S. and Naismith, S.L. and Guastella, A. Granting body: Mason Foundation Granting body: Alzheimer’s National Medical Program Australia Dementia sydney.edu.au/brain-mind Year: 2016 Research Funds Amount: $59,672.55 Year: 2015 Amount: $50,000 HOMEeCare: caring for the dementia caregiver and their Does the use of intranasal loved one via the HOMeCare oxytocin improve emotional exercise and mindfulness for functioning and reduce carer health program burden in Alzheimer’s disease? Led by: Fiatarone Singh, Led by: Naismith, S.L., McCade, D. M.A., Naismith, S.L., Simic, M. and Guastella, A. and Mavros Y. Granting body: ANZ Trustees Granting body: Dementia Mason Foundation Collaborative Research Centres Year: 2015 Year: 2016 Amount: $59,300 Amount: $99,856.09 Utilising novel biomarkers Assessing sleep-wake cycles in to develop predictors of paediatric traumatic brain injury neurodegeneration using actigraphy Led by: Halliday, G.M., Grunstein, Led by: Lah, S. and Naismith, S.L. R.R., Naismith, S.L., Hodges, Brain and Mind Centre Annual Report 2015-16 Granting body: School J.R., Piguet, O., D’Rozario, A. of Psychology Research and Wang, Z. Infrastructure Block Grant, Granting body: Sydney Research University of Sydney Excellence Initiative (SREI) Year: 2016 Year: 2017-2019 Amount: $10,845 Amount: $150,000

Evaluation of a 12-week combined A randomised controlled trial psychoeducation and home- of an enriched environment based exercise program on mood intervention to improve sleep and and wellbeing in older adults with cognitive outcomes in older adults early Alzheimer’s disease at risk from dementia Led by: Duffy, S., Naismith, S.L., Led by: Anderson, C., Naismith, Jeon, Y-H. and Clemson L. S.L., Rajaratnam, S.W. and Granting body: Alzheimer’s Cain, S.W. Australia Dementia Granting body: Research Funds The Mason Foundation

The University of Sydney Year: 2015 Years: 2015 Amount: $50,000 Amount: $35,000 Page 44 ForeFront Ageing and Neurodegeneration 2017 and beyond

We are committed to the early detection of and developing treatments for neurodegenerative diseases to understand their underlying disease mechanisms. Our goal for 2017 is to work cohesively in our new home at Brain and Mind Centre, in order to establish new clinics for people with neurodegenerative diseases, ForeFront Ageing and Neurodegeneration conduct new trials of potential therapies, discover new ways of measuring the success of these trials and to continue work on determining disease mechanisms to target in future treatments.

Professor Simon Lewis working with his patient. 2017 and beyond Page 45 ForeFront Ageing and Neurodegeneration Key projects and clinical trials

Key research projects Clinical trials Nodal function in peripheral Defining Lewy Body dementia A randomised, cross-over neuroinflammatory This research resulted in the study to evaluate efficacy and sydney.edu.au/brain-mind disorders target antigens, publication of new diagnostic tolerability of FLX-787 in patients functional significance and criteria for the diagnosis and with motor neurone disease treatment response. management of dementia with This clinical trial is investigating Collaborators: Professor Matthew Lewy bodies, published in highly spasticity and cramps in patients Kiernan, Dr Nidhi Garg, Dr cited journal Neurology. It was with motor neurone disease. Susanna Park, Professor John also the fourth consensus report Pollard, Dr Emily Mathey and of the Dementia with Lewy Body Collaborators: Professor Matthew Professor Steve Vucic Diagnosis consortium. Kiernan, Dr Susan Mathers, Dr Funding body: National Robert Henderson, Neuroscience Health and Medical Research Collaborators: Dementia with Trials Australia and Thomas Council (NHMRC) Lewy Body Diagnosis Consortium Wessel, Flex-Pharma (including Professor Glenda Halliday) Funding body: Flex-pharma Project MinE Collaborators: Professor Leonard Validation of the Movement van den Berg and Professor Disorders Society Parkinson’s Matthew Kiernan disease diagnostic criteria Funding bodies: Motor Neurone Brain and Mind Centre was Disease Research Institute of the only site in the southern Australia, ALS Centrum Nederland hemisphere to take part in and ALS Nederland the validation of the newly Brain and Mind Centre Annual Report 2015-16 proposed diagnostic criteria for The Lighthouse Project Parkinson’s disease. Collaborators: Professor Matthew Kiernan, Professor Collaborators: Ron Postuma Julian Gold, Professor Dominic (Montreal) and Daniela Berg (Kiel) Rowe, Professor Steve Funding body: Michael J Fox Vucic, Dr Susan Mathers and Foundation and the International Professor Paul Talman Movement Disorders Society Funding body: Cure for MND Foundation and Australian MND Association Research Institute of Australia (MNDRIA)

A new pathology in the Parkinson’s disease brain Collaborators: Brain and Mind Centre, University of Bordeaux

The University of Sydney (France), King’s College London (United Kingdom), Neuroscience Research Australia (Sydney) and University of Technology Sydney (UTS) Funding body: Parkinson’s NSW Page 46 ForeFront Ageing and Neurodegeneration Key publications

The ForeFront Motor Neurone Disease Research Group 1. Menon, P., Geevasinga, N., 5. Van Rheenen, W., Shatunov, Yiannikas, C., Howells, J., A., Dekker, A.M., et al. Kiernan, M.C. and Vucic, PARALS Registry; SLALOM S. (2015). Sensitivity and Group; SLAP Registry; FALS specificity of threshold Sequencing Consortium; tracking transcranial magnetic SLAGEN Consortium; NNIPPS stimulation for diagnosis of Study Group, Blair, I., Zhang, amyotrophic lateral sclerosis: K., McCann, E.P., Fifita, J.A., a prospective study. Lancet Nicholson, G.A., Rowe, D.B., Neurology, May; 14(5):478-84. Pamphlett, R., Kiernan, M.C.,

Grosskreutz, J., Witte, O.W., ForeFront Ageing and Neurodegeneration 2. Farrar, M.A., Park, S.B., Vucic, Ringer, T., Prell, T., Stubendorff, S., Carey, K.A., Turner, B.J., B., Kurth, I., Hübner, C.A., Gillingwater, T.H., Swoboda, Leigh, P.N., Casale, F., Chio, A., K.J. and Kiernan, M.C. (2016). Beghi, E., Pupillo, E., Tortelli, Emerging therapies and R., Logroscino, G., Powell, J., challenges in spinal muscular Ludolph, A.C., Weishaupt, J.H., Associate Professor Kay Double. atrophy. Annals of Neurology, Robberecht, W., Van Damme, Dec 27. doi: 10.1002/ana.24864. P., Franke, L., Pers, T.H., Brown, R.H., Glass, J.D., Landers, J.E., 3. Garg, N., Park, S.B., Vucic, Hardiman, O., Andersen, P.M., S., Yiannikas, C., Spies, Corcia, P., Vourch, P., Silani, J., Howells, J., Huynh, W., V., Wray, N.R., Visscher, P.M., Matamala, J.M., Krishnan, A.V., de Bakker, P.I., van Es, M.A., Pollard, J.D., Cornblath, D.R., 7. Shibuya, K., Park, S.B., Pasterkamp, R.J., Lewis, C.M., Reilly, M.M. and Kiernan, M.C. Geevasinga, N., Menon, P., Breen, G., Al-Chalabi, A., van (2016). Differentiating lower Howells, J., Simon, N.G., Huynh, den Berg, L.H, and Veldink, motor neurone syndromes. W., Noto, Y., Götz, J., Kril, J.J., J.H. (2016). Genome-wide Journal of Neurology, Ittner, L.M., Hodges, J., Halliday, association analyses identify Neurosurgery, and Psychiatry, G., Vucic, S. and Kiernan, M.C. new risk variants and the genetic Dec 21. pii: jnnp-2016-313526. (2016). Motor cortical function architecture of amyotrophic doi: 10.1136/jnnp-2016-313526. determines prognosis in sporadic lateral sclerosis. Nat Genet, doi: ALS. Neurology, 2; 87(5):513-20.

4. Ahmed, R.M., Irish, M., Piguet, 10.1038/ng.3622. Key publications O., Halliday, G.M., Ittner, 8. Hogden, A., Greenfield, D., 6. Park, S.B., Vucic, S., Cheah, L.M., Farooqi, S., Hodges, Nugus, P. and Kiernan, M.C. B.C., Lin, C.S., Kirby, A., J.R. and Kiernan, M.C. (2016). (2015). Development of a model Mann, K.P., Zoing, M.C., Amyotrophic lateral sclerosis to guide decision making in Winhammar, J. and Kiernan, and frontotemporal dementia: multidisciplinary care. Health M.C. (2016). Flecainide in distinct and overlapping Expectations, 18:1769-82. Amyotrophic Lateral Sclerosis changes in eating behaviour as a Neuroprotective Strategy and metabolism. Lancet (FANS): a randomized Neurology, Vol 15, pp 332-342. placebo-controlled trial. EBioMedicine, 2015; 2(12):1916-22. Page 47 The Neurodegeneration The Clinical Parkinson’s Disease and Dementia with Research Laboratory Lewy Bodies Research Group 1. Davies, K., Hare, D., Bohic, S., 1. Muller, A.J., O’Callaghan, C., 4. Gilat, M., Shine, J.M., Walton, James, S., Billings, J., Finkelstein, Walton, C.C., Shine, J.M. and C.C., O’Callaghan, C., Hall, D., Doble, P. and Double, K.L. Lewis, S.J.G. Retrospective J. and Lewis, S.J.G. Brain (2015). A comparative study neuropsychological profile activation underlying turning of metal quantification in of Parkinson’s disease in Parkinson’s disease patients neurological tissue using laser patients prior to developing with and without Freezing ablation-inductively coupled visual hallucinations. J of Gait: a virtual reality fMRI plasma-mass spectrometry Ger Psych Neur, (accepted study. npj Parkinson’s Disease, imaging and x-ray fluorescence October 2016). (accepted August 2015). sydney.edu.au/brain-mind microscopy. Analytical Chemistry, 87, 6639-45. 2. O’Callaghan, C., Hornberger, 5. Szeto, J.Y., O’Callaghan, C., M., Balsters, J.H., Halliday, Shine, J.M., Mowszowski, L., 2. Davies, K.M., Julian F.B., G.M., Lewis, S.J.G. and Walton, C.C., Naismith, S.L., Mercer, J.F.B., Chen, N. and Shine, J.M. (2016). Cerebellar Halliday, G.M. and Lewis, Double, K.L. (2016). Copper atrophy in Parkinson’s disease S.J.G. The relationships dyshomeostasis in Parkinson’s and its implication for between mild cognitive disease: implications for network connectivity. Brain, impairment and phenotype pathogenesis and indications 139:845-55. in Parkinson’s disease. npj for novel therapeutics. Parkinson’s Disease, (accepted Clinical Science, 130, 565-574. 3. Trenkwalder, C., Chaudhuri, July 2015). K.R., García Ruiz, P.J., LeWitt, 3. Hare, D.J. and Double, K.L. P., Katzenschlager, R., Sixel- 6. Shine, J.M., Muller, A.M., (2016). Iron and dopamine: a Döring, F., Henriksen, T., Hornberger, M., O’Callaghan, toxic couple. Brain, Apr; 139(Pt Sesar, Á., Poewe, W., Baker, C., Halliday, G.M. and Lewis, 4):1026-35. M., Ceballos-Baumann, A., S.J.G. (2015). Abnormal Deuschl, G., Drapier, S., connectivity between Ebersbach, G., Evans, A., the default mode and the Fernandez, H., Isaacson, S., visual system underlies van Laar, T., Lees, A., Lewis, the manifestation of visual

Brain and Mind Centre Annual Report 2015-16 S.J.G., Martínez Castrillo, J.C., hallucinations in Parkinson’s Martinez-Martin, P., Odin, disease: a task-based fMRI P., O’Sullivan, J., Tagaris, G. study. npj Parkinson’s Disease, and Wenzel, K. (2015). Expert doi 10.1038/npjparkd.2015.3. Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease – clinical practice recommendations. Parkinsonism Relat Disord, 21:1023-30. The University of Sydney Page 48 The Genetics of Parkinson’s The Healthy Brain Ageing Program Disease Research Group 1. McKinnon, A., Lagopoulos, 4. Duffy, S.L., Lagopoulos, J., 1. Davis, R.L., Liang, C. J., Terpening, Z., Grunstein, Terpening, Z., Hickie, I.B. and Sue, C.M. (2016). A R., Hickie, I., Batchelor, J., and Naismith, S.L. (2016). comparison of current serum Lewis, S., Duffy, S., Shine, J. Association of anterior biomarkers as diagnostic and Naismith, S. (2016). Sleep cingulate glutathione with indicators of mitochondrial disturbance in mild cognitive sleep apnea in older adults diseases. Neurology, May 24; impairment is associated ‘at-risk’ for dementia. Sleep, 86(21):2010-5. with alterations in the brain’s 39(4): 899-906. default mode network. 2. Mazzulli, J.R., Zunke, F., 5. Jayaweera, H., Hickie, I., Duffy, Behavioral Neuroscience, Tsunemi, T., Toker, N.J., Jeon, S., Hermens, D., Mowszowski, 130(3), 305-315. S., Burbulla, L.F., Patnaik, L., Diamond, K., Terpening, S., Sidransky, E., Marugan, 2. Mowszowski, L., Lampit, A., Z., Paradise, M., Lewis, S., J.J., Sue, C.M. and Krainc, Walton, C. and Naismith, Lagopoulos, J. and Naismith, D. (2016). Activation of S. (2016). Strategy-based S. (2015). Mild cognitive β-glucocerebrosidase reduces cognitive training for impairment subtypes in pathological α-synuclein and improving executive functions older people with depressive restores lysosomal function in in older adults: a systematic symptoms: relationship Parkinson’s patient midbrain ForeFront Ageing and Neurodegeneration review. Neuropsychology with clinical variables and neurons. J Neurosci, Jul 20; Review, 26(3), 252-270. hippocampal change. Journal 36(29):7693-706. of Geriatric Psychiatry and 3. Terpening, Z., Lewis, S., Neurology, 28(3), 174-183. Yee, B., Grunstein, R., Hickie, I. and Naismith, S. 6. Diamond, K., Mowszowski, (2015). Association between L., Cockayne, N., Norrie, sleep-disordered breathing L., Paradise, M., Hermens, and neuropsychological D., Lewis, S., Hickie, I. performance in older and Naismith, S. (2015). adults with mild cognitive Randomized controlled trial impairment. Journal of of a healthy brain ageing Alzheimer’s Disease, 46(1), cognitive training program: 157-165. effects on memory, mood, and sleep. Journal of Alzheimer’s Disease, 44, 1181-1191. Key projects and clinical trials Page 49 The Lambert Initiative for Cannabinoid Therapeutics _

Alleviating human suffering with medicinal cannabis. The University of Sydney Page 50 The Lambert Initiative for Cannabinoid Therapeutics Our core business

The Lambert Initiative for Cannabinoid Therapeutics was founded in 2015, thanks to an unprecedented pledge of $33.7 million to the University by Barry and Joy Lambert – the largest single gift in the history of the University of Sydney. The Lambert Initiative, based at Brain and Mind Centre, is a long-term research program exploring the medicinal potential of the cannabis plant. The Lambert Initiative for Cannabinoid Therapeutics

Advocacy and education

Our vision is to conduct the high quality In parallel with our scientific endeavours, research required to discover, develop and the Lambert Initiative also acts in an optimise safe and effective cannabinoid advocacy and educational capacity, therapeutics in Australia and beyond. providing synthesis of evidence and guidance for clinicians, targeting The Lambert Initiative provides national consumers, health professionals and and international leadership in the politicians and influencing regulatory science of medicinal cannabinoids and approaches and public health policy. in the discovery and development of cannabis-based medicines. Our activities For many patients and families, the future span a wide spectrum of basic science of medicinal cannabis is one of hope: and clinical activities, from plant science, hope that legislation will change to make cellular and preclinical pharmacology, to medical cannabis and future cannabinoid medicinal chemistry and drug discovery, drugs more accessible. Hope that attitudes change to encourage practitioners to with the ultimate goal of producing Our core business cannabinoid-based medicines and prescribe medicinal cannabis. A key aspect ensuring their availability to patients. of the Lambert Initiative’s vision is to provide tangible scientific evidence to help translate hope into reality. Page 51 The Lambert Initiative for Cannabinoid Therapeutics Highlights sydney.edu.au/brain-mind

Survey into cannabis use for epilepsy management Published in Epilepsy & Behaviour, the Epilepsy Action Australia study, in partnership with the Lambert Initiative, surveyed 976 respondents to examine cannabis use in people with epilepsy, their Dr Michael Bowen (right) with University of Sydney Dean of Science, Professor Trevor Hambley. reasons for using cannabis and any perceived benefits self-reported by consumers (or their carers).

The survey revealed that The PELICAN study 14 percent of people with epilepsy have used cannabis products as In our first year of operation, we The PELICAN study, launched a way to manage seizures. The established a state-of-the-art in July 2015, gives a voice to study also showed that of those Brain and Mind Centre Annual Report 2015-16 research facility at Brain and families living with epilepsy, with a history of cannabis product Mind Centre and have recruited to share their experiences of use, 90 percent of adults and quality national and international wanting to use cannabis to treat 71 percent of parents of children researchers to the team. seizures. The study involves with epilepsy reported success interviews with parents and the in managing seizures after using In addition, we have: collection and chemical analysis cannabis products. −− established multidisciplinary of oils and extracts already being used in the community, to link collaboration to support Across all respondents, the the cannabinoid content to its our research main reasons for trying cannabis therapeutic effects. Parents −− established a supply of purified products were to manage have the option of finding out the cannabinoids from industrial treatment-resistant epilepsy and results of the analysis and are hemp and organic syntheses to reduce side effects compared provided with education on the to standard antiepileptic drugs. −− discovered novel therapeutic cannabis plant, its constituents, The number of past antiepileptic indications for some and current clinical safety data. cannabinoids and novel drugs used was a significant predictor of medicinal cannabis modes of action The PELICAN study has the use in both adults and children −− made important translational potential to provide better The University of Sydney with epilepsy. discoveries that deepen our understanding of the cannabinoid understanding of the efficacy components that provide these of cannabinoid therapeutics therapeutic effects, which may −− used scientific expertise lead to novel medications that and evidence to influence could prove extremely effective. the regulatory landscape. Page 52 Cannabinoid replacement Medical cannabis trial for drug trial to help chemotherapy patients cannabis smokers quit Awards A clinical trial using a new form This pioneering study builds on Dr Michael Bowen from Brain and of cannabis developed by our our team’s previous work, which Mind Centre’s Lambert Initiative, researchers is assessing the demonstrated that Sativex® was awarded the Eureka Prize use of the drug to prevent suppressed cannabis withdrawal for Outstanding Early-Career nausea and vomiting in people symptoms in an inpatient setting. Researcher on 1 September 2016. undergoing chemotherapy. The prestigious Eureka Prize If the trial of Sativex® proves rewards excellence in the fields of The trial is part of the NSW effective, it could be a promising scientific research and innovation, Government’s $21 million breakthrough in the treatment science leadership, school commitment to support medicinal of cannabis dependence, science, and science journalism cannabis reforms. It will be which affects one in ten users. and communication. coordinated at the NHMRC Clinical Cannabis dependence can Trials Centre and aims to develop contribute to an array of health Dr Bowen's award recognised a better understanding of how problems, including cognitive, his work on discovering and cannabis products can provide psychiatric, cardiovascular and developing novel treatments The Lambert Initiative for Cannabinoid Therapeutics relief to patients undergoing respiratory disorders. for serious brain disorders. He chemotherapy who have not had has established that oxytocin their symptoms controlled by Existing treatments for cannabis and novel molecules that target standard treatments. dependence have had only the brain’s oxytocin system modest success. Current best are effective treatments for This trial represents a major practice counselling approaches, alcohol-use disorders, advance for cannabis-based such as cognitive behavioural substance-use disorders medications. It’s an oral capsule therapy (CBT), have a 70 to 80 and social disorders. of reliable doses of cannabinoids percent relapse rate within six extracted from cannabis months. Treatments for acute Dr Bowen has demonstrated that plants, under pharmaceutical cannabis withdrawal have similar exogenously administered oxytocin grade conditions. relapse rates. is able to powerfully inhibit alcohol consumption. He has As with treatment of many other also shown that oxytocin blocks addictions, our team is keen to alcohol’s ability to act as key examine the effects of combining addiction pathways in the brain. counselling with medication, an He is currently involved in a phase approach proven to be more II clinical trial to translate these effective than using either effects on humans. approach in isolation. Dr Bowen is also one of the lead inventors of a series of small molecules that powerfully Highlights stimulate the brain oxytocin system, overcoming some of the limitations of administering oxytocin. Clinical trials to test one of these molecules in humans is underway.

Barry Lambert announces the donation

to form the Lambert Initiative. Page 53 The Lambert Initiative for Cannabinoid Therapeutics 2017 and beyond

Cannabinoid researchers join forces sydney.edu.au/brain-mind In May 2017, the University of Sydney and The two Lambert research centres will Thomas Jefferson University (TJU) in explore collaborations in: Philadelphia, USA agreed to collaborate on −− clinical trials of extracts of cannabis education and research on the therapeutic plants as adjuncts or alternatives to uses of cannabinoids. Both universities conventional prescription medications have dedicated centres, supported by the in treating and preventing disease generous funding of the Lambert family, to −− academic exchange to facilitate the conduct their work on medicinal cannabis. training of scientists and clinicians in the cannabinoid scientific space This is an exciting opportunity for research collaboration to identify novel cannabis- −− educational programs for derived treatments for epilepsy, pain and physicians, other medical metabolic disorders. professionals and the public.

The recent launch of the Lambert Center for the Study of Medicinal Cannabis and Hemp within the Institute for Emerging Health Professions adds to TJU’s healthcare and medical research focus. Brain and Mind Centre Annual Report 2015-16 The University of Sydney

The Lambert Iniative research team left to right: Associate Professors Jonathon Arnold and David Allsop, Professor Iain McGregor, Dr Michael Bowen. Page 54 The Lambert Initiative for Cannabinoid Therapeutics Key publications

1. Suraev, A.S., Todd, L., 4. Banister, S.D., Longworth, 7. Luckett, T., Phillips, J., Bowen, M.T., Allsop, D.J., M., Kevin, R., Sachdev, Lintzeris, N., Allsop, D., Lee, McGregor, I.S., Ireland, C. S., Santiago, M., Stuart, J., Solowij, Martin, J., Lam, and Lintzeris, N. (2017). J. and Kassiou, M. (2016). L., Aggarwal, R., McCaffery, An Australian nationwide Pharmacology of Valinate N., Currow, D., Chye, R., survey on medicinal and tert-Leucinate Lovell, M., McGregor, I. and cannabis use for epilepsy: synthetic cannabinoids Agar, M. (2016). Clinical trials history of antiepileptic drug 5F-AMBICA, 5F-AMB, of medicinal cannabis for treatment predicts medicinal 5F-ADB, AMB-FUBINACA, appetite-related symptoms cannabis use. Epilepsy Behav, MDMB-FUBINACA, MDMB- from advanced cancer: The Lambert Initiative for Cannabinoid Therapeutics doi:10.1016/j.ebeh.2017.02.005. CHMICA, and their analogues. a survey of preferences, ACS Chem Neurosci, 7(9), attitudes and beliefs among 2. Arnold, J.C., Allsop, D., 1241-1254. doi: 10.1021/ patients will to consider Lintzeris, N. and McGregor, acschemneuro.6b00137. participation. Intern Med J, I.S. (2016). Pharmacological 46: p.1269-1275. actions and associated 5. Banister, S.D., Moir, M., Stuart, therapeutic levels of J., Kevin, R.C., Wood, K.E., 8. Allsop, D., Kevin, R. and phytocannabinoids: an Longworth, M., McGregor, Arnold, J.C. (2016). Cannabis: evidence check review I.S. and Kassiou, M. (2015). pharmacokinetics and brokered by the Sax Institute Pharmacology of Indole pharmacodynamics in relation (www.saxinstitute.org.au) for and Indazole synthetic to patterns of use in handbook the NSW Ministry of Health. cannabinoid designer of drug and alcohol studies. K. Sax Institute, Sydney, Australia. drugs AB-FUBINACA, ADB- Wolff, J. White, and S. Karch, FUBINACA, AB-PINACA, (Eds). SAGE: London, UK. 3. Kevin, R.C., Wood, K.E., Stuart, ADB-PINACA, 5F-AB- J., Mitchell, A.J., Moir, M., PINACA, 5F-ADB-PINACA, 9. Allsop, D.J. and Hall, W.D. Banister, S.D. and McGregor, ADBICA, and 5F-ADBICA. (2016). International aspects I.S. (2017). Acute and residual ACS Chem Neurosci, 6(9), of cannabis use and misuse: effects in adolescent rats 1546-1559. doi: 10.1021/ the Australian perspective. resulting from exposure to the acschemneuro.5b00112. In. The Handbook of Cannabis novel synthetic cannabinoids and related Pathologies: AB-PINACA and AB-FUBINACA. 6. Banister, S.D., Stuart, J., Kevin, Biology, Diagnosis, Treatment Key publications J Psychopharmacol, R.C., Edington, A., Longworth, and Pharmacology, Edited by 269881116684336. doi: M., Wilkinson, S.M., McGregor, Victor R. Preedy. Elsevier. 10.1177/0269881116684336. I.S. and Kassiou, M. (2015). Effects of bioisosteric fluorine 10. Bennett, M.R., Arnold, J., in synthetic cannabinoid Hatton, S.N. and Lagopoulos, designer drugs JWH-018, J. (2017). Regulation of fear AM-2201, UR-144, XLR-11, extinction by long-term PB-22, 5F-PB-22, APICA, and depression: the roles of STS-135. ACS Chem Neurosci, endocannabinoids and 6(8), 1445-1458. doi: 10.1021/ brain derived neurotrophic acschemneuro.5b00107. factor. Behav Brain Res, 319: p.148-164. Page 55 11. Soethoudt, M., Grether, 13. Todd, S.M. and Arnold, J.C. 15. Clarke, D.J., Stuart, J., U., Fingerle, J., Grim, T.W., (2016). Neural correlates McGregor, I.S. and Arnold, Fezza, F., de Petrocellis, L., of interactions between J.C. (2016). Endocannabinoid Ullmer, C., Rothenhäusler, cannabidiol and Delta(9)- dysregulation in cognitive B., Perret, C., van Gils, N., tetrahydrocannabinol in mice: and stress-related brain Finlay, D., MacDonald, C., implications for medical regions in the Nrg1 mouse Chicca, A., Gens, M.D., Stuart, cannabis. Br J Pharmacol, model of schizophrenia. J., de Vries, H., Mastrangelo, 173(1): p. 53-65. Prog Neuropsychopharmacol N., Xia, L., Alachouzos, G., Biol Psychiatry, 2017, Jan Baggelaar, M.P., Martella, A., 14. Silveira, M.M., Arnold, J.C., 4; 72:9-15. doi: 10.1016/j. Mock, E.D., Deng, H., Heitman, Laviolette, S.R., Hillard, pnpbp.2016.08.006. Epub C.J., Celorrio, M., Aymerich,

sydney.edu.au/brain-mind L.H., Connor, M., Di Marzo, V., 2016 Aug 10. Gertsch, J., Lichtman, A.H., M.S. and Adams, W.K. Maccarrone, M., Pacher, P., (2016). Seeing through the 16. Brzozowska, N., Li, K.M., Glass, M. and van der Stelt, smoke: human and animal Wang, X.S., Booth, J., M. (2017). Cannabinoid CB2 studies of cannabis use and Stuart, J., McGregor, I.S. receptor ligand profiling endocannabinoid signalling and Arnold, J.C. (2016). ABC reveals biased signalling in corticolimbic networks. transporters P-gp and Bcrp and off-target activity. Nat. Neurosci Biobehav Rev, 76 (Pt do not limit the brain uptake Commun, 13958 doi: 10.1038/ B), 380-395. 2016 Sep 14. of the novel antipsychotic ncomms13958. and anticonvulsant drug cannabidiol in mice. PeerJ, 4: 12. Todd, S.M., Zhou, C., Clarke, p. e2081. D.J., Chohan, T.W., Bahceci, D. and Arnold, J.C. (2016). Interactions between cannabidiol and Delta9- THC following acute and repeated dosing: rebound hyperactivity, sensorimotor gating and epigenetic and

Brain and Mind Centre Annual Report 2015-16 neuroadaptive changes in the mesolimbic pathway. Eur Neuropsychopharmacol, pii: S0924-977X (16)32012- 0. doi: 10.1016/j. euroneuro.2016.12.004.

ACS Chemical Neuroscience Research Article Research Article

pubs.acs.org/chemneuro

Eﬀects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135 Samuel D. Banister,†,‡ Jordyn Stuart,§ Richard C. Kevin,∥ Amelia Edington,§ Mitchell Longworth,‡ Shane M. Wilkinson,‡ Corinne Beinat,†,‡ Alexandra S. Buchanan,⊥,# David E. Hibbs,∇ Michelle Glass,¶ Mark Connor,§ Iain S. McGregor,∥ and Michael Kassiou*,‡,◆ †Department of Radiology, Stanford University School of Medicine, Stanford, California 94305, United States ‡School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia §Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia ∥School of Psychology, The University of Sydney, Sydney, New South Wales 2006, Australia ⊥Center for Immersive and Simulation-based Learning, Stanford University School of Medicine, Stanford, California 94305, United States #Department of Anaesthesia, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia ∇Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia ¶School of Medical Sciences, The University of Auckland, Auckland 1142, New Zealand ◆Discipline of Medical Radiation Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia *S Supporting Information

ABSTRACT: Synthetic cannabinoid (SC) designer drugs featuring bioisosteric fluorine substitution are identified by forensic chemists and toxicologists with increasing frequency. Although terminal fluorination of N-pentyl indole SCs is sometimes known to improve cannabinoid type 1 (CB1) receptor binding affinity, little is known of the effects of fl uorination on functional activity of SCs. This study explores Figure 1. Selected natural and synthetic cannabinoids. the in vitro functional activities of SC designer drugs JWH-018, UR-144, PB-22, and APICA, and their respective terminally ffi CB1 and CB2 receptors, with psychoactivity attributed to nanomolar a nity SCs (CB1 Ki = 1.0 nM; CB2 Ki = 2.6 nM) The University of Sydney fl uorinated analogues AM-2201, XLR-11, 5F-PB-22, and STS- activation of the former.3 Generally, SCs are found as reported by Makriyannis and colleagues in 2001,7 and was 135 at human CB1 and CB2 receptors using a FLIPR adulterants in smoking mixtures of otherwise nonpsychoactive identified in consumer products by forensic researchers in membrane potential assay. All compounds demonstrated herbal blends and are intended to substitute for the intoxicating several countries in 2011.8,9 Anecdotal reports that AM-2201 agonist activity at CB1 (EC50 = 2.8−1959 nM) and CB2 ff 9 fl e ects of Δ -THC. Although these products are disingenuously possesses psychoactivity at submilligram doses in humans likely (EC50 = 6.5−206 nM) receptors, with the uorinated analogues generally showing increased CB1 receptor potency (∼2−5 marketed as incense and labeled “not for human consumption”, instigated the trend of bioisosteric fluorine substitution in other times). Additionally, the cannabimimetic activities and relative potencies of JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F- consumers are aware of the psychoactivity of such products and structurally related SC designer drugs. For example, South PB-22, APICA, and STS-135 in vivo were evaluated in rats using biotelemetry. All SCs dose-dependently induced hypothermia use them as technically legal cannabis substitutes. One of the Korea’s National Forensic Service reported no fluorinated SCs and reduced heart rate at doses of 0.3−10 mg/kg. There was no consistent trend for increased potency of fluorinated SCs over 10 earliest SC products, branded “Spice”, was analyzed in 2008 in 2010, but 90% of all seized SCs were fluorinated by 2013. the corresponding des-fluoro SCs in vivo. Based on magnitude and duration of hypothermia, the SCs were ranked for potency and found to contain the C8-homologue of CP 47,497 (CP Several dozen terminally fluorinated SCs have been reported by (PB-22 > 5F-PB-22 = JWH-018 > AM-2201 > APICA = STS-135 = XLR-11 > UR-144). 47,497-C8, 2) and an (aminoalkyl)indole analogue of WIN forensic laboratories worldwide, and the rate of emergence KEYWORDS: Cannabinoid, THC, JWH-018, AM-2201, XLR-11, PB-22 55,212-2 (3)4 known as JWH-018 (4), thereby accounting for appears to be increasing.6 ff 5 the anecdotal cannabimimetic e ects of this product. After the The SC sold as UR-144 (7, CB1 Ki = 150 nM; CB2 Ki = 1.8 active ingredients of Spice were identified, many governments nM) was first reported by Abbott Laboratories in 2010 during ynthetic cannabinoids (SCs) are the most rapidly growing were over 21 000 seizures of SCs, a more than 200-fold increase prohibited CP 47,497-C8 and JWH-018, forcing manufacturers their exploration of CB -selective ligands11,12 and has since 1 fi 2 S class of recreational “designer drugs”. The European since 2008. Many SCs have no precedent in the scienti c of Spice to circumvent restriction by substituting the active been identified in numerous forensic samples.9,13−15 The 5- Monitoring Centre for Drugs and Drug Addiction (EMCDDA) literature yet bear hallmarks of rational design. fluoro analogue of UR-144, sold as XLR-11 (8), has also been 9 9 constituents with other unregulated SCs. The iterative cycle of reports that, as of March 2015, 134 new SCs have been Like Δ -tetrahydrocannabinol (Δ -THC, 1; Figure 1), the SC identification, prohibition, and substitution has produced identified in consumer products, despite no prior reports of its identified in the European Union (EU) since 2008, with 30 principal bioactive component of cannabis, SCs typically exert hundreds of differently branded products, with names like structure in the scientific literature.16−19 In Korea, XLR-11 first 1 novel SCs formally notified in 2014 alone. In the United States agonist activity at both cannabinoid receptor subtypes, namely, “Kronic”, and “K2”, containing one or more SCs. appeared in 2012 and was the most frequently encountered SC (US) in 2010, the Drug Enforcement Administration’s National A popular design trend in the SC market currently is the by 2013.10 XLR-11 use is associated with adverse health effects, Forensic Laboratory Information System (NFLIS) reported 19 Received: April 2, 2015 incorporation of a terminal fluorine atom in variously including acute kidney injury (AKI)20,21 and cerebral distinct SCs across 3286 samples, but by 2012, there were 61 Accepted: April 28, 2015 substituted N-pentylindoles.6 The terminally fluorinated ischemia.22 Wiley and colleagues recently showed that XLR- fi 2 ffi SC variants identi ed in 41 458 cases. In the EU in 2013, there Published: April 28, 2015 analogue of JWH-018, AM-2201 (5), was one of several 11 (CB1 Ki = 24 nM; CB2 Ki = 2.1 nM) has binding a nities

© 2015 American Chemical Society 1445 DOI: 10.1021/acschemneuro.5b00107 1446 DOI: 10.1021/acschemneuro.5b00107 ACS Chem. Neurosci. 2015, 6, 1445−1458 ACS Chem. Neurosci. 2015, 6, 1445−1458 Page 56 Technical Facilities _

State of the art research and clinical facilities. Technical Facilities Page 57 Technical Facilities Our core business

Brain and Mind Centre fosters an environment that supports world leaders in mental health, neuroscience and neurology. Our researchers are supported by strong sydney.edu.au/brain-mind research capabilities, underpinned by a network of shared research facilities in imaging, neuropathology, microscopy and a neurology laboratory. Brain and Mind Centre Annual Report 2015-16

MRI research from Southern Radiology. The University of Sydney Page 58 Imaging Our state-of-the-art imaging facilities span preclinical and clinical imaging, as well as the Sydney Neuroimaging Analysis Centre.

Preclinical imaging Clinical imaging Sydney Neuroimaging Brain and Mind Centre is home Southern Radiology is a leading Analysis Centre to the University of Sydney and provider of radiological services Also housed at Brain and Mind ANSTO Node of the Australian in Sydney, operating a network Centre’s Mallett Street campus is National Imaging Facility. of radiology practices across the the Sydney Neuroimaging Analysis This shared facility provides city, including an imaging research Centre, a cutting-edge facility researchers with access to state- facility at Brain and Mind Centre. that uniquely integrates in-house Technical Facilities of-the-art imaging capabilities This facility houses a state-of-the- neuroimaging research with a for research. The preclinical art 3 Tesla Magnetic Resonance dedicated, regulatory-compliant imaging platform includes Imaging (MRI) scanner, capable commercial image analysis facility micro-PET, PET-CT, PET/SPECT/ of running structural, diffusion, for Phase 2, 3 and 4 clinical CT and 3T MRI scanners as well functional and spectroscopic research trials. as autoradiography, radio- imaging for research as well as metabolite analysis and tissue for patient care. counting facilities. Through our collaboration with Our imaging researchers are Southern Radiology, Brain and focused on developing new Mind Centre researchers have technologies for non-invasive developed a sophisticated imaging and imaging biomarker multinuclear spectroscopy development. We collaborate with program that provides the ability many researchers, both at Brain to image a range of spectroscopic and Mind Centre and overseas, to nuclei. The technique, known as develop new imaging methods and magnetic resonance spectroscopy test new drugs and interventions (MRS), is used to study the for various brain disorders, metabolic changes associated including neurodegenerative with diseases that affect the diseases, mood disorders brain. It also provides additional and cancer. information on top of the structural information that is Our core business Our imaging scientists have an obtained from MRI alone. outstanding track record in preclinical imaging innovation, Our researchers are studying the developing novel technologies for changes that occur in the brain the advancement of neuroimaging as a result of a particular disease, research and understanding of which may ultimately be helpful disease processes. in the clinical diagnosis and treatment of these diseases. Page 59 Neuropathology Microscopy Neurology Laboratory Our extensive expertise in Brain and Mind Centre’s Brain and Mind Centre’s Neurology neuropathology allows us to microscopy facilities provide Laboratory is Australia’s first analyse the molecular and cellular researchers with access to specialised neuromuscular basis of neurological diseases, sophisticated technology to pathology unit. We are one of including brain tumours and observe diseases of the brain and the world’s leading centres for neurodegenerative conditions. mind at a micro level. diagnosis and research into nerve and muscle diseases. In doing so, we can identify new The microscopy facility based ways of diagnosing these disorders at Brain and Mind Centre forms The Neurology Laboratory, when the disease first manifests, part of Sydney Microscopy and a collaboration between the sydney.edu.au/brain-mind allowing patients to benefit from Microanalysis (SMM), the University University of Sydney and Royal the most effective interventions of Sydney’s largest core facility Prince Alfred Hospital, is a available, as early as possible. run by the Australian Centre for state reference laboratory for By increasing our knowledge of Microscopy and Microanalysis. peripheral nerve and muscle the underlying basis of these This cross-disciplinary research histopathology (NATA/RCPA diseases, we can help progress centre is one of the most Accreditation Number 2146). the development of new and more comprehensive microscopy Established in the late 1960s, effective treatments. centres in the world, with the laboratory was the first world-class instrumentation and specialised neuromuscular We are working on developing technical expertise available for pathology unit in Australia. We novel blood tests that enable all researchers. remain one of the world’s leading early detection of major diseases, centres for diagnosis and research including brain tumours and In early 2017, the microscopy into diseases of nerve and muscle. multiple sclerosis. We are also core facility was rolled into the investigating brain tumour University’s core facility: Sydney The laboratory holds one of the tissue to learn more about its Microscopy and Microanalysis largest curated nerve archives in complex genetic makeup and how (SMM). This gives us access to a the world. This repository is an brain tumours manipulate their combined facility management invaluable resource for research surroundings in order to grow. booking system that allows and teaching across brain and

Brain and Mind Centre Annual Report 2015-16 users to seamlessly book any mind sciences. The laboratory has Our neuropathology research microscopy platform across Brain produced more than 300 original program is part of the Royal and Mind Centre, Madsen and the research publications and trained Prince Alfred Department Charles Perkins Centre. numerous PhD and other higher of Neuropathology; the only degree students. neuropathology department in New South Wales that provides specialist diagnostic expertise, including: −− tissue-based diagnostic services for the Royal Prince Alfred Hospital −− a second opinion service for complex cases from across NSW and overseas −− molecular testing services for brain tumours The University of Sydney −− NSW state referral laboratory for Creutzfelt-Jacob Disease (CJD) diagnosis −− autopsy neuropathology −− muscle biopsy pathology. Page 60 Technical Facilities Highlights

In December 2016 the microscopy team were awarded a research portfolio SHINE award from the University of Sydney, recognising their outstanding commitment to partnering with the research community as well as the wider University. Technical Facilities

Research grants Research grants awarded in 2017 awarded in 2016 A system for simultaneous National Imaging Facility (NIF) brain PET and behavioural UNSW Nodes measurements in freely Led by: Meikle, S. moving mice Granting body: NSW Department Led by: Meikle, S. of Industry/Research Attraction Granting body: DVC Research/ and Acceleration Program Bridging Support Grant Years: 2016–19 Years: 2017 Amount: $810,000 Amount: $30,000 A novel scintillating optical Total-body PET technology and fibre array for cancer imaging methods for biological systems and therapy research in metabolic disorders Led by: Kuncic, Z., Vial, P., and mental illness Atakaramians, S. and Meikle, S. Led by: Meikle, S.R. Granting body: Australian and Cherry, S.R. Research Council (ARC)/Linkage Granting body: University Projects (LP) Highlights of Sydney – University of Years: 2015–18 California, Davis Priority Amount: $288,170 Partnership Collaboration Awards Program 2017 PET imaging of learning-related Years: 2017 plasticity in awake behaving rats Amount: $40,000 Led by: Balleine, B., Meikle, S. and Fulton, R. Granting body: Australian Research Council (ARC)/ Discovery Projects (DP) Years: 2016–20 Amount: $995,000 Page 61 Imaging research Neuropathology research Imaging brain behaviour Total-body PET technology and A state-wide centre for In 2015–16, our team used a new methods for biological systems forensic pathology technique for the first time in the research in metabolic disorders In June 2015, Brain and Mind real world. This technique, which and mental illness Centre’s neuropathology service we have developed over the past While PET can probe the became a state-wide forensic 10 years, enabled us to undertake metabolic and signalling pathways pathology service, making us the positron emission tomography underlying chronic disease largest centre for brain autopsy (PET) brain imaging on animals processes, the key questions examination in New South Wales. while they were conscious and in mental illness and diabetes freely moving. This means we can cannot be addressed using single This NSW Health recognition sydney.edu.au/brain-mind study how the brain responds to organ imaging. This proposal consolidates us as a national its environment, what chemical brings the research teams at the centre for expertise alongside changes take place during University of California, Davis NSW Health Pathology and Sydney certain behaviours and how this and the University of Sydney Local Health District. affects disease. together to develop completely new quantitative whole body Next generation sequencing In 2015–16, we collaborated with PET imaging approaches to study In 2016, we acquired a new deep researchers at the University of chronic diseases. sequencer (next generation New South Wales to use this new sequencing technology) to imaging technique to understand Collaborator: Professor diagnose and research diseases the role of dopamine in learning- Simon Cherry, University of of the brain and mind. We can related plasticity. California, Davis. sequence 80 million strands of Funding body: University of DNA at the same time. This means Sydney – University of California, that we can research much more Davis Priority Partnership tailored drug therapies. For Collaboration Awards Program. example, we can now profile a person’s brain tumour to assess them for tailored drug targets and therefore provide patients with

Brain and Mind Centre Annual Report 2015-16 more treatment options. The University of Sydney

Susannah Hallal, Dr Maggie Lee, Dr Kim Kaufman and Associate Professor Michael Buckland (left to right). Page 62 Technical Facilities 2017 and beyond

A centralised laboratory A new centralised laboratory will allow microscopy equipment to be consolidated from across Brain and Mind Centre, to allow better service and guidance from the microscopy technicians.

The laboratory will house all the microscopy systems that are currently Technical Facilities managed by SMM, as well as a newly acquired slide scanner, new analysis computers and new fluorescence microscopes. The facility will also be home to two new confocal systems, which were acquired as part of a NHMRC / University of Sydney grant by Professor Glenda Halliday. One of these systems is optimised for multiparameter fluorescence analysis of slides, while the other is configured for the time-lapse or real time observation of live cells and tissues in culture. 2017 and beyond Page 63 Technical Facilities Key publications

1. Gillam, J., Angelis, G., Kyme, 4. Gillam, J., Angelis, G. and

sydney.edu.au/brain-mind A. and Meikle, S. (2017). Meikle, S. (2016). List-mode Motion compensation image reconstruction for using origin ensembles in positron emission tomography awake small animal positron using tetrahedral voxels. emission tomography. Physics Physics in Medicine and in Medicine and Biology, 62(3), Biology, 61(18), N497-N513. 715-733. 5. Reilhac, A., Charil, A., 2. Barnett, R., Meikle, S. and Wimberley, C., Angelis, Fulton, R. (2016). Cross G., Hamze, H., Callaghan, population motion modeling P., Garcia, M., Boisson, F., applied to attenuation Ryder, W., Meikle, S. and correction of respiratory Gregoire, M. (2015). 4D PET gated F18-FDG PET. IEEE iterative deconvolution with Transactions on Nuclear spatiotemporal regularization Science, 63(1), 170-179. for quantitative dynamic PET imaging. NeuroImage, 118, 3. Cochran, B., Ryder, W., 484-493. Parmar, A., Tang, S., Reilhac, A., Arthur, A., Charil, A., 6. Gholami, Y., Zhu, X., Fulton, Hamze, H., Barter, P., R., Meikle, S., El-Fakhri, G. and Brain and Mind Centre Annual Report 2015-16 Kritharides, L., Meikle, S., Kuncic, Z. (2015). Stochastic Rye, K., et al. (2016). In vivo simulation of radium-223 PET imaging with [18F]FDG dichloride therapy at the to explain improved glucose sub-cellular level. Physics in uptake in an apolipoprotein Medicine and Biology, 60(15), A-I treated mouse model of 6087-6096. diabetes. Diabetologia, 59(9), 1977-1984.

The University of Sydney Page 64 Technical Facilities

Professor Iain McGregor (left) and Associate Professor David Allsop. Page 65 Brain and Mind Centre Our donors

Our transformative work would not be possible without philanthropy. In a climate where it has never been more difficult to secure competitive grant funding for our sydney.edu.au/brain-mind researchers, philanthropy has allowed our innovative research to thrive and importantly, helped to support the future generation of scientific leaders; early-career researchers.

Our focus on translating research When it comes to philanthropy, Unprecedented and monumental into real outcomes that improve the impact our donors have donations such as the Lambert patient care and treatments sets on advancing mental health Initiative are incredible, but us apart from other institutions. and neuroscience research is understandably rare. More As the multidisciplinary home for very significant. 100 per cent of often, donations support the mental health and neuroscience donations received go directly to appointment of specific research at the University of Sydney, we funding innovative research that staff, enabling us to attract the are part of an institution with a may otherwise not be supported best talent from across Australia proven track record of research through traditional grant streams. and the world. Over the last two Brain and Mind Centre Annual Report 2015-16 excellence, which benefits years, we have received more than communities near and far. In fact, $6 million in donations to support the University of Sydney is number research, scholarships and one in Australia for research services across child development impact, according to the 2017 and behaviour, youth mental CWTS Leiden Rankings. health and addiction, and ageing and neurodegeneration. The University of Sydney

Associate Professor Muireann Irish

Page 66 works with a patient. Supporting Early-Career Researchers Philanthropy is vital to funding Donations fund our ECRs’ work The Johnston Fellowship has our Early-Career Researchers across all areas. The Adolf Blasser also supported work in emerging (ECRs). ECRs in the field of mental Charitable Trust has contributed mood disorders by investigating health and neuroscience often $240,000, enabling Joanne hormonal therapy and hormonal struggle to gain the vital research Carpenter to transition from PhD development in young women. experience necessary to win student to research fellow. This Fellowship was established grant funding. in 2014 for two years and was “The generous support of the recently renewed for an additional A philanthropic gift allows ECRs to Adolf Basser charitable trust three years, representing an continue to work in their chosen has allowed me to commence a overall contribution of $625,000. Brain and Mind Centre field without having to turn to post-doctoral position following other research areas where grant the completion of my PhD and to “My family and I consider the funding is perhaps more easily continue building on my previous work The University of Sydney’s available. By supporting career research without stopping to look Brain and Mind Centre does progression and translational for other funding opportunities,” to be of great importance in research, we ensure the best says Joanne. “This has meant I understanding causes and talent is attracted to this field and am able to continue in my area of formulating treatment strategies is advancing research our donors interest and expertise, and I can in the area of mental health,” says care deeply about. focus on extending this important Mr. Johnston. “Its contribution research to provide a deeper to improving mental health will The Bluesand Foundation understanding of the role of the have a significant impact on Scholarship in Alzheimer’s body clock in mood disorders.” outcomes for those affected disease, for example, will provide and the broader community. We $360,000 to support an ECR as a understand first-hand the impact research fellow for the next three hormonal related depression years to undertake translational can have and how important it research in this critical area. is to advance knowledge and services in this area. Through the Johnston Fellowship we hope to also encourage more promising researchers and clinicians to pursue this important area, helping further develop the Brain Our donors and Mind Centre to achieve all it can in serving future generations.”

“Bluesand Foundation has long supported Alzheimer’s research and we were motivated by both personal experience and our confidence in the University’s ability to conduct this important research. We are excited by the work the Brain and Mind Centre is now leading and are pleased to be supporting the next generation of research leaders in this field, who will be critical to advancing this research and making significant breakthroughs.”

Bluesand Foundation Page 67 High impact philanthropy One of the largest philanthropic “Our move to a more donations over the last two years interdisciplinary method of has come from a private family to working will place more focus on establish the Kam Ling Barbara examining the links and similarities Lo Chair in Neurodegenerative between neurodegenerative Disorders. This $1.5 million diseases such as Parkinson’s and commitment will help to establish a Motor Neurone Disease and will new Chair in translational research significantly contribute to our

sydney.edu.au/brain-mind for the next five years. A Chair is already important work in ageing the pinnacle of research, and is the and neurodegeneration.” most effective way of transforming research and its culture, as The appointment of the Kam Professor Matthew Kiernan, Ling Barbara Lo Chair and a the current Bushell Chair of team specifically focused in this Neurology, has done so effectively. direction will allow for a significant “Philanthropic donations are vital increase in the Brain and Mind at every level. From supporting Centre’s combined efforts to a PhD student to fully funding a combat disorders of the brain and Chair position, these gifts allow us mind by generating high impact to continue our work but also to research that translates into expand into areas of new focus and improving patient outcomes. attract the best talent to be able to do this,” says Professor Kiernan. “This new chair, generously funded for the next five years, will enable the Centre to double down on its efforts in finding effective treatments for diseases such as Parkinson’s and Motor Neurone

Brain and Mind Centre Annual Report 2015-16 Disease, as well as bring a more strategic approach to the research.”

Professor Matthew Kiernan Bushell Chair of Neurology The University of Sydney

Professor Ian Hickie, Professor Jane Burns and Dr Laura Ospinas demonstrate Project Synergy to the Prime Minister Malcolm Turnbull and former Minister for Health Sussan Ley. Page 68 Measuring impact, working for outcomes Thanks to our donors There has never been a more The Brain and Mind Centre The Yulgibar Foundation, John and promising time to support mental wishes to thank all of our donors. Catherine McCabe, Mrs Rae health and neuroscience research. Your generosity keeps our work Cottle, Mr Ian William Jew, The advancements that will possible and together we raised Meeting for Minds Charitable emerge in this field over the next over $6 million in donations Foundation, Dr Jill M Hawker, five to ten years in particular will June 2015-June 2017. Cecil and Richard Churm transform knowledge and practice (OBEMs), Michaella Dupont- and ultimately help to improve No gift is too small and we Louis, Mrs Christine Windeyer, outcomes for patients and their welcome contributions of any size. Mr Alastair Griffin, Hunters families. Philanthropy will remain We wish to particularly thank the Hill Quilters, Estate of the late an essential part of our success following people who donated Santiago Vasco, Macquarie Group and ability to realise these $1000 or more. Thank you too to Foundation, Mr Heath McLaren, breakthroughs and discoveries. all our donors who wish to remain Mr Robert Luciano, Parkinsons anonymous and to all those who ACT Incorporated, Mr Craig We deeply value relationships have contributed over the last Whitworth, Mr David E Landa with all supporters and partners two years. (OAMMs), Debbie and Zac Seidler, who understand the role that Patricia and Grae McKenzie, Brain and Mind Centre high-quality, multidisciplinary ClubsNSW, The Garnett Passe Mrs Anne Osborne Sullivan, and translational research plays and Rodney Williams, Memorial Craig and Suzanne Whitworth, alongside clinical services in Foundation, Estate of the Late Follow the Seed Australia driving real outcomes. The impact Christopher J Wood, Mr Michael Pty Ltd, Mrs Cveta Lillyman, of their support is immeasurable R Johnston, Bluesand Foundation University of Sydney Union, ROAM and increasingly pivotal to Pty Ltd, St Vincent’s Private Communities, Ms Elaine Chang, our success. Hospital Sydney, Adolph Basser Conversely, Mrs Hilary Marion Charitable Trust, The Mill House Cairns, Ms Eleanor Sydney-Jones, To find out more about how you Foundation, Future Generation Dr Steven K C Lee, Mr Robert can support our work, please visit Investment Company, Dr Eleanor Phillips, Dr Marion G Maxwell, −− sydney.edu.au/brain-mind/ Jew, Southern Scene Pty Limited, Dr Doug Wilkins, Dr Jean Palmer, donate Mrs Helen Breekveldt, Liberty Ms Mimi Le, Mr Ian Boyd, Ms Lesley International Underwriters, Bradley, Mr Robert A Johnston, Breekveldt Holdings Pty Ltd, AC Monte Sant Angelo College, Mr Fred Street (AM), Joseph and Mr Leslie P Pongrass, Ms Diane Clara Vucetic, Harper Bernays Chaffey, Ms Cara Chriqui, Charitable Trust, Parkinson’s Ms Susan Fielding, Mrs Bunny Society of the Gold Coast Inc., Gardiner-Hill, Mr Miles Prosser. Our donors Page 69 Brain and Mind Centre Our teams

Our unique teams consist of academics, researchers, students and professional staff. They are the lifeblood of Brain and Mind Centre. We acknowledge and give thanks sydney.edu.au/brain-mind for their tireless hard work, diligence and dedication to their research, which can, and is, changing the world.

The Child Development and Behaviour Team Academic staff −− Dr Antoinette −− Shrujna Patel −− Professor Mark Dadds, Redoblado-Hodge, −− Elizabeth Nguyen Clinical Neuropsychologist NHMRC Principal Research −− Zahava Ambarchi Fellow and Professor of −− Dr Sonia Sultan, Senior −− Eleni Demitriou Psychology, Team Leader Clinical Psychologist −− Shin Ho Park −− Professor Adam Guastella, −− Dr Christine Song, Principal Research Fellow Postdoctoral Research Fellow −− Karen Lesley Pepper Brain and Mind Centre Annual Report 2015-16 Psychiatry, Team Leader −− Dr Lucy Tully, Honours students −− Associate Professor Senior Project Leader −− Tooba Zaidi David Hawes, −− Antonio Mendoza-Diaz, Associate Professor of Postdoctoral Researcher Psychology, Team Leader Masters students −− Dr Christina Thai, −− Dr Rinku Thapa −− Associate Professor Clinical Psychologist Natalie Silove, −− Dr Patrycja Piotrowska, Clinical Associate Professor, Professional staff Postdoctoral Researcher Paediatrics and Child Health −− Tiffany Sia, Research Assistant −− Professor Russell Dale, PhD students Professor of Paediatric −− Emma Thomas, −− Bridie Leonard Neurology Child Assessment Lead −− Jaimie Northam −− Dr Meryn Lechowicz, Senior −− Dr Alice Norton, Clinical Clinical Psychologist −− Carrie Fisher Research Manager −− Dr Fran Doyle, Senior −− Kim McGregor −− Dr Rothanthe Georgiou, Project Leader −− Marilena Demayo Clinical Trial Coordinator The University of Sydney −− Anne Masi −− Dr Izabella Pokorski, Clinical Trial Coordinator Page 70 The Youth Mental Health Team Academic staff Professional staff PhD students −− Professor Ian Hickie, −− Ms Lisa Whittle, −− Frank Iorfino Program Leader Research Product Manager −− Ashleigh Tickell −− Professor Jane Burns, −− Ms Alyssa Milton, −− Jeanne Gehue Senior Academic Post-Doctoral Research fellow −− Joanne Carpenter −− Associate Professor −− Ms Candace Brennan, −− Ashlee Grierson Daniel Hermens, Office Manager −− Peta Eggins Head of Neurobiology stream −− Ms Sarah Piper, −− Ms Tracey Davenport, Research Officer −− Casey Paquola Head of Technology stream −− Mr Django White, −− Dr Laura Ospina-Pinillos −− Mr Shane Cross, Research Coordinator −− Vanessa Cheng Head of Clinical Services and Data Manager −− Cate McHugh Development Stream −− Ms Amelia English, −− Kate Chitty −− Professor Adam Guastella, Senior Project Officer −− Ange Weinrabe Senior Clinical Researcher −− Ms Natalia Zmicerevska, −− Jacob Crouse

−− Professor Sharon Naismith, Research Psychologist Brain and Mind Centre Senior Neuropsychologist −− Ms Alissa Nichles, Honours students −− Associate Professor Clinical Research Officer −− Sophia Bogaty Louise Nash, Post-graduate Education Academic and −− Professor Niels Buus, professional collaborators Suicide intervention −− Professor Nick Martin −− Professor Sally Cripps, −− Professor Paul Amminger Bayesian statistics −− Professor Cheryl Jones −− Professor Jim Lagopoulos, Neuroimaging expertise −− Professor Simon Carlile −− Professor Richard Banati, −− Mr John Mendoza Neuroimaging expertise −− Professor Pat McGorry −− Professor Jan Scott −− Professor Kathleen Merikangas Our teams Page 71 The Psychology Clinic Academic staff −− Jennifer Read Masters students −− Associate Professor −− Elizabeth Stewart −− Stefan Bogdanov Maree Abbott, Director −− Jemma Todd −− Lucy Braude of Clinical Training −− Ruth Wells −− Melanie Brookes −− Ms Shylaja Gooley, Director −− Elpiniki Andrew −− Nadine Devaki-Wright Psychology Clinic −− Sarah Leila Barakat −− Renata Hadzic −− Professor Caroline, Hunt Head Clinical Psychology Unit −− Rachel Brownlow −− Samantha Joplin −− Professor Stephen Touyz, −− Virginia Burgdorf −− Cassandra Joslyn sydney.edu.au/brain-mind Clinical Professor −− Carri Ann Fisher −− Aspasia Karageorge −− Ms Frances Gibson, −− Daniel Forrest −− Daniel Kimber Clinical Psychologist −− Danielle Gessler −− Daria Kouznetsova −− Ms Katy O’Neill, −− Lauren Harvey −− Meredith Medway Clinical Psychologist −− Emma Jones −− Khai Sng −− Dr David Horry, Psychologist −− Brittany Killer −− Jo-Elle Stein −− Associate Professor David Hawes −− Cecilia Law −− Valerie Yeung −− Associate Professor Sunny Lah −− Bridie Leonard −− Sarah Barrett Jones −− Associate Professor −− Rachel Menzies −− Emily Bartlett Paul Rhodes, −− Belinda Poole −− Rachel Barton −− Ms Chantal Braganza, Clinical Psychologist −− Amy-Lee Sesel −− Melissa Blair −− Professor Louise Sharpe, −− Stephanie Tesson −− Alison Clark PG Coordinator −− Shannon Webb −− Katherine Dobinson

PhD students −− Julia White −− Michelle Edwards −− Amy Leigh Burton −− Michael Zhang −− Gavin Entwistle −− Matteo Zuccala −− Michael Fitzpatrick

Brain and Mind Centre Annual Report 2015-16 −− Jaymee-Lee Chebli −− Elizabeth (Liza) Chervonsky −− Brooke Adam −− Gracie Garber −− Sarah Ellis −− Phillip Aouad −− Bree Gregory −− Rosanna Francis −− Cate Broomfield −− Emma Lamph −− Catherine (Katie) Gittins −− Madeleine Ferrari −− Ben Larke −− Andreea Heriseanu −− Jennifer Malecki −− Ursula Legoe −− Ben Huntingdon −− Eileen Seah −− Roisin Lynch −− Alice Lo −− Chloe McGrath −− Lucinda Mairs −− Sharlene Mantz −− Nahian Chowdhury −− Gregory Martin −− Claire Mcaulay −− Rose Iannuzzelli −− Kristie McDonald −− Kimberley Mcgregor −− Amelia Scott −− Teleri Moore −− Matthew Modini −− Zac Seidler −− Alicia Moss −− Melissa Noetel (Fietz) −− Alison Clark −− David Muir −− Angelique (Angie) Ralph −− Claudia Nielson-Jones −− Nurul Praharso The University of Sydney −− Greg Quartly-Scott −− Imogen Richards −− Ran Shi −− Avalon Tissue −− Megan Turnbull Page 72 The Gambling Treatment and Research Clinic

Professional staff Academic and professional staff −− Miss Suzanna Azevedo, Research −− Professor Alex Blaszczynski −− Hanna Kallenberg, Assistant/ MCP Candidate Director, Gambling Clinic Provisional Psychologist −− Ms Brittany Ager, Research −− Dr Fadi Anjoul, Deputy Director −− Trisha Knowland, Assistant DCP/MSc Student and Clinical Psychologist Provisional Psychologist −− Ms Louise Bezzina, Research −− Dr Sally Gainsbury, −− Sarah Rees, Provisional Assistant, MCP Candidate Deputy Director, Research Psychologist −− Ms Olivia Schollar-Root, −− Ms Kirsten Shannon, −− Michelle Beckett, Research Assistant, Psychologist and Manager Project Manager MCP Candidate −− Christopher Hunter, −− Miss Brittany Keen, −− Ms Belinda Ingram, Education Clinical Psychologist and Research Assistant/ Support Officer Clinical Supervisor PhD Candidate −− Ms Cindy Li, −− Janine Bleakley, Psychologist −− Mr Dylan Pickering, Administrative Assistant −− Martin Wierczorek, Research Assistant/ PhD Candidate −− Ms Layal Haydar, Psychology Psychologist

Clinic Receptionist −− Ms Jennifer Molinari, −− Jessica Lam, Research Assistant Brain and Mind Centre Psychologist −− Elle Formica, Intake Officer −− Ms Kerrie Macalister, Provisional Psychologist Our teams Page 73 The Neuroimmunology Team Multiple Sclerosis

−− Associate Professor Academic staff PhD students Fabienne Brilot-Turville, −− Associate Professor Michael −− Heidi Beadnall Principal Research Fellow Barnett, Team Leader −− Joshua Barton −− Professor Russell Dale, −− Emeritus Professor John −− Mahtab Ghadiri Paediatric Neurologist Pollard, Professor of Neurology, −− Chenyu (Tim) Wang −− Professor David Brown, MS clinician and researcher −− Saeideh Ebrahimkhani Immunologist −− Professor Simon Hawke, −− Professor Steve Vucic, Jessie Alberti Senior Students – Engineering/ Neurologist Principal Research Fellow IT and BMC sydney.edu.au/brain-mind −− Dr Melanie Wong, Senior −− Associate Professor −− Scott Lill staff specialist in paediatric Stephen Reddel, Associate −− Suman Regmi allergy & immunology Professor Neurology, −− Antonio Lopes −− Dr Sudarshini Ramanathan, neuroimmunology clinician −− Scott Lill Neurologist −− Associate Professor −− Mayisha Khan −− Professor David Booth, Weidong (Tom) Cai Principal Research Fellow −− Dr Judith Spies, Honours students −− Professor Graeme MS clinician/researcher −− Antonio Clark Stewart, Clinical Professor −− Dr Jane Frith, MS of Immunology clinician/researcher −− Professor Matthew Kiernan, −− Dr Todd Hardy, MS Bushell Chair of Neurology clinician/researcher −− Dr Emily Mathey, −− Dr Linda Ly, Postdoctoral Researcher postdoctoral researcher −− Professor Michael −− Dr Sidong Liu, Barnett, Neurologist postdoctoral researcher −− Associate Professor Stephen −− Ms Caitlin Dawes, psychologist

Brain and Mind Centre Annual Report 2015-16 Reddel, Neurologist Professional staff −− Associate Professor Michael −− Dr Marinda Taha, clinical Buckland, Neuropathologist trials coordinator −− Associate Professor −− Miss Ishana Dixit, William Phillips, Physiologist research assistant −− Professor Stephen Adelstein, −− Miss Deleni Walters, Clinical immunologist research assistant −− Dr Nicolas Urriola, −− Ms Annemarie O’Connell, Clinical immunologist research nurse/clinical −− Associate Professor Clare nurse consultant Fraser, Neuro-opthalmologist MS Fellow −− Professor Ian Hickie, Professor of Psychiatry −− Dr Justin Garber −− Dr Susanna Park, Physiologist The University of Sydney Page 74 ForeFront Ageing and Neurodegeneration Team Academic staff −− Professor Sharon Naismith, −− Professor Michael Kassiou −− Professor Glenda Halliday, Leonard P Ullman Chair in Professor of Medicinal NHMRC Senior Principal Psychology, team leader Chemistry ForeFront Research Fellow, Professor of Healthy Brain Ageing Program imaging & drug design Neuroscience, team leader −− Professor Jillian Kril, −− Professor Victor Villemagne, ForeFront Dementia and Professor of Neuropathology Professor of Medicine Movement Disorder Laboratory ForeFront Dementia and ForeFront imaging −− Associate Professor John Movement Disorder Laboratory −− Professor John Magnussen, Kwok, Research geneticist, −− Dr Claire Shepherd, Professor of Neuropathology team leader ForeFront Director and Facility Manager ForeFront imaging Neurogenetics and Epigenetics ForeFront Dementia and −− Professor John Mattick, Research Group Movement Disorder Laboratory Professor of Molecular Biology −− Professor Matthew −− Professor Stanley Prusiner, ForeFront RNA biology Kiernan, Bushell Chair of Professor of Neurology and −− Professor Antony Neurology, team leader Biochemistry ForeFront Cooper, Professor of ForeFront Motor Neurone Dementia and Movement Neuropathology Forefront

Disease Research Group Disorder Laboratory Neurodegeneration Research Brain and Mind Centre −− Professor Steve Vucic, −− Professor Ian Blair, Professor Laboratory/RNA biology Professor of Neurology of Neuroscience ForeFront −− Dr Dominic Hare, Chancellor’s ForeFront Motor Neurone Neurogenetics and Epigenetics Postdoctural Research Fellow Disease Research Group Research Group Forefront Neurodegeneration −− Professor John Hodges, −− Professor Rosa Rademakers, Research Laboratory Professor of Cognitive Professor of Neuroscience −− Associate Professor Neurology, team leader ForeFront Neurogenetics and David Finkelstein, Senior Frontier Frontotemporal Epigenetics Research Group Research Fellow Forefront Dementia Research Group −− Dr Jonathon Rohrer, MRC Neurodegeneration −− Professor Olivier Piguet, Clinician Scientist ForeFront Research Laboratory NHMRC Senior Research Frontier Frontotemporal −− Associate Professor Woojin Fellow, Professor of Dementia/Neurogenetics Scott Kim, Neuroscientist in Neuropsychology, team leader and Epigenetics molecular biology, animal Frontier Frontotemporal −− Professor Amy Brodtmann, models and translation Dementia Research Group Professor of Stroke and ForeFront Dementia and −− Professor Simon Lewis, Cognitive Neuroscience Movement Disorder Laboratory NHMRC Dementia Research Frontier Frontotemporal −− Dr Carol Dobson-Stone, Senior Fellow, Professor of Cognitive Dementia Research Group Research Fellow and geneticist Neurology, team leader −− Professor Dominic Rowe, ForeFront Dementia and ForeFront Parkinson’s Disease Professor of Neurology Movement Disorder Laboratory and Dementia with Lewy ForeFront Motor Neurone −− Dr Nicolas Dzamko, NHMRC CJ Our teams Bodies Research Group Disease/Parkinson’s Disease Martin Fellow and biochemist −− Professor Carolyn Sue, −− Professor Ian McKeith, ForeFront Dementia and Professor and Director of Professor of Old Age Psychiatry Movement Disorder Laboratory Neurogenetics, team leader ForeFront Parkinson’s Disease −− Dr Yuhong Fu, Senior Research Genetics of Parkinson’s Disease and Dementia with Lewy Fellow ForeFront Dementia and −− Associate Professor Kay, Bodies Research Group Movement Disorder Laboratory Double Associate Professor −− Professor Lars Ittner, −− Dr Susanna Park, Senior of Neuroscience, team leader Professor of Medicine Lecturer ForeFront Forefront Neurodegeneration ForeFront animal modelling Motor Neurone Disease Research Laboratory −− Dr Yasi Ke ARC Research Fellow Research Group ForeFront animal modelling Page 75 −− Associate Professor Muireann −− Dr Emily Mathey, Research −− Dr Ramon Landin-Romero, Irish, ARC Future Fellow Fellow ForeFront Research Fellow and and neuropsychologist Motor Neurone Disease neuroimagery Frontier Frontier Frontotemporal Research Group Frontotemporal Dementia Dementia Research Group −− Dr Neil Simon Neurologist Research Group −− Dr Jin-Sung Park Senior ForeFront Motor Neurone −− Tooba Zaidi, Research Research Fellow Genetics Disease Research Group Administration Officer of Parkinson’s Disease −− Dr Tim Howells Research Frontier Frontotemporal −− Dr Kishore Kumar, Clinical Officer and neurophysiologist Dementia Research Group Senior Lecturer Genetics ForeFront Motor Neurone −− Dr Claire O’Callaghan, of Parkinson’s Disease Disease Research Group NHMRC CJ Martin Fellow sydney.edu.au/brain-mind −− Dr Mac Shine, NHMRC CJ −− Dr Rebekah Ahmed, and neuropsychologist Martin Fellow, neurologist NHMRC Early Career Fellow ForeFront Parkinson’s Disease and neuroimagery ForeFront and neurologist Frontier and Dementia with Lewy Dementia and Movement Frontotemporal Dementia Bodies Research Group Disorder Laboratory Research Group and −− Dr Kaylena Ehgoetz Martens, −− Dr Rachel Tan, Dementia Motor Neurone Disease Postdoctural Research Fellow Research Fellow and Research Group ForeFront Parkinson’s Disease neuroscientist ForeFront −− Dr Kazumoto Shibuya, and Dementia with Lewy Dementia and Movement Neurologist and visiting scholar Bodies Research Group Disorder Laboratory ForeFront Motor Neurone −− Dr Elie Matar, Training −− Dr Sivaraman Purushothuman, Disease Research Group Neurologist ForeFront Dementia Research Fellow −− Dr Nortina Shahrizaila, Parkinson’s Disease and and neuroscientist ForeFront Neurologist and visiting scholar Dementia with Lewy Dementia and Movement ForeFront Motor Neurone Bodies Research Group Disorder Laboratory Disease Research Group −− Dr Ryan Davis, NHMRC Early −− Dr Surabhi Bhatia, Dementia −− Dr Jose Manuel Matamala, Career Fellow and neurologist Research Fellow and Neurologist and visiting scholar Genetics of Parkinson’s Disease neuroscientist ForeFront ForeFront Motor Neurone −− Dr Brian Koentojoro,

Brain and Mind Centre Annual Report 2015-16 Dementia and Movement Disease Research Group Research Fellow Genetics Disorder Laboratory −− Dr Parvathi Menon, Neurologist of Parkinson’s Disease −− Dr Katherine Phan, ForeFront Motor Neurone −− Dr Ariadna Recasens, Postdoctural Research Fellow Disease Research Group Research Fellow Genetics ForeFront Dementia and −− Dr Nimeshan Geevasinga, of Parkinson’s Disease Movement Disorder Laboratory Neurologist ForeFront −− Dr Gautam Wali, Associate −− Dr Sharpley Hsieh, NHMRC Motor Neurone Disease Lecuturer Genetics of Dementia Research Fellow Research Group Parkinson’s Disease and neuropsychologist −− Dr James Burrell, NHMRC Early −− Dr Shantel Duffy, Dementia ForeFront Motor Neurone Career Fellow and neurologist Research Fellow and Disease Research Group Frontier Frontotemporal neuroscientist Healthy −− Dr Michael Lee, OSMR Postdoc Dementia Research Group Brain Ageing Program Fellow and physiotherapist −− Dr Cristian Leyton Moscoso, −− Dr Angela D’Rozario, ForeFront Motor Neurone Dementia Research Fellow Dementia Research Fellow Disease Research Group and neurologist Frontier and neuroscientist Healthy −− Dr William Huynh, Postdoctoral Frontotemporal Dementia Brain Ageing Program Fellow and neurologist Research Group −− Dr Camilla Hoyos, Dementia The University of Sydney ForeFront Motor Neurone −− Dr Fiona Kumfor, NHMRC Research Fellow and Disease Research Group Dementia Research Fellow neuroscientist Healthy −− Dr Emma Devenney, and neuropsychologist Brain Ageing Program Postdoctoral Fellow and Frontier Frontotemporal −− Dr Loren Mowszowski, neurologist ForeFront Dementia Research Group Dementia Research Fellow Motor Neurone Disease and neuroscientist Healthy Research Group Brain Ageing Program Page 76 −− Dr Negar Memarian, −− Dr Jerome Ip, Neurologist −− Gayaturi Perera, Research Postdoctoral Research and visiting scholar Healthy Assistant, ForeFront Associate Healthy Brain Brain Ageing Program Dementia and Movement Ageing Program −− Dr Catriona Ireland, Disorder Laboratory −− Tenielle Clinch, Genetic Geriatrician and visiting scholar −− Shikara Keshiya, Research Counsellor ForeFront Healthy Brain Ageing Program Assistant, ForeFront Neurogenetics and −− Dr Boris Guennewig, DINAD Dementia and Movement Epigenetics Research Group/ Bioinformatician Healthy Disorder Laboratory Frontier Frontotemporal Brain Ageing Program −− Dr Yue Yang, Research Assistant, Dementia Research Group −− Dr Haley LaMonica, Clinical ForeFront Dementia and −− Elle Elan, Genetic Counsellor Neuropsychologist Healthy Movement Disorder Laboratory ForeFront Neurogenetics and Brain Ageing Program −− Eleanor Ramsey, Research Epigenetics Research Group −− Dr Zac Chatterton Lecturer Coordinator, ForeFront −− Professor Michael Fulham, ForeFront Dementia Motor Neurone Disease Neurologist and RPAH PET and Movement Disorder Research Group Imaging ForeFront Imaging Laboratory/Neurogenetics and −− Dianne Tyson, Executive −− Dr Yu-ichi Noto, Neurologist Epigenetics Research Group Assistant, ForeFront and visiting scholar Motor Neurone Disease Brain and Mind Centre ForeFront Motor Neurone Professional staff Research Group Disease Research Group −− Heidi Cartwright, Forefront −− Margie Zoing, MND Clinical −− Dr Smriti Agarwal, Neurologist Coordinator/SRA, ForeFront Nurse Consultant, ForeFront and visiting scholar Dementia and Movement Motor Neurone Disease ForeFront Motor Neurone Disorder Laboratory Research Group Disease Research Group −− Dr Jude Amal-Raj, Team −− Nicollette Thornton, Clinical −− Dr. Jun Tsugawa, Neurologist Coordinator, ForeFront Trials and Clinic Coordinator, and visiting scholar Dementia and Movement ForeFront Motor Neurone ForeFront Motor Neurone Disorder Laboratory Disease Research Group Disease Research Group −− Thomas Cunningham, −− Tiffany Li, Research Assistant, −− Dr Yan Ma, Neurologist and Database Manager, ForeFront ForeFront Motor Neurone visiting scholar ForeFront Dementia and Movement Disease Research Group Motor Neurone Disease Disorder Laboratory −− David Foxe, Senior Research Group −− Ashneeta Kumar, DINAD Research Officer, Frontier −− Dr. Yoshimitsu Shimatani, Participant Coordinator, Frontotemporal Dementia Neurologist and visiting scholar ForeFront Dementia and Research Group ForeFront Motor Neurone Movement Disorder Laboratory −− Dr Leone Chare, Disease Research Group −− Marianne Hallupp, Laboratory Research Officer, Frontier −− Dr Nick Cordato, Geriatrician, Manager/SRA, ForeFront Frontotemporal Dementia neurologist and visiting scholar Dementia and Movement Research Group Frontier Frontotemporal Disorder Laboratory

−− Nicole Mueller, Frontier Our teams Dementia Research Group −− Eve Jary, Research Assistant, Donor Coordinator, Frontier −− Cassandra Kaizik, Research ForeFront Dementia and Frontotemporal Dementia Assistant/Occupational Movement Disorder Laboratory Research Group Therapist Frontier −− Nikita He, Research Assistant, −− Angela Scharfenberg, Frontotemporal Dementia ForeFront Dementia and Research Assistant, Frontier Research Group Movement Disorder Laboratory Frontotemporal Dementia −− Chengtao Liang, Research −− Dr Farzaneh Atashrazm, Research Group Assistant Frontier Research Assistant, ForeFront −− Kelly Nicholas, Research Frontotemporal Dementia Dementia and Movement Coordinator, Frontier Research Group Disorder Laboratory Frontotemporal Dementia −− Dr Karen Crawley, General Research Group Practitioner Genetics of Parkinson’s Disease Page 77 −− Sarah Homewood, Frontier −− Caitlin Dawes, General −− Rosi Hutchings, Frontier Clinic Administration Assistant, Psychologist, Healthy Frontotemporal Dementia Frontier Frontotemporal Brain Ageing Program Research Group Dementia Research Group −− Kahala Dixon, Research −− Sherry Chen, Frontier −− Jessica Hazelton, Research Nurse/Assistant, Healthy Frontotemporal Dementia Assistant, Frontier Brain Ageing Program Research Group Frontotemporal Dementia −− Claire Burrows, Healthy −− Jill Long, Frontier Research Group Brain Ageing Program Frontotemporal Dementia −− Annu Mothakunnel, −− Stacey West, Research Research Group Research Assistant, Frontier Assistant, Healthy Brain −− Nikki-Anne Wilson, Frontier Frontotemporal Dementia

sydney.edu.au/brain-mind and Ageing Program Frontotemporal Dementia Research Group Research Group −− Cynthia Murray, Research PhD students −− Sicong Tu, Frontier Assistant, Frontier −− Guinevere Lourenco, ForeFront Frontotemporal Dementia Frontotemporal Dementia Dementia and Movement Research Group Research Group Disorder Laboratory −− Stephanie Wong, Frontier −− Nathan Bradshaw, Research −− Tony Hsiao, ForeFront Frontotemporal Dementia Assistant, Frontier Dementia and Movement Research Group Frontotemporal Dementia Disorder Laboratory −− Claire O’Connor, Frontier Research Group −− Ye Zhao, ForeFront Frontotemporal Dementia −− Lucie Bahron, Research Dementia and Movement Research Group Assistant, Frontier Disorder Laboratory −− Siddarth Ramanan, Frontier Frontotemporal Dementia −− Noman Bakhshi, ForeFront Frontotemporal Dementia Research Group Dementia and Movement Research Group −− Stephanie Wong, Research Disorder Laboratory −− Cheng Liang, Frontier Assistant, Frontier −− Jianqun Gao, ForeFront Frontotemporal Dementia Frontotemporal Dementia Dementia and Movement Research Group Research Group Disorder Laboratory −− Cherie Strikwerda-Brown, −− Mirelle D’Mello, Research −− Diba Rastegar, ForeFront Frontier Frontotemporal Brain and Mind Centre Annual Report 2015-16 Assistant, Frontier Dementia and Movement Dementia Research Group Frontotemporal Dementia Disorder Laboratory Research Group −− Emma Johnson, Frontier −− Dr Thanuja Dharmadasa, Frontotemporal Dementia −− Tooba Zaidi, Research PhD student and neurologist, Research Group Administration Officer, ForeFront Motor Neurone Frontier Frontotemporal −− Andi Musrah, Frontier Disease Research Group Dementia Research Group Frontotemporal Dementia −− Dr Nidhi Garg, PhD student Research Group −− Zoe-Lee Goldberg, Frontier and neurologist, ForeFront Research Assistant, Frontier −− Adam Vujic, Healthy Motor Neurone Disease Frontotemporal Dementia Brain Ageing Program Research Group Research Group −− Jennifer Szeto, ForeFront −− Jashelle Caga, PhD student −− Deborah Hammond, Specialist Parkinson’s Disease and and health psychologist, Nurse, ForeFront Parkinson’s Dementia with Lewy ForeFront Motor Neurone Disease and Dementia with Bodies Research Group Disease Research Group Lewy Bodies Research Group −− Moran Gilat, ForeFront −− Hannah Timmins, ForeFront −− Veronica Cottam, Research Parkinson’s Disease and Motor Neurone Disease Assistant and Laboratory Dementia with Lewy The University of Sydney Research Group Manager, ForeFront Bodies Research Group Neurodegeneration −− Elizabeth Highton- −− Christina Liang, Genetics of Research Laboratory Williamson, PhD student Parkinson’s Disease Nick Blair, and MND donor coordinator, −− Alice Gibson, Postdoctoral Genetics of Parkinson’s Disease ForeFront Motor Neurone Research Associate, Healthy −− Kate Ahmad, Genetics of Disease Research Group Brain Ageing Program Parkinson’s Disease Page 78 −− Christine Wools, Genetics Masters students of Parkinson’s Disease −− Dr Alexis de Roquemaurel, −− Jason Gu, Genetics of Neurodegeneration Parkinson’s Disease Research Laboratory −− Isabel Yeap, Genetics of −− Dr Dev Nathani, Masters Parkinson’s Disease student and medical officer, −− Benjamin Trist, ForeFront Motor Neurone Neurodegeneration Disease Research Group Research Laboratory −− Sian Genoud, Neurodegeneration Research Laboratory −− Kathryn Mathews, Neurodegeneration Research Laboratory −− Eurwin Suryana, Neurodegeneration

Research Laboratory Brain and Mind Centre −− Karl Aoun, Neurodegeneration Research Laboratory −− Nathan Cross, Healthy Brain Ageing Program −− Jake Palmer Healthy Brain Ageing Program −− Johannes Michaelian, Healthy Brain Ageing Program −− Madeleine Andrews, Healthy Brain Ageing Program −− Natasha Gabay, Healthy Brain Ageing Program −− Bradley Skinner, Healthy Brain Ageing Program −− Jonathon Pye, Healthy Brain Ageing Program −− Carla Haroutonian, Healthy Brain Ageing Program

Honours students Our teams −− Terence Wong, Neurodegeneration Research Laboratory −− James Carrick, Healthy Brain Ageing Program −− Alice Tricks, Healthy Brain Ageing Program

Page 79 The Technical The Lambert Initiative Facilities Team Academic staff Master students Professional staff −− Professor Iain McGregor, −− Oliver Tan −− Ms Janelle Wright, Team Leader −− Marieke Graat Animal Facility Officer −− Associate Professor David −− Mr Vince Zappala, Allsop, Associate Clinical Honours students Animal Technician Director, Lambert Initiative −− Joel Raymond −− Ms Debbie Brookes, Assistant for Cannabinoid Therapeutics −− Sara Scott Animal Technician −− Associate Professor Jonathon sydney.edu.au/brain-mind −− Hannah Gutmann −− Mr Mark Elgario, Assistant Arnold, Associate Director, Animal Technician Preclinical Research −− Cilla Zhou −− Mrs Sylvia Lohrengel-Kuhner, −− Sarah Abelev −− Dr Michael Bowen, NHMRC Administration Manager, Sydney Peter Doherty Fellow −− Charlotte Fletcher Imaging Core Research Facility −− Dr Lyndsey Anderson, −− Dr Govinda Poudel, Senior Professional staff Research Fellow Technical Officer, Clinical, −− Dr Anjali Bhardwaj, −− Ms Kristin Anderson, Sydney Imaging CRF Executive Officer Research Fellow −− Dr Michael Kuligowski, −− Dr Jordyn Stuart, −− Dr Natalie Elias, Senior Technical Officer Executive Officer Postdoctoral Research Fellow −− Dr Pamela Young, −− Dr Miguel Bedoya Perez, −− Ms Cheryl Handford, Professional Officer: Light Postdoctoral Research Laboratory Manager and Optical Microscopist Associate in Behavioural −− Miss Jessica Gugusheff, and Chemical Ecology Research Assistant −− Mr Richard Kevin, PhD students Research Assistant −− Dilara Bahceci −− Miss Bianca Wilson, −− Natalia Brzozowska Research Assistant Brain and Mind Centre Annual Report 2015-16 −− David Clarke −− Dr Marika Heblinski, −− Kristie Smith Research Associate −− Stephanie Todd −− Mr Jia Luo, Research Associate −− Thomas Arkell −− Ms Anastasia Suraev, Research Associate −− Miss Eila McGregor, Volunteer −− Mr Victor Trevino, Volunteer −− Mr Ivan Low, Research Assistant The University of Sydney Page 80 sydney.edu.au The University of Sydney

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Produced by The Brain and Mind Centre, the University of Sydney, September 2017. The University reserves the right to make alterations to any information contained within this publication without notice.