The efficacy of vortioxetine in adult patients with a recurrent major depressive episode (MDE) A randomized, double-blind, placebo-controlled study McIntyre, R.; Lophaven, S. N.; Olsen, C. K. Published in: International Journal of Neuropsychopharmacology DOI: 10.1017/S1461145714000741 Publication date: 2014 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): McIntyre, R., Lophaven, S. N., & Olsen, C. K. (2014). The efficacy of vortioxetine in adult patients with a recurrent major depressive episode (MDE): A randomized, double-blind, placebo-controlled study. International Journal of Neuropsychopharmacology, 17, 136. https://doi.org/10.1017/S1461145714000741 Download date: 10. Sep. 2020 1 Plenary Lectures Monday 23 June 2014 system activity may have therapeutic potential in almost all diseases affect- ing humans, including ...neurodegenerative, inflammatory,.... pain, ... psychiatric disorders, amongst many others “–as stated in a recent review. Downloaded from https://academic.oup.com/ijnp/article/17/Supplement_1/1/900273 by Faculty of Life Sciences Library user on 28 August 2020 I shall discuss the development of the endocannabinoid system – from the PL-01. The Arvid Carlsson Lecture: The ups and isolation and structure elucidation of delta-9-tetrahydrocannabinol in downs of amphetamines: A diversity of 1964, through the identification of the CB1 and CB2 receptors and the actions on cellular signaling pathways specific agonists anandamide and 2-AG, to the involvement of endocanna- binoids and structurally related endogenous molecules in a long list of bio- logical processes. Recent progress in several areas will be discussed: PL-01-001 The ups and downs of amphetamines: A diversity of A. Endocannabinoids as endogenous neuroprotective agents, particularly actions on cellular signaling pathways in traumatic injury; B. The CB2 cannabinoid receptors as part of a general S. G. Amara. National Institute of Mental Health, Bethesda, MD, USA protective system; C. Acyl fatty acids as novel endocannabinoid-like com- pounds; D. Cannabidiol as a novel therapeutic entity. Neurotransmitter transporters present at the plasma membrane contribute Policy of full disclosure: 1. I have no significant financial interest or to the clearance and recycling of neurotransmitters and have a profound other affiliation with a funding organization or with a commercial sup- impact on the extent of receptor activation during neuronal signaling. porter of the session and/or provider of commercial services. 2. I had a These carriers also are the primary targets for psychostimulant drugs of grant from NIH (ended 30 Nov 2013). abuse, antidepressant medications, and drugs such as methylphenidate and amphetamines, which are used to treat attention deficit disorders. This lecture will highlight several of the major signaling pathways that regulate dopamine transporter function and will also consider recent PL-04. Brain science using iPS cell technology work showing that amphetamine-like drugs can directly activate intra- non-human primates cellular signaling pathways in dopamine neurons to trigger changes in membrane protein trafficking and other cellular activities. Although sev- Brain science using iPS cell technology non-human eral steps in the process remain undefined, the intracellular actions of PL-04-001 primates amphetamine modulate both dopaminergic and glutamatergic signaling and contribute to the acute behavioral effects of the drug. These actions H. Okano. Keio University, Tokyo, Japan of amphetamine within dopamine neurons have implications for mechan- What makes the investigation of human psychiatric/psychiatric disorders isms of neuroplasticity and neurotoxicity associated with psychostimulant fi use and suggest novel drug targets for modulating the actions of so dif cult? This could be attributed to the following reasons 1) Diseases model mice do not always recapitulate the pathophysiology of human dis- amphetamines. fi Policy of full disclosure: None. eases, 2) It is extremely dif cult to investigate what is taking place in vivo at the onset of the disease due to the low accessibility to the pathological foci in the brain, and 3) The responsible neuronal circuits for the pheno- fi fi – type are not identi ed. In order to overcome these dif culties, we took ad- PL-02. Nobel Lecture Structural insights into vantage of iPS cell technologies and transgenic non-human primates for G protein coupled receptor signaling modeling human psychiatric/psychiatric disorders. So far, we have estab- lished iPS cells from the patients of more than 25 human psychiatric/psy- PL-02-001 Nobel Lecture – Structural insights into G protein chiatric disorders and characterized their pathophysiology. For example, coupled receptor signaling in collaboration with the group of RIKEN BSI and University of Tokyo, we established iPS cells from the schizophrenia patients containing B. Kobilka. Department of Molecular and Cellular Physiology, Stanford 22q11 deletions (Bundo et al., Neuron, 2014). Interestingly, we found University, USA that the copy number of a retrotransposon, long interspersed nuclear G protein coupled receptors (GPCRs) conduct the majority of transmem- element-1 (L1), was increased in neurons induced from iPS cells from brane responses to hormones and neurotransmitters, and mediate the schizophrenia patients containing 22q11 deletions, indicating that hyper- senses of sight, smell and taste. The β2 adrenergic receptor (β2AR) and active retrotransposition of L1 in neurons triggered by genetic risk factors the M2 muscarinic receptors are prototypical Family A GPCRs that med- may contribute to the susceptibility and pathophysiology of schizo- iates physiologic responses to autonomic nervous system activity. We phrenia. Furthermore, for faithfully modeling the human human psychi- have obtained three-dimensional structures of the β2AR and the M2 mus- atric/psychiatric disorders in vivo, we developed transgenic non-human carinic receptor in inactive and active conformations, as well as a structure primates (common marmosets) with germline transmission (Sasaki of the β2AR in complex with the G protein Gs. We have also used fluor- et al., Nature, 2009). In the present talk, we also wish to mention our re- escence, EPR and NMR spectroscopy to study the dynamic properties of cent data of generation of common marmoset transgenic models of neuro- the β2AR, and to map ligand-specific conformational changes. I will dis- degenrerative diseases, including Parkinson disease, Alzheimer disease cuss what we these studies have taught us about allosteric regulation of and ALS. I will also mention about our recent trials on the development GPCR structure by G proteins and ligands. of knock-in and knock-out technologies of common marmoset using gen- Policy of full disclosure: There is no financial conflict of interest. ome editing technologies for the generation of transgenic marmoset model of autism and psychiatric disorders. Policy of full disclosure: H. Okano is the scientific consultant of San Bio, Inc; Eisai Co Ltd; and Daiichi Sankyo Co Ltd. Tuesday 24 June 2014 PL-03. The endocannabinoid system – a fifty years trip PL-03-001 The endocannabinoid system – a fifty years trip R. Mechoulam. Institute for Drug Research, Hebrew University, Jerusalem, Israel The endocannabinoid system was discovered and we learned about its in- volvement in biological processes only over the last two decades – many years after the better known adrenergic, serotonergic or cholinergic systems. However it has already been suggested that ” modulating endocannabinoid 2 Plenary Lectures, Thursday 26 June 2014 Wednesday 25 June 2014 mechanisms as well as the native structure and complexity of the nervous system (6). PL-05. Preventive strategies in emerging mental disorders in young people: Clinical staging References and translational research 1. Deisseroth K (2010) Optogenetics: controlling the brain with light. Scientific American 303(5): 48–55. PL-05-001 Preventive strategies in emerging mental disorders in 2. Deisseroth K (2011) Optogenetics. Nature Methods 8: 26–9. young people: Clinical staging and translational 3. Kim SY, Adhikari A, Lee SY, Marshel JH, Kim CK, Mallory CS, Lo M, research Pak S, Mattis J, Lim BK, Malenka RC, Warden MR, Neve R, Tye KM & Downloaded from https://academic.oup.com/ijnp/article/17/Supplement_1/1/900273 by Faculty of Life Sciences Library user on 28 August 2020 Deisseroth K (2013). Assembling behavioral states: divergent neural P. McGorry. Orygen Youth Health Research Centre, University of Melbourne, pathways recruit separable anxiety features. Nature 496: 219–23. Melbourne, Australia 4. Warden M, Selimbeyoglu A, Mirzabekov J, Lo M, Thompson K, A key goal in psychiatry is to build new diagnostic, therapeutic and Kim S, Adhikari A, Tye K, Frank L & Deisseroth K (2012). A pre- translational tools and capacity to reduce the impact of emerging mental frontal cortex-brainstem projection controlling response to behavioral disorders in young people on survival, distress, quality of life and pro- challenge. Nature 492: 428–32. ductivity. Young people bear the major burden of onset for mental dis- 5. Chung K, Wallace J, Kim S, Kalyanasundaram S, Andalman A, orders with 75% of such illnesses appearing before age 25 years. This can Davidson T, Mirzabekov J, Zalocusky K, Mattis J, Denisin A, Pak S, only be done within a novel non-stigmatising interface between young Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V & people