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JOURNAL OF PSYCHOPHARMACOLOGY SUPPLEMENT TO VOLUME 28, ISSUE 8, AUGUST 2014 These papers were presented at the Summer Meeting of the BRITISH ASSOCIATION FOR PSYCHOPHARMACOLOGY 20 – 23 July, Cambridge, UK Indemnity The scientific material presented at this meeting reflects the opinions of the contributing authors and speakers. The British Association for Psychopharmacology accepts no responsibility for the contents of the verbal or any published proceedings of this meeting. All contributors completed a Declaration of Interests form when submitting their abstract BAP Office 36 Cambridge Place Hills Road Cambridge CB2 1NS www.bap.org.uk Aii CONTENTS Abstract Book 2014 Abstracts begin on page: SYMPOSIUM 1 Psycho-immunology (S01-S04) A1 SYMPOSIUM 2 Predictors of clinical response in depression (S05-S08) A2 SYMPOSIUM 3 ADHD and obesity: Overlapping neurobiology and development of pharmacological treatments (S09-S12) A3 SYMPOSIUM 4 Cannabinoids in psychiatry: Current understanding and future treatments (S13-S16) A4 SYMPOSIUM 5 Chickens and Eggs: Separating cause and effect in drug addiction (S17-S20) A6 SYMPOSIUM 6 Genetic pathways in psychosis: the road to new treatments? (S21-S24) A7 SYMPOSIUM 7 The adolescent brain – A key stage in the development of psychiatric disorders? (S25-S28) A8 SYMPOSIUM 8 Tobacco addiction in schizophrenia: a translational investigation (S29-S32) A9 SYMPOSIUM 9 Dopamine, impulse control disorders and Parkinson’s disease (S33-S36) A11 POSTERS Cognition (Animals) (MA01-MA14) A12 Drug Dependence (Human) (MB01-MB28) A19 Affective Disorders 1 (MC01-MC28) A32 Schizophrenia/Psychosis (Human) (MD01-MD27) A46 Anxiety (Nonclinical) (ME01-ME14) A59 Neurodegeneration (MF01-MF08) A66 Sleep/Pain (MG01-MG04) A70 CONTENTS Aiii Eating Disorders (MH01-MH07) A72 Cognition (Humans) (TA01-TA21) A75 Drug Dependence (Animals) (TB01-TB12) A84 Affective Disorders 2 (TC01-TC39) A90 Schizophrenia/Psychosis (Animal) (TD01-TD15) A109 Anxiety (Patients) (TE01-TE09) A116 ADHD/ASD (TF01-TF10) A120 POSTDOCTORAL SYMPOSIUM Understanding vulnerability for treatment improvement (PD1-PD4) A125 SHORT ORAL PRESENTATIONS Short Orals 1: Inflammation Insights See abstracts TC33, TD13, TC36, TE06 Short Orals 2: Understanding Cognition and Emotion See abstracts TA10, TA11, ME03, TA03 Short Orals 3: Developing Depression See abstracts TC15, MC03, MC26, MC28 PRIZE WINNER ABSTRACTS (PW1-PW6) A127 ABSTRACTS A1 S01 IT IS ALL IN THE BODY: MOLECULAR MECHANISMS BY WHICH PERIPHERAL IMMUNE ACTIVATION INDUCES DEPRESSION Pariante C, Dept of Psychological Medicine, Inst of Psychiatry, Room 2-055, The James Black Centre, 125 Coldharbour Lane, London SE5 9NU, [email protected] The notion that increased peripheral immune activation may induce depression has developed over the last twenty years, largely as a consequence of two major breakthroughs occurring in the 90s: the experimental evidence using animal models that immune activation leads to behavioural changes resembling depression (sickness behaviour), and the clinical evidence that patients exposed to cytokine therapies for cancers or chronic viral hepatitis develop clinically-significant depression. This initial evidence has been then corroborated by cross-sectional and longitudinal studies that have shown that some depressed patients have increased markers of inflammation, and that increased inflammation in otherwise healthy individuals is a risk factor for the future onset of depression. This talk will offer an historical overview of the evidence supporting the notion that increased peripheral inflammation is on the causal pathway to depression, and will present more recent findings on the molecular mechanisms that are involved in this causal pathway. In particular, this talk will discuss our recent findings, from both experimental and clinical research, showing that increased peripheral inflammation directly affects brain function by reducing hippocampal size, by decreasing neurogenesis and by stimulating the production of neurotoxic and depressogenic metabolites; and that increased peripheral markers of inflammation, both as serum biomarker and as mRNA expression, identifies depressed patients that are less likely to respond to conventional antidepressants, possibly because of a more “developmental” form of depression originating in early life trauma. Finally, this talk will also discuss potential molecular mechanisms by which some antidepressants, including omega-3 fatty acids, have an anti-inflammatory action that could be relevant for their antidepressants effects. In conclusion, twenty years of research on depression and immune system are finally bringing “personalised medicine” right into the core of psychiatry research and patients’ care. S02 COMPLEMENT AND INNATE IMMUNITY IN ALZHEIMER’S DISEASE - BIOMARKERS, AETIOLOGY AND THERAPEUTIC OPPORTUNITY Lovestone S, Dept of Translational Neuroscience, Univ of Oxford, Dept of Psychiatry, Warneford Hospital Oxford OX3 7JX simon.lovestone@ psych.ox.ac.uk It has long been recognised from post-mortem studies that inflammation is a component of the pathological process ofAlzheimer’s disease and from epidemiological observations that anti-inflammatory drugs reduce risk of dementia. However, the precise inflammatory component has remained elusive, the postulated roles of inflammation as an aetiopathological agent versus a role as an inconsequential bystander has been controversial and trials of anti-inflammatory drugs have proved unsuccessful. However, this is now changing and increasingly research suggests both that it is the complement system that mediates disease and that interventions targeting complement might be a productive therapeutic strategy. Our own research seeking biomarkers for AD strongly implicates the immune system in the pathological process of AD. Using proteomics we and others have shown elements of the complement system including CFH, C3, clusterin and other molecules are consistently altered and are part of a panel we have recently identified that predicts conversion from MCI with a high degree of accuracy. In addition, other elements of the innate immune system including cytokines are unambiguously altered in AD. Evidence that this reflects a primary aetipothological process comes from genome wide studies which identify complement genes such as CLU and CR1 as important susceptibility factors and where pathway analyses consistently point to the complement system as a mediator of disease. Building on these findings we have conducted a preliminary study using therapeutics designed to target the complement system and early evidence suggests benefits in reducing some aspects ofAD pathology in in vivo models. S03 CHRONIC DISEASE, NEUROINFLAMMATION AND ITS IMPACT ON THE CNS Perry VH, Centre for Biological Sciences, Univ of Southampton, Mail Point 840, LD80B South Lab and Path Block, Southampton General Hospital SO16 6YD [email protected] During progression of a number of neurodegenerative disease such as Alzheimer’s disease, Parkinson’s disease, and prion diseases there is an innate immune response in the brain. This innate immune response is characterised by an increase in the density of the microglia, and their ‘activation’ as judged by alterations in their morphology and the upregulation or de novo synthesis of macrophage antigens. Systemic inflammation can have a profound impact on the phenotype of these microglia that appear to be ‘primed’ by the ongoing neurodegeneration. Proliferation and priming of the microglia is driven at least in part by CSF1, IL-34 via the CSFR1. Systemic inflammation in diverse animal models of chronic neurodegenerative disease leads to exaggerated cytokine synthesis in the brain relative to naive animals, exaggerated sickness behaviour and acceleration of components of disease progression. Understanding how systemic co-morbidities contribute to progression of chronic neurodegenerative disease offers a route to slowing disease progression and improving the quality of life of those with neurodegenerative disease. A2 ABSTRACTS S04 IMMUNOPSYCHIATRY - CAN WE USE IMMUNOLOGICAL MECHANISMS TO DEVELOP NEW DRUGS FOR PSYCHIATRIC DISORDERS? Bullmore ET, ImmunoPsychiatry, GlaxoSmithKline, Clinical Unit, Cambridge Addenbrookes Centre for Clinical Investigations, Cambridge Biomedical Campus, CB20GG [email protected] The last 10 years have been a challenging period for development of new drugs for psychiatric disorders, with many companies reducing their levels of investment, despite clear evidence of high levels of unmet need. In this talk, I will briefly rehearse the reasons for the riskiness of drug development in psychiatry and argue that refocusing on immune targets may offer a new way forward that could be more productive than traditional approaches focused on neuronal targets. Specifically, I will address 3 key questions about immunopsychiatry. (1) What is the reason to believe? This will highlight some of the key findings to emerge from the literature that suggest immunological mechanisms could be important in pathogenesis and therapeutics in psychiatry. (2) How will it be different this time? This will point to the potential impact of mechanistically specific and peripherally accessible biomarkers from immunological assays on blood or CSF, and the economic advantages in repurposing anti-inflammatory drugs already in development or marketed for other idnciations. (3) What will success look like? This will speculate on the potential indications or diagnostic subgroups that might prove to be amenable to immunotherapeutics