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SUPPLEMENT TO JOURNAL OF PSYCHOPHARMACOLOGY VOL 26, SUPPLEMENT TO ISSUE 8, AUGUST 2012 These papers were presented at the Summer Meeting of the BRITISH ASSOCIATION FOR PSYCHOPHARMACOLOGY 22 – 25 July, Harrogate, 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. BAP OFFICE 36 Cambridge Place Hills Road Cambridge CB2 1NS bap.org.uk Aii CONTENTS Abstract Book 2012 Abstracts begin on page: SYMPOSIUM 1 A1 Drugs as tools in neuropsychiatry: Ketamine (S01-S04) SYMPOSIUM 2 A2 New tricks for old drugs: Opiates, addiction and beyond (S05-S08) SYMPOSIUM 3 A3 Advances in understanding brain corticosteroid responses to stress: relevance to depression (S09-S12) SYMPOSIUM 4 A5 Cognitive impairment in depression: A target for treatment? (S13-S16) SYMPOSIUM 5 A6 New treatment strategies for targeting drug addictions – A translational perspective (S17-S20) SYMPOSIUM 6 A7 Functional imaging markers for monitoring treatment: Mechanisms and efficacy (S21-S24) SYMPOSIUM 7 A9 Schizophrenia Treatment: What’s wrong with it and what might work better (S25-S28) SYMPOSIUM 8 A10 Epigenetics and psychiatry - current understanding and therapeutic potential (S29-S32) SYMPOSIUM 9 A11 Rethinking the compulsive aspects of addiction: From bench to bedside (S33-S36) POSTERS Anxiety 1 (MA01-MA07) A13 Affective Disorders 1 (MB01-MB20) A16 Brain Imaging (MC01-MC12) A24 Cognition 1 (MD01-MD09) A29 Educational Psychopharmacology (ME01-ME05) A33 CONTENTS Aiii Abstract Book 2012 (continued) Abstracts begin on page: Schizophrenia 1 (MF01-MF13) A35 Substances of Abuse 1 (MG01-MG09) A40 Anxiety 2 (TA01-TA05) A44 Affective Disorders 2 (TB01-TB21) A46 Sleep (TC01-TC05) A54 Cognition 2 (TD01-TD10) A56 Neuropharmacology (TE01-TE07) A60 Schizophrenia 2 (TF01-TF11) A63 Feeding and Eating (TG01-TG03) A67 Substances of Abuse 2 (TH01-TH15) A68 Psychomotor Stimulants (TI01-TI03) A73 POSTDOCTORAL SYMPOSIUM A74 Neurodevelopmental models of psychiatric disease: back to the future (PD01-PD04) SHORT ORAL PRESENTATIONS Short Orals 1: New ways to model anxiety See abstracts MA01, MA05, MA04, MA07 Short Orals 2: Cognitive enhancement: From aspiration to realisation See abstracts TD06, SO01 (page A75), TD08, TF06 Short Orals 3: Cannabinoids: Toxic effects and treatment applications See abstracts TF04, MG03, MG05, MG04 GUEST LECTURE (GL1) A75 BAP PSYCHOPHARMACOLOGY AWARD WINNERS (PW1-PW3) A76 ABSTRACTS A1 S01 THE TRANSLATIONAL NEUROPHARMACOLOGY OF KETAMINE Deakin JFW, Neuroscience and Psychiatry Dept, Univ of Manchester, G907 Stopford Building Oxford Rd Manchester M13 9PT, [email protected] The acute psychotomimetic effects of drugs that block the ion-channel associated with the NMDA glutamate receptor such as phencyclidine and ketamine have been the focus of much research interest for several decades. More recently, therapeutic effects in depression have been reported that emerge after some hours after a single dose of ketamine. This presentation focuses on the use of ketamine to understand the mode of action of two novel drugs: minocycline for negative symptoms of schizophrenia (Chaudhry et al, J Psychopharmacol 2012 (in press)); and AZ 6765, a NMDA channel blocker for depression. The translational tools were electrophysiology and blood oxygenation level dependent (BOLD) MRI imaging of drug effects using pharmaco-MRI (phMRI). In electrophysiological studies in the rat, ketamine, like other NMDA channel-blockers, caused a marked activation of hippocampal and frontal cortical neuronal fi ring rate and desynchronisation of the predominant delta rhythm associated with α-chloralose anaesthesia. Minocycline pre-treatment completely prevented the desychronisation induced by ketamine without affecting the increased fi ring rate. Translational studies with ketamine point to a novel glutamatergic action of minocycline in facilitating integrative function in cortex. Depression has been associated with over-activity of the subgenual cingulate cortex (SCG) which normalises with recovery. An acute iv bolus infusion of ketamine was previously reported to decrease BOLD signal in SGC in healthy volunteers (Deakin JFW et al, Arch General Psychiat 2008; 65:154-64). We investigated whether AZD6765 and ketamine shared this effect in 60 depressed participants when administered as a slow intravenous infusion and whether SCG effects were associated with clinical outcome 24 and 7 days later. The study was carried out in Manchester and Oxford, UK. Against our prediction, no decreases following drug were seen in any region compared to saline. Instead both drugs gradually increased SGC BOLD signal during the infusion. SCG was the only area in which phMRI responses to drug correlated with improvement in Montgomery- Asberg mood ratings scale 24hrs and 7 days later. Interviewer-rated psychotic and dissociative symptoms were minimal and not statistically signifi cant after AZ6765 but statistically signifi cant after ketamine. Improvement in mood did not differ between active and placebo treatments. The results suggest that AZ6765 and ketamine have antidepressant - like effects on emotion processing in the brain, that these effects may be initiated by actions on the SGC, and that diminished NMDA glutamate neurotransmission is the immediate mechanism. Funding: AstraZeneca, Medical Research Council UK, Stanley Medical Research Institute S02 KETAMINE IN HEALTHY VOLUNTEERS AS A MODEL OF SCHIZOPHRENIA Fletcher PC, Psychiatry, Univ of Cambridge, Herchel Smith Bldg Addenbrooke’s Hospital, West Forvie Site Robinson Way, Cambridge, CB2 0SZ, [email protected] Introduction: Acute administration of the competitive NMDA antagonist, ketamine, to healthy people produces a complex array of perceptual, cognitive and motor changes that are strikingly redolent of early psychosis. The purpose of a drug model, however, should go beyond replicating key characteristics of a syndrome and should aim, in addition, to establish both construct and predictive validity. That is, it should be possible to show that the drug reproduces the key symptoms by acting on brain circuitry known to be disturbed in association with the syndrome and it should moreover be possible to show that the symptoms that it produces are related to, and predicted by, its underlying effects on brain and cognition. The work reported here explored these possibilities in the context of the ketamine model of psychotic symptoms and is based on the suggestion that these symptoms occur as a consequence of a derangement in prediction error-dependent learning. It is a model that appeals more broadly to the predictive coding model of psychosis. Methods: We used serial studies on overlapping participant groups. The aim was initially to defi ne neural markers for a specifi c prediction error-dependent learning process. Subsequently, these subjects participated in a placebo-controlled study of ketamine’s effects on perception, experience and cognitive performance. The central aim was to determine whether individual variability in neural responses to prediction error were predictive of individual vulnerability to the effects of subsequent ketamine administration. This would provide evidence of a link between a specifi c neural response, a cognitive process and a neurochemical perturbation in subjective experiences. Such a link would be valuable in assessing the validity of the cognitive model of psychosis underlying the experiment. Results: Frontal and striatal activity measured during the initial phase of testing covaried strongly with prediction error-dependent learning. Variations in these responses predicted the effects of ketamine on cognitive performance in learning tasks as well as the tendency of the drug to produce mild symptoms of psychosis. Conclusions: Administration of ketamine produces a constellation of perceptual and cognitive effects, as well as psychosis-like symptoms. As well as being strikingly redolent of early psychotic illness, these are related to alterations in prediction error-dependent learning processes. People in whom neural responses to such processes are greater appear to show increased vulnerability to the drug’s effects. This intimate relationship between process-specifi c neural responding and ketamine-related disturbance may offer important insights to the neurobiology of how psychotic symptoms emerge. S03 KETAMINE AND THE POTENTIAL ROLE FOR RAPID ACTING ANTIDEPRESSANTS Krystal JH, Psychiatry Yale University School of Medicine, 300 George St., Suite 901, New Haven, CT 06511 USA [email protected] There is a tremendous need for antidepressant treatments that work more rapidly and more effectively than available treatments. Our current antidepressant treatments (monoamine reuptake or metabolism modulators, lithium, ECT) have been in place for over 50 years. This presentation will review the path that let to the identifi cation of ketamine as the fi rst rapid onset antidepressant treatment. Ketamine is a short-acting NMDA glutamate receptor antagonist. A series of studies now demonstrate that a single intravenous dose of ketamine will produce reductions in depression severity within several hours and remission of depression in many patients within 24 hours. The antidepressant effects of a single dose of ketamine appear to last generally, from several days to several weeks. In light of evidence that suicidal ideation improves with
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