BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Schizophrenia and psychotic disorders - Peter Jones (Dept of Psych iatry) DTSTART:20100308T160000Z DTEND:20100308T173000Z UID:TALK21959@talks.cam.ac.uk CONTACT:Mandy Carter DESCRIPTION:A decade for psychiatric disorders\n\nThere are many ways in w hich the understanding and treatment of conditions such as schizophrenia a re ripe for a revolution. A media circus surrounded President Bill Clinton 's visit to a New York medical centre in 2004 for a quadruple heart bypass .\n\nYet barely a whisper was heard about other high-profile individuals'v isits there for the treatment of psychiatric disorders. In Britain\, the p ublic donates £500 million (US$800 million) each year to charities for ca ncer research. For mental-health research\, the figure is a few million\, and most of that is for work on neurodegenerative diseases such as Alzheim er's\, rather than for earlieronset conditions that can undermine people's entire lives\, such as depressive disorders. It is time for such disparit ies to be addressed in a more coherent and aggressive way than in the past . The stigma of psychiatric disorders is misplaced\, their burdens on soci ety are significantly greater than more publicized diseases in developed a nd developing nations alike\, and biomedical science is poised to make sig nificant strides. The timescales are daunting and the challenges great — human neurons are less accessible than tumour cells\, separating genetic and environmental influences is tough\, and the diagnosis of the condition s is highly problematic. There is much to be done\, and a decade is the ti mescale over which enhanced commitment is required. The problem of stigma persists. In some countries\, progress in this regard has been made with d epression: a few high-profile and brave sufferers in some Western countrie s have stood up and identified themselves. By contrast\, schizophrenia\, w hen covered by the media at all\, is mostly associated with murders carrie d out by a tiny minority of sufferers who have an acute form of the condit ion.\n\nResearch challenges\n\nSchizophrenia — a combination of delusion s\, reduced motivation and diminished cognitive functions — exemplifies many of the research challenges posed by psychiatric disorders as a whole. The extreme behaviours covered by the media are far from typical. Populat ion studies indicate that the lifetime prevalence of all psychotic disorde rs (whose sufferers experience some sort of misperception of reality) is a s much as 3%. Schizophrenia is controllable by medication and cognitive th erapy\, with a significant chance (a few tens of per cent) of beneficial p ositive outcomes. Frustratingly\, the effectiveness of medications has sta lled. Nobody understands the links between the symptoms of schizophrenia a nd the crude physiological pathologies that have so far been documented: a decrease in white brain matter\, for example\, and altered function of th e neurotransmitter dopamine. The medications\, which are often aimed at th e dopamine systems associated with delusions\, have advanced over the deca des not in their efficacy but in a reduction of their debilitating side ef fects. Both diagnosis and drugs primarily address a late stage in the deve lopment of schizophrenia — the presentation of delusions. The earlier st ages are much less well defined and are ambiguous in that\, as currently c haracterized\, they could lead to a number of alternative conditions. Here \, above all\, is where progress is needed in the form of reliable biomark ers to identify those at risk and to allow biomedical or cognitive interve ntions to prevent or mitigate the development of the disorders. Early inte rvention would lead to better outcomes. A deeper understanding of the unde rlying biology is essential to improve diagnoses and therapies. New techni ques — genome-wide association studies\, imaging and the optical manipul ation of neural circuits — are ushering in an era in which the neural ci rcuitry underlying cognitive dysfunctions\, for example\, will be delineat ed. Tantalizingly\, work in genetics is indicating how non-specific some g enes are for schizophrenia\, having associations in common with bipolar di sorder and with autism. This suggests that the earlier stages of psychiatr ic disorders are multi valent\, reinforcing the hope that early detection\ , coupled with a clearer understanding of the environmental factors\, may allow prevention.\n\nEnvironmental influence\n\nToo little fundamental res earch is devoted to environmental factors. About 80% of the pattern of sch izophrenia in populations seems to be determined by genetics\, but part of that genetic influence lies in susceptibility to environmental influences . The remaining 20% of direct environmental influence is also ripe for mor e extensive investigation — epidemiological studies point to social stre ss (associated\, for example\, with migration or urbanization) as a signif icant influence\, albeit in a minority of schizophrenia sufferers. As stat ed in a recent review of schizophrenia\, a "worldwide challenge is to brin g together the various disciplines that are needed to examine models of di sease causation based on various aspects of gene–environment interplay" (J. van Os and S. Kapur Lancet 374\, 635–645\; 2009). Of course it won't be just the basic biology of molecules and their circuits that will be es sential in understanding the mechanisms of schizophrenia. There is a highe r level of explanation required to understand\, for example\, delusions an d their persistence. Whether for schizophrenia\, depression\, autism or an y other psychiatric disorders\, it is clear\, as Tom Insel\, head of the U S National Institute of Mental Health has emphasized (T. R. Insel J. Clin. Invest. 119\, 700–705\; 2009)\, that understanding of these conditions is entering a scientific phase more penetratingly insightful than has hith erto been possible. But Insel also highlights the disruptive impact of the science on the practices of clinical psychiatrists — as biological insi ghts develop\, the crudity of current psychiatric diagnoses will become al l too clear. Yet the exposure of many psychiatrists to contemporary biolog y is shallow at best. That\, too\, will need to change over the next decad e. Nat Rev Neurosci. 2009 Jan\;10(1):48-58. Epub 2008 Dec 3.\nPerceiving i s believing: a Bayesian approach to explaining the positive symptoms of sc hizophrenia.\n\nFletcher PC\, Frith CD.\n\nUniversity of Cambridge\, Depar tment of Psychiatry\, Addenbrooke's Hospital\, Hills Road\, Cambridge\, CB 2 2QQ\, UK.\n\nAdvances in cognitive neuroscience offer us new ways to und erstand the symptoms of mental illness by uniting basic neurochemical and neurophysiological observations with the conscious experiences that charac terize these symptoms. Cognitive theories about the positive symptoms of s chizophrenia--hallucinations and delusions--have tended to treat perceptio n and belief formation as distinct processes. However\, recent advances in computational neuroscience have led us to consider the unusual perceptual experiences of patients and their sometimes bizarre beliefs as part of th e same core abnormality--a disturbance in error-dependent updating of infe rences and beliefs about the world. We suggest that it is possible to unde rstand these symptoms in terms of a disturbed hierarchical Bayesian framew ork\, without recourse to separate considerations of experience and belief .\n\nBr J Psychiatry. 2009 Nov\;195(5):382-90.\nHarmonisation of ICD-11 an d DSM-V: opportunities and challenges.\n\nFirst MB.\n\nNew York State Psyc hiatric Institute\, Columbia University Department of Psychiatry\, 1051 Ri verside Drive - Unit 60\, New York\, NY 10032\, USA. mbf2@columbia.edu\n\n Comment in:\n\n * Br J Psychiatry. 2009 Nov\;195(5):379-81.\n\nBACKGROU ND: Differences in the ICD-10 and DSM-IV definitions for the same disorder impede international communication and research efforts. The forthcoming parallel development of DSM-V and ICD-11 offers an opportunity to harmonis e the two classifications. AIMS: This paper aims to facilitate the harmoni sation process by identifying diagnostic differences between the two syste ms. METHOD: DSM-IV-TR criteria sets and the ICD-10 Diagnostic Criteria for Research were compared and categorised into those with identical definiti ons\, those with conceptually based differences and those in which differe nces are not conceptually based and appear to be unintentional. RESULTS: O f the 176 criteria sets in both systems\, only one\, transient tic disorde r\, is identical. Twenty-one per cent had conceptually based differences a nd 78% had non-conceptually based differences. CONCLUSIONS: Harmonisation of criteria sets\, especially those with non-conceptually based difference s\, should be prioritised in the DSM-V and ICD-11 development process. Pri or experience with the DSM-IV and ICD-10 harmonisation effort suggests tha t for the process to be successful steps should be taken as early as possi ble.\n\nCannabis use and risk of psychotic or affective mental health outc omes: a systematic review.\n\nMoore TH\, Zammit S\, Lingford-Hughes A\, Ba rnes TR\, Jones PB\, Burke M\, Lewis G.\n\nLancet. 2007 Jul 28\;370(9584): 319-28. Review.PMID: 17662880 [PubMed - indexed for MEDLINE]Related articl es\n\nHum Genet. 2009 Jul\;126(1):3-12. Epub 2009 Jun 12.\nGenetics of psy chosis\; insights from views across the genome.\n\nO'Donovan MC\, Craddock NJ\, Owen MJ.\n\nDepartment of Psychological Medicine and Neurology\, MRC Centre for Neuropsychiatric Genetics and Genomics\, School of Medicine\, Heath Park\, Cardiff CF23 6BQ\, UK. odonovanmc@cf.ac.uk\n\nThe major psych otic illnesses\, schizophrenia and bipolar disorder (BD)\, are among the m ost heritable common disorders\, but finding specific susceptibility genes for them has not been straightforward. The reasons are widely assumed to include lack of valid phenotypic definition\, absence of good theories of pathophysiology for candidate gene studies\, and the involvement of many g enes\, each making small contributions to population risk. Within the last year or so\, a number of genome wide association (GWAS) of schizophrenia and BD have been published. These have produced stronger evidence for asso ciation to specific risk loci than have earlier studies\, specifically for the zinc finger binding protein 804A (ZNF804A) locus in schizophrenia and for the calcium channel\, voltage-dependent\, L type\, alpha 1C subunit ( CACNA1C) and ankyrin 3\, node of Ranvier (ANK3) loci in bipolar disorder. The ZNF804A and CACNA1C loci appear to influence risk for both disorders\, a finding that supports the hypothesis that schizophrenia and BD are not aetiologically distinct. In the case of schizophrenia\, a number of rare c opy number variants have also been detected that have fairly large effect sizes on disease risk\, and that additionally influence risk of autism\, m ental retardation\, and other neurodevelopmental disorders. The existing f indings point to some likely pathophysiological mechanisms but also challe nge current concepts of disease classification. They also provide grounds for optimism that larger studies will reveal more about the origins of the se disorders\, although currently\, very little of the genetic risk of eit her disorder is explained.\n\nSchizophrenia genes\, gene expression\, and neuropathology: on the matter of their convergence.\n\nHarrison PJ\, Weinb erger DR.\n\nMol Psychiatry. 2005 Jan\;10(1):40-68\; image 5. Review. Erra tum in: Mol Psychiatry. 2005 Apr\;10(4):420. Mol Psychiatry. 2005 Aug\;10( 8):804. PMID: 15263907 [PubMed - indexed for MEDLINE]Related articl es\n\n Kirkbride JB & Jones PB\, 2008\, The Mental Ill-Health of People Who Migra te and Their Descendants: Risk Factors\, Associated Disability and Wider C onsequences. Mental Capital and Wellbeing Foresight State of Science Revie w SR-B13. Accessible from\n\nhttp://www.foresight.gov.uk/OurWork/ActivePro jects/Mental%20Capital/ProjectOutputs.asp LOCATION:Department of Experimental Psychology Seminar Room END:VEVENT END:VCALENDAR