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:20110314T160000Z DTEND:20110314T173000Z UID:TALK28731@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 bypa ss.\n\nYet barely a whisper was heard about other high-profile individuals ’visits there for the treatment of psychiatric disorders. In Britain\, t he public donates £500 million (US$800 million) each year to charities fo r cancer research. For mental-health research\, the figure is a few millio n\, and most of that is for work on neurodegenerative diseases such as Alz heimer’s\, rather than for earlieronset conditions that can undermine pe ople’s entire lives\, such as depressive disorders. It is time for such disparities to be addressed in a more coherent and aggressive way than in the past. The stigma of psychiatric disorders is misplaced\, their burdens on society are significantly greater than more publicized diseases in dev eloped and developing nations alike\, and biomedical science is poised to make significant strides. The timescales are daunting and the challenges g reat — human neurons are less accessible than tumour cells\, separating genetic and environmental influences is tough\, and the diagnosis of the c onditions is highly problematic. There is much to be done\, and a decade i s the timescale over which enhanced commitment is required. The problem of stigma persists. In some countries\, progress in this regard has been mad e with depression: a few high-profile and brave sufferers in some Western countries have stood up and identified themselves. By contrast\, schizophr enia\, when covered by the media at all\, is mostly associated with murder s carried out by a tiny minority of sufferers who have an acute form of th e condition.\n\nResearch challenges\n\nSchizophrenia — a combination of delusions\, reduced motivation and diminished cognitive functions — exem plifies many of the research challenges posed by psychiatric disorders as a whole. The extreme behaviours covered by the media are far from typical. Population studies indicate that the lifetime prevalence of all psychotic disorders (whose sufferers experience some sort of misperception of reali ty) is as much as 3%. Schizophrenia is controllable by medication and cogn itive therapy\, with a significant chance (a few tens of per cent) of bene ficial positive outcomes. Frustratingly\, the effectiveness of medications has stalled. Nobody understands the links between the symptoms of schizop hrenia and the crude physiological pathologies that have so far been docum ented: a decrease in white brain matter\, for example\, and altered functi on of the neurotransmitter dopamine. The medications\, which are often aim ed at the dopamine systems associated with delusions\, have advanced over the decades not in their efficacy but in a reduction of their debilitating side effects. Both diagnosis and drugs primarily address a late stage in the development of schizophrenia — the presentation of delusions. The ea rlier stages are much less well defined and are ambiguous in that\, as cur rently characterized\, they could lead to a number of alternative conditio ns. Here\, above all\, is where progress is needed in the form of reliable biomarkers to identify those at risk and to allow biomedical or cognitive interventions to prevent or mitigate the development of the disorders. Ea rly intervention would lead to better outcomes. A deeper understanding of the underlying biology is essential to improve diagnoses and therapies. Ne w techniques — genome-wide association studies\, imaging and the optical manipulation of neural circuits — are ushering in an era in which the n eural circuitry underlying cognitive dysfunctions\, for example\, will be delineated. Tantalizingly\, work in genetics is indicating how non-specifi c some genes are for schizophrenia\, having associations in common with bi polar disorder and with autism. This suggests that the earlier stages of p sychiatric disorders are multi valent\, reinforcing the hope that early de tection\, coupled with a clearer understanding of the environmental factor s\, may allow prevention.\n\nEnvironmental influence\n\nToo little fundame ntal research is devoted to environmental factors. About 80% of the patter n of schizophrenia in populations seems to be determined by genetics\, but part of that genetic influence lies in susceptibility to environmental in fluences. The remaining 20% of direct environmental influence is also ripe for more extensive investigation — epidemiological studies point to soc ial stress (associated\, for example\, with migration or urbanization) as a significant influence\, albeit in a minority of schizophrenia sufferers. As stated in a recent review of schizophrenia\, a “worldwide challenge is to bring together the various disciplines that are needed to examine mo dels of disease causation based on various aspects of gene–environment i nterplay” (J. van Os and S. Kapur Lancet 374\, 635–645\; 2009). Of cou rse it won’t be just the basic biology of molecules and their circuits t hat will be essential in understanding the mechanisms of schizophrenia. Th ere is a higher level of explanation required to understand\, for example\ , delusions and their persistence. Whether for schizophrenia\, depression\ , autism or any other psychiatric disorders\, it is clear\, as Tom Insel\, head of the US National Institute of Mental Health has emphasized (T. R. Insel J. Clin. Invest. 119\, 700–705\; 2009)\, that understanding of the se conditions is entering a scientific phase more penetratingly insightful than has hitherto been possible. But Insel also highlights the disruptive impact of the science on the practices of clinical psychiatrists — as b iological insights develop\, the crudity of current psychiatric diagnoses will become all too clear. Yet the exposure of many psychiatrists to conte mporary biology is shallow at best. That\, too\, will need to change over the next decade. Nat Rev Neurosci. 2009 Jan\;10(1):48-58. Epub 2008 Dec 3. Perceiving is believing: a Bayesian approach to explaining the positive s ymptoms of schizophrenia.\n\nFletcher PC\, Frith CD.\n\nUniversity of Camb ridge\, Department of Psychiatry\, Addenbrooke’s Hospital\, Hills Road\, Cambridge\, CB2 2QQ \, UK.\n\nAdvances in cognitive neuroscience offer us new ways to understand the symptoms of mental illness by uniting basic ne urochemical and neurophysiological observations with the conscious experie nces that characterize these symptoms. Cognitive theories about the positi ve symptoms of schizophrenia—hallucinations and delusions—have tended to treat perception 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 bel iefs as part of the same core abnormality—a disturbance in error-depende nt updating of inferences and beliefs about the world. We suggest that it is possible to understand these symptoms in terms of a disturbed hierarchi cal Bayesian framework\, without recourse to separate considerations of ex perience and belief.\n\nBr J Psychiatry. 2009 Nov\;195(5):382-90. Harmonis ation of ICD -11 and DSM -V: opportunities and challenges.\n\nFirst MB.\n\ nNew York State Psychiatric Institute\, Columbia University Department of Psychiatry\, 1051 Riverside Drive – Unit 60\, New York\, NY 10032 \, USA . mbf2@columbia.edu\n\nComment in:\n\n * Br J Psychiatry. 2009 Nov\;195 (5):379-81.\n\nBACKGROUND : Differences in the ICD -10 and DSM -IV definit ions for the same disorder impede international communication and research efforts. The forthcoming parallel development of DSM -V and ICD -11 offer s an opportunity to harmonise the two classifications. AIMS : This paper a ims to facilitate the harmonisation process by identifying diagnostic diff erences between the two systems. METHOD : DSM-IV-TR criteria sets and the ICD -10 Diagnostic Criteria for Research were compared and categorised int o those with identical definitions\, those with conceptually based differe nces and those in which differences are not conceptually based and appear to be unintentional. RESULTS : Of the 176 criteria sets in both systems\, only one\, transient tic disorder\, is identical. Twenty-one per cent had conceptually based differences and 78% had non-conceptually based differen ces. CONCLUSIONS : Harmonisation of criteria sets\, especially those with non-conceptually based differences\, should be prioritised in the DSM -V a nd ICD -11 development process. Prior experience with the DSM -IV and ICD -10 harmonisation effort suggests that for the process to be successful st eps should be taken as early as possible.\n\nCannabis use and risk of psyc hotic or affective mental health outcomes: a systematic review.\n\nMoore T H\, Zammit S\, Lingford-Hughes A\, Barnes TR\, Jones PB\, Burke M\, Lewis G.\n\nLancet. 2007 Jul 28\;370(9584):319-28. Review.PMID: 17662880 [PubMed – indexed for MEDLINE ]Related articles\n\nHum Genet. 2009 Jul\;126(1): 3-12. Epub 2009 Jun 12. Genetics of psychosis\; insights from views across the genome.\n\nO’Donovan MC\, Craddock NJ\, Owen MJ.\n\nDepartment of P sychological Medicine and Neurology\, MRC Centre for Neuropsychiatric Gene tics and Genomics\, School of Medicine\, Heath Park\, Cardiff CF23 6BQ \, UK. odonovanmc@cf.ac.uk\n\nThe major psychotic illnesses\, schizophrenia a nd bipolar disorder (BD)\, are among the most heritable common disorders\, but finding specific susceptibility genes for them has not been straightf orward. The reasons are widely assumed to include lack of valid phenotypic definition\, absence of good theories of pathophysiology for candidate ge ne studies\, and the involvement of many genes\, each making small contrib utions to population risk. Within the last year or so\, a number of genome wide association (GWAS) of schizophrenia and BD have been published. Thes e have produced stronger evidence for association to specific risk loci th an have earlier studies\, specifically for the zinc finger binding protein 804A (ZNF804A) locus in schizophrenia and for the calcium channel\, volta ge-dependent\, L type\, alpha 1C subunit (CACNA1C) and ankyrin 3\, node of Ranvier (ANK3) loci in bipolar disorder. The ZNF804A and CACNA1C loci app ear to influence risk for both disorders\, a finding that supports the hyp othesis that schizophrenia and BD are not aetiologically distinct. In the case of schizophrenia\, a number of rare copy number variants have also be en detected that have fairly large effect sizes on disease risk\, and that additionally influence risk of autism\, mental retardation\, and other ne urodevelopmental disorders. The existing findings point to some likely pat hophysiological mechanisms but also challenge current concepts of disease classification. They also provide grounds for optimism that larger studies will reveal more about the origins of these disorders\, although currentl y\, very little of the genetic risk of either disorder is explained.\n\nSc hizophrenia genes\, gene expression\, and neuropathology: on the matter of their convergence.\n\nHarrison PJ\, Weinberger DR.\n\nMol Psychiatry. 200 5 Jan\;10(1):40-68\; image 5. Review. Erratum 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\nKirkbride JB & Jones PB\, 20 08\, The Mental Ill-Health of People Who Migrate and Their Descendants: Ri sk Factors\, Associated Disability and Wider Consequences. Mental Capital and Wellbeing Foresight State of Science Review SR-B13. Accessible from\n\ nhttp://www.foresight.gov.uk/OurWork/ActiveProjects/Mental%20Capital/Proje ctOutputs.asp LOCATION:Dept of Experimental Psychology END:VEVENT END:VCALENDAR