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GL.07 Dimensions or categories: what the new genetics tells us about neuropsychiatric disorders
  1. N Craddock

    Nick's research is focused on improving understanding of diagnosis and management of bipolar spectrum mood disorders and psychosis. As well as leading the Mood Disorders Research Team and the Bipolar Disorder Research Network (BDRN), Nick is also an honorary consultant psychiatrist at Cardiff University, and heads the Cardiff University Psychiatry Service. His clinical interests lie in the diagnosis and management of bipolar spectrum disorders. Nick is the scientific advisor for the MDF-The Bipolar Organisation. He advises BBC EastEnders on their bipolar disorder storyline and has contributed to many documentaries on bipolar disorder and psychiatry. Nick also appears on TV, Radio, and in the National Press on a regular basis. Nick has published more than 250 research articles and is a Fellow of the Academy of Medical Sciences. He Chairs the Academic Faculty of the Royal College of Psychiatrists and is an editorials editor for the British Journal of Psychiatry. He is Director of Mental Health Research and Development for Cardiff and Vale University Health Board.

Abstract

Mirroring clinical practice, it has been conventional for psychiatric research, including the search for predisposing genes, to proceed under the assumption that schizophrenia and bipolar disorder are separate disease entities with different underlying etiologies. These represent the traditional dichotomous classification of the so-called “functional” psychoses and form the basis of modern psychiatric diagnostic practice. Recent findings emerging in molecular genetic studies of psychoses show increasing evidence that challenges traditional classification categories. Within the context of the Wellcome Trust Case Control Consortium (WTCCC) we have studied 2700 mood-psychosis cases and 3000 controls and several other large-scale studies have been undertaken, including studies of structural genomic variation. The emerging evidence suggests the existence of both relatively specific as well as more general relationships between genotype and psychopathology. For example, in our dataset variation at GABAA receptor genes is associated with susceptibility to a form of illness with mixed features of schizophrenia and bipolar disorder. Genome-wide significant associations at CACNA1C in bipolar disorder and ZNF804A in schizophrenia show evidence for a contribution to susceptibility across the traditional diagnostic boundaries. Evidence from studies of structural genomic variation (copy number variation) suggests the need to reconsider the relationship between schizophrenia and childhood onset neurodevelopmental disorders, such as ADHD and autism. The elucidation of genotype-phenotype relationships is at an early stage, but current findings highlight the need to consider alternative approaches to classification and conceptualisation for psychiatric research, and perhaps, practice.

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