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03-04 Genetic and genomic approaches to better understanding bipolar disorder

Published online by Cambridge University Press:  24 June 2014

PR Schofield,
IP Blair,
A Chetcuti,
EZ McAuley,
JM Fullerton,
JA Donald and
PB Mitchell
PR Schofield
Affiliation:
Prince of Wales Medical Research Institute, Sydney, New South Wales, AustraliaNeuroscience Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, AustraliaFaculty of Medicine, University of New South Wales, Sydney, New South Wales, AustraliaNeuroscience Institute for Schizophrenia and Allied Disorders, Sydney, NSW, Australia
IP Blair
Affiliation:
Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, AustraliaFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
A Chetcuti
Affiliation:
Prince of Wales Medical Research Institute, Sydney, New South Wales, AustraliaNeuroscience Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, AustraliaNeuroscience Institute for Schizophrenia and Allied Disorders, Sydney, NSW, Australia
EZ McAuley
Affiliation:
Prince of Wales Medical Research Institute, Sydney, New South Wales, AustraliaNeuroscience Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, AustraliaFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
JM Fullerton
Affiliation:
Prince of Wales Medical Research Institute, Sydney, New South Wales, AustraliaNeuroscience Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, AustraliaFaculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
JA Donald
Affiliation:
Neuroscience Institute for Schizophrenia and Allied Disorders, Sydney, NSW, Australia
PB Mitchell
Affiliation:
Department of Biological Sciences, Macquarie University, Sydney, New South Wales, AustraliaSchool of Psychiatry, University of New South Wales, Sydney, New South Wales, AustraliaBlack Dog Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia
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Abstract

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Information

Type
Abstracts from ‘Brainwaves’— The Australasian Society for Psychiatric Research Annual Meeting 2006, 6–8 December, Sydney, Australia
Information
Acta Neuropsychiatrica , Volume 18 , Issue 6 , December 2006, pp. 321
Copyright
Copyright © 2006 Blackwell Munksgaard

Background:

Bipolar affective disorder (BP) is a severe mood disorder characterized by alternating periods of mania and depression, with estimates of lifetime prevalence up to 4%.

Methods:

Studying BP families, genetic linkage analysis has been used to identify susceptibility loci. Positional cloning and association analysis was used to identify the susceptibility gene. Microarray analysis of gene expression profiles of mice treated with anti-manic drugs was performed.

Results:

The cadherin gene FAT was identified by positional cloning. Association with bipolar disorder was seen in two case-control cohorts with a family history of psychiatric illness, and in two cohorts of parent-proband trios where association was identified among bipolar cases who had exhibited psychosis. Pooled analysis further supported association (P = 0.0002, odds ratio = 2.31, 95% confidence interval: 1.49–3.59). Expression of FAT, and putative interacting proteins beta-catenin and the Ena/VASP proteins were investigated in mice following administration of the mood-stabilizing drugs, lithium and valproate. FAT was significantly downregulated (P = 0.027), and Catnb and Enah were significantly upregulated (P = 0.0003 and 0.005), in response to lithium. Expression of genes encoding murine homologs of the FAT-interacting proteins was investigated by microarray analysis, with eight genes showing significantly altered expression in response to lithium (binomial P = 0.004).

Conclusions:

Together, these data provide convergent evidence that FAT and its protein partners may be components of a molecular pathway involved in susceptibility to bipolar disorder. Genetic and genomics approaches may provide a means to better understanding the genes involved in BP onset and progression.