The British Journal of Psychiatry (2009) 194: 527-534. doi: 10.1192/bjp.bp.107.047498
© 2009 The Royal College of Psychiatrists
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White matter microstructural impairments and genetic liability to familial bipolar I disorder

Christopher A. Chaddock, MA

Division of Psychological Medicine, Institute of Psychiatry, King's College London

Gareth J. Barker, PhD

Department of Clinical Neuroscience, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London

Nicolette Marshall, MSc and Katja Schulze, PhD

Division Of Psychological Medicine, Institute Of Psychiatry, King'S College London

Mei Hua Hall, PhD

Psychology Research Laboratory, McLean Hospital, Harvard Medical School, Massachusetts, USA

Adele Fern, BSc, Muriel Walshe, BA and Elvira Bramon, PhD

Division of Psychological Medicine, Institute of Psychiatry, King's College London

Xavier A. Chitnis, MSc

Department of Clinical Neuroscience, Centre for Neuroimaging Sciences, and Department of Biostatistics & Computing, Brain Image Analysis Unit, Institute of Psychiatry, King's College London

Robin Murray, FRCPsych, DSc

Division of Psychological Medicine, Institute of Psychiatry, King's College London

Colm McDonald, MRCPsych, PhD

Department of Psychiatry, National University of Ireland, Galway, Ireland.

Correspondence: Christopher Chaddock, Department of Psychiatry, PO 63, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. Email: chris.chaddock{at}iop.kcl.ac.uk

Declaration of interest

None.

Funding

C.C is supported by a Medical Research Council (MRC) Studentship. This study was supported by a MRC (UK) Pathfinder Award (C.M.). Additional individual funding included: Guy's & St Thomas' Charitable Foundation Research Studentship (K.S); postdoctoral award from the Department of Health (E.B.); and Taiwanese scholarship at King's College London (M.H.H.).

Background

Subtle abnormalities in frontal white matter have been reported in bipolar disorder.

Aims

To assess whether impaired integrity of white matter tracts is associated with bipolar disorder and genetic liability for the disorder.

Method

A total of 19 patients with psychotic bipolar I disorder from multiply affected families, 21 unaffected first-degree relatives and 18 comparison individuals (controls) underwent diffusion tensor imaging. Whole brain voxel-based analyses compared fractional anisotropy between patients and relatives with controls, and its relationship with a quantitative measure of genetic liability.

Results

Patients had decreased fractional anisotropy compared with controls in the genu of the corpus callosum, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. Increased genetic liability for bipolar disorder was associated with reduced fractional anisotropy across distributed regions of white matter in patients and their unaffected relatives.

Conclusions

Disturbed structural integrity within key intra- and interhemispheric tracts characterises both bipolar disorder and genetic liability for this illness.


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