Present address: MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4
Article first published online: 16 JAN 2013
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 15, Issue 2, pages 215–222, March 2013
How to Cite
Drysdale, E., Knight, H. M., McIntosh, A. M. and Blackwood, D. H. (2013), Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4. Bipolar Disorders, 15: 215–222. doi: 10.1111/bdi.12040
ED and HMK contributed equally to this work.
- Issue published online: 25 FEB 2013
- Article first published online: 16 JAN 2013
- Received 16 August 2011, revised and accepted for publication 13 October 2012
- bipolar disorder;
- chromosome 4;
- genetic susceptibility;
Objectives: We studied cognitive function in high-risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High-risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor.
Methods: Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function.
Results: Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype-carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype.
Conclusions: Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high-risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.