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Association between genotype at an exonic SNP in DISC1 and normal cognitive aging.

Thomson PA, Harris SE, Starr JM, Whalley LJ, Porteous DJ, Deary IJ

Medical Genetics Section, Department of Medical Sciences, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK. pippa.thomson@ed.ac.uk

DISC1 is expressed in the hippocampus and has been identified as a possible genetic risk factor for both schizophrenia and bipolar disorder. These psychiatric illnesses are associated with impaired learning and memory. This study investigates the association of variation in DISC1 with cognitive function on the same general mental ability test (Moray House Test) at age 11 and age 79, and cognitive change between ages 11 and 79, in 425 people from the Lothian Birth Cohort 1921 (LBC1921). Tests of memory, non-verbal reasoning and executive function were also administered at age 79. The effect of genotype at a non-synonymous single nucleotide polymorphism in exon 11, rs821616, was studied. There was no direct effect of DISC1 genotype on any cognitive measure. However, there was a significant DISC1 genotype by sex interaction on Moray House Test scores at age 79, both before and after adjustment for cognitive ability at age 11 (p = 0.034 and 0.043, respectively). Women homozygous for the Cys allele had significantly lower cognitive ability scores than men at age 79, p = 0.003. Variation in DISC1 may therefore affect cognitive aging especially in women.

Published 2 September 2005 in Neurosci Lett, 389(1): 41-5.
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