Cognitive effects of the ANK3 risk variants in patients with bipolar disorder and healthy individuals

Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals.

In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains.

Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals.

The sample size of patients with bipolar disorder was small, and most of the patients were on psychotropic medication.

These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder.