The Impact of the CACNA1C Risk Allele on Cognitive Functioning in Euthymic Type I Bipolar Disorder

Abstract

Introduction: Bipolar disorder (BD) is a genetically heritable mood disorder typically characterized by manic and depressive episodes. Cognitive impairments experienced by people with BD are one of the best predictors of functional capacity in their daily lives. There are notable impairments in various domains, such as executive functioning, working memory, and processing speed, in both individuals diagnosed with BD as well as their first-degree unaffected relatives, which emphasizes the important role genetic factors play in the onset and presence of cognitive impairments. One commonly studied single nucleotide polymorphism (SNP) associated with BD and cognition is the CACNA1C rs1006737 SNP. Although there have been numerous studies investigating the effects of rs1006737 on cognitive functioning in BD, results have been inconclusive and mixed. Thus, we examined the involvement and impact of the CACNA1C rs1006737 risk SNP on cognitive functioning in the domains of executive functioning, working memory, and processing speed. Methods: A total of 70 euthymic BD-I participants and 76 healthy control (HC) participants were assessed on the cognitive domains of executive functioning, working memory, and processing speed and genotyped for the CACNA1C rs1006737 risk SNP. Results: No significant differences were observed in the scores for the cognitive domains of executive functioning, working memory, and processing between BD risk carriers vs. non-risk homozygotes, HC risk carriers vs. non-risk homozygotes, BD and HC risk carriers, and BD and HC non-risk homozygotes. Conclusion and Future Directions: The results suggest that the rs1006737 risk SNP does not have a significant impact on the cognitive domains investigated in BD and HC. However, our small sample size and lack of an age-matched control group are crucial limitations that must be taken into consideration. Future studies with larger sample sizes can help to further elucidate the role the CACNA1C rs1006737 risk SNP plays in cognitive functioning in BD.