Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression

The KIBRA (rs17070145) C-allele and the CLSTN2 (rs6439886) T-allele have both been associated with poorer episodic memory performance. Given that episodic memory is affected in depression, we hypothesized that the combination of these risk alleles would be particularly detrimental to episodic memory performance in depressed persons. In the population-based SNAC-K study, 2170 participants (≥ 60 years) without dementia (DSM-IV criteria) and antidepressant pharmacotherapy were clinically examined and diagnosed following ICD-10 criteria for unipolar depression, and genotyped for KIBRA and CLSTN2. Participants were categorized according to unipolar depression status (yes, no) and genotype combinations (KIBRA: CC, any T; CLSTN2: TT, any C). Critically, a three-way interaction effect showed that the CC/TT genotype combination was associated with poorer episodic recall and recognition performance only in depressed elderly persons, with depressed CC/TT carriers consistently performing at the lowest level. This finding supports the view that effects of genetic polymorphisms on cognitive functioning may be most easily disclosed at suboptimal levels of cognitive ability, such as in old-age depression.