title: Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression.
abstract: 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.
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden. Electronic address: alexandra.pantzar@ki.se.
authors: Alexandra
authors: A
authors: Pantzar
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden.
authors: Erika J
authors: EJ
authors: Laukka
authors: Bologna University, Bologna, Italy.
authors: Anna Rita
authors: AR
authors: Atti
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden; Max Planck Institute for Human Development, Berlin, Germany.
authors: Goran
authors: G
authors: Papenberg
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden; Karolinska Institutet, Department NVS, KI-Alzheimer Disease Research Center, Stockholm, Sweden.
authors: Lina
authors: L
authors: Keller
authors: Karolinska Institutet, Department NVS, KI-Alzheimer Disease Research Center, Stockholm, Sweden; Karolinska University Hospital, Department of Geriatric Medicine, Stockholm, Sweden.
authors: Caroline
authors: C
authors: Graff
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: Laura
authors: L
authors: Fratiglioni
authors: Aging Research Center, Karolinska Institutet and Stockholm University, Gävlegatan 16, 113 30 Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: Lars
authors: L
authors: Bäckman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D003866:Depressive Disorder / Q000150:complications* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics*; D061212:Memory, Episodic; D008875:Middle Aged; D009483:Neuropsychological Tests; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: C472551:CLSTN2 protein, human; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C513637:WWC1 protein, human
keywords: CLSTN2; Depression; Episodic memory; KIBRA; Old age