Investigation of the CADM2 polymorphism rs17518584 in memory and executive functions measures in a cohort of young healthy individuals.

The common polymorphism rs17518584, near the cell adhesion molecule 2 gene (CADM2), was previously identified as playing a role in information processing speed in a genome-wide association study of executive functions and processing speed performed in a cohort of non-demented older adults. In this study, we investigated this polymorphism in a younger population cohort (≤30 years old, median age 19 years), with no known memory or psychiatric disorders, for which we had phenotyped all participants for memory function (n = 514), and a subset of the participants for executive functions (n = 338), using a battery of tests measuring visuo-spatial memory, working memory, verbal memory, and frontal lobe functions (visual scanning, graphomotor speed, and cognitive flexibility). The polymorphism rs17518584 was genotyped by a restriction fragment length polymorphism assay and analysis indicated that the CADM2 polymorphism showed evidence of association with information processing speed as inferred from scores from the Stroop Word, Colour, and Colour-Word Tests (p = 0.005, p = 0.04, and p = 0.028, respectively, in a dominant inheritance model), as well as Trail Making Test Part A (p = 0.005 in an additive model). Significant associations of rs17518584 with scores from other tests of memory subtypes were not detected. The findings of this study provide further support for a role of CADM2 in aspects of cognitive function, in particular reading and information processing speed, and suggest that this role extends to younger individuals.

A CREB1 Gene Polymorphism (rs2253206) Is Associated with Prospective Memory in a Healthy Cohort.

Prospective memory (PM) is generally defined as remembering to perform intended actions in the future and is important for functioning in daily life. Cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB1) plays an important role in cognitive functions. In this study, we hypothesized that genetic variation in the CREB1 gene is associated with PM. We genotyped a CREB1 promoter polymorphism rs2253206 and tested it for association with PM in 619 healthy subjects. PM performance was measured using the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM), and the Memory for Intentions Screening Test (MIST). Generalized linear model analysis was conducted for each PM test independently using different inheritance models to identify any associations (p < 0.05). After multiple testing adjustments, a significant association was found between the rs2253206 genotype and PM performance for CAPM instrumental activities of daily living measure (p = 0.016). These results suggest that the rs2253206 polymorphism in the CREB1 gene locus is associated with PM in healthy individuals and contributes to knowledge on the genetics of this particular type of memory.

BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort.

Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory (p-value = 0.003) in a small cohort (n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance.

Working memory dysfunctions predict social problem solving skills in schizophrenia.

The current study aimed to examine the contribution of neurocognition and social cognition to components of social problem solving. Sixty-seven inpatients with schizophrenia and 31 healthy controls were administrated batteries of neurocognitive tests, emotion perception tests, and the Chinese Assessment of Interpersonal Problem Solving Skills (CAIPSS). MANOVAs were conducted to investigate the domains in which patients with schizophrenia showed impairments. Correlations were used to determine which impaired domains were associated with social problem solving, and multiple regression analyses were conducted to compare the relative contribution of neurocognitive and social cognitive functioning to components of social problem solving. Compared with healthy controls, patients with schizophrenia performed significantly worse in sustained attention, working memory, negative emotion, intention identification and all components of the CAIPSS. Specifically, sustained attention, working memory and negative emotion identification were found to correlate with social problem solving and 1-back accuracy significantly predicted the poor performance in social problem solving. Among the dysfunctions in schizophrenia, working memory contributed most to deficits in social problem solving in patients with schizophrenia. This finding provides support for targeting working memory in the development of future social problem solving rehabilitation interventions.