Dataset Information

Neurocognitive Endophenotypes of Schizophrenia and Bipolar Disorder and Possible Associations with FKBP Variant rs3800373.

ABSTRACT: Introduction:Schizophrenia(SCZ) and Bipolar disorder (BD) are frequently occurring and impairing disorders that affect around 1% of the population. Important endophenotypes in the genetic research of SCZ and BD are cognitive functions. Core symptoms for SCZ and BD are impairments in working memory, declarative memory and attention, all of which fulfill the criteria for an endophenotype. The FK506 Binding Protein 5 (FKBP5) gene codes for a co-chaperone of the glucocorticoid receptor and has been reported to be associated with cognition. Aim:The aims of our research were to determine the degree of cognitive impairment in patients suffering from SCZ and BD and to explore the association of the FKBP5 variant rs3800373 genotype with the cognitive endophenotypes. Material and Methods:Patients and healthy controls were recruited over a period of two years from the Psychiatric Clinic, Clinical Center University of Sarajevo. Genotyping and neuropsychological assessments were performed for 263 subjects (129 SCZ, 53 BD, and 81 healthy controls [HC]). Neuropsychological assessments were performed for all patients with the Trail Making Test-A&B (TMT-A&B) and Digit-span forward&backwards tasks. The single nucleotide polymorphism (SNP) rs3800373 in the FKBP5 gene was genotyped using Infinium PsychArray Bead Chips. Results and Conclusion:SCZ and BD patients performed lower than HC in the TMT-A&B and in the Digit-span backwards task, while no differences were observed between SCZ and BD patients. While SCZ patients performed lower than HC in the Digit-span forwards task, there were no differences between BD and HC or between BD and SCZ. Rs 3800373 was not associated with performance in the TMT-A&B or Digit-span forwards&backwards tasks. SCZ and BD share largely overlapping neurocognitive characteristics. Rs3800373 was not associated with performance in the neuropsychological tests. However, given the limited sample size, the results do not exclude an association with the rs3800373 variant in a larger sample. Furthermore, as the analysis was limited to one SNP, the results cannot be generalized to other genetic variants in FKBP5.

SUBMITTER: Memic A

PROVIDER: S-EPMC6282916 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Neurocognitive Endophenotypes of Schizophrenia and Bipolar Disorder and Possible Associations with FKBP Variant rs3800373.

Memic Amra A Streit Fabian F Hasandedic Lejla L Witt Stephanie H SH Strohmaier Jana J Rietschel Marcella M Oruc Lilijana L

Medical archives (Sarajevo, Bosnia and Herzegovina) 20181101 5

<h4>Introduction</h4>Schizophrenia(SCZ) and Bipolar disorder (BD) are frequently occurring and impairing disorders that affect around 1% of the population. Important endophenotypes in the genetic research of SCZ and BD are cognitive functions. Core symptoms for SCZ and BD are impairments in working memory, declarative memory and attention, all of which fulfill the criteria for an endophenotype. The FK506 Binding Protein 5 (FKBP5) gene codes for a co-chaperone of the glucocorticoid receptor and h ...[more]

PMID: 30524168

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Project description:The role of genetic risk markers for Alzheimer's disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundació ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-?4 was significantly associated with the memory function NEs "delayed recall (DR)" (? = -0.76, p = 4.1 × 10-10), "learning" (? = -1.35, p = 2.91 × 10-6), and "recognition memory" (? = -0.58, p = 9.67 × 10-5); and with "DR" in the aMCI group (? = -0.36, p = 2.96 × 10-5). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-?4 was also significantly associated with the NE "learning" in individuals classified as having Pss-aMCI (? = -1.37, p = 5.82 × 10-5). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the "backward digits" working memory NE (? = 0.52, p = 7.57 × 10-5) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE "repetition" (? = -0.19, p = 5.34 × 10-6). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.

Dataset Information

Neurocognitive Endophenotypes of Schizophrenia and Bipolar Disorder and Possible Associations with FKBP Variant rs3800373.

Publications

Neurocognitive Endophenotypes of Schizophrenia and Bipolar Disorder and Possible Associations with FKBP Variant rs3800373.

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