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Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

ABSTRACT: In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive performance on a block design (BD) and delayed auditory verbal task (AVLT). We also investigated whether the putative interaction was different for patients with a psychotic disorder (n?=?89) compared to their non-psychotic siblings (n?=?95), in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered.

SUBMITTER: Hernaus D

PROVIDER: S-EPMC3962453 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

Hernaus Dennis D van Winkel Ruud R Gronenschild Ed E Habets Petra P Kenis Gunter G Marcelis Machteld M van Os Jim J Myin-Germeys Inez I Collip Dina D

PloS one 20140321 3

In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target un ...[more]

PMID: 24658422

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Project description:The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

Dataset Information

Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

Publications

Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

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