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01-05-2015 | Original Article

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

Authors: Nathalie E. Holz, Arlette F. Buchmann, Regina Boecker, Dorothea Blomeyer, Sarah Baumeister, Isabella Wolf, Marcella Rietschel, Stephanie H. Witt, Michael M. Plichta, Andreas Meyer-Lindenberg, Tobias Banaschewski, Daniel Brandeis, Manfred Laucht

Published in: Brain Structure and Function | Issue 3/2015

Abstract

Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.

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Title: Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume
Authors: Nathalie E. Holz
Arlette F. Buchmann
Regina Boecker
Dorothea Blomeyer
Sarah Baumeister
Isabella Wolf
Marcella Rietschel
Stephanie H. Witt
Michael M. Plichta
Andreas Meyer-Lindenberg
Tobias Banaschewski
Daniel Brandeis
Manfred Laucht
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 3/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0729-5

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Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

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Other articles of this Issue 3/2015

An anterograde rabies virus vector for high-resolution large-scale reconstruction of 3D neuron morphology

A new window to understanding individual differences in reward sensitivity from attentional networks

Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound

Evidence for divergent effects of neurodegeneration in Huntington’s disease on attentional selection and neural plasticity: implications for excitotoxicity

Direct diffusion-based parcellation of the human thalamus

Anosognosia for obvious visual field defects in stroke patients