Multimodal Associations of FKBP5 Methylation with Emotion-Regulatory Brain Circuits.

FKBP5 ambulatory assessment epigenetics prefrontal cortex stress

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
07 Mar 2024
Historique:
received: 16 08 2023
revised: 02 02 2024
accepted: 04 03 2024
medline: 10 3 2024
pubmed: 10 3 2024
entrez: 9 3 2024
Statut: aheadofprint

Résumé

Understanding the biological processes underlying individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. Yet it remains unclear how FKBP5 DNA methylation (DNAm) in peripheral blood relates to individual differences in measures of neural structure and function, and their relevance to daily-life stress responsivity. Here, we characterize multimodal correlates of FKBP5 DNAm by combining epigenetic data with neuroimaging and Ambulatory Assessment in a sample of 395 healthy individuals. First, we show that FKBP5 demethylation as a psychiatric risk factor relates to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex (vmPFC), a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional MRI scans during a well-established emotion processing task we find that FKBP5 DNAm in peripheral blood is associated with functional difference of prefrontal-limbic circuits modulating affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life. Overall, we demonstrate how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits.

Sections du résumé

BACKGROUND BACKGROUND
Understanding the biological processes underlying individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. Yet it remains unclear how FKBP5 DNA methylation (DNAm) in peripheral blood relates to individual differences in measures of neural structure and function, and their relevance to daily-life stress responsivity.
METHODS METHODS
Here, we characterize multimodal correlates of FKBP5 DNAm by combining epigenetic data with neuroimaging and Ambulatory Assessment in a sample of 395 healthy individuals.
RESULTS RESULTS
First, we show that FKBP5 demethylation as a psychiatric risk factor relates to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex (vmPFC), a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional MRI scans during a well-established emotion processing task we find that FKBP5 DNAm in peripheral blood is associated with functional difference of prefrontal-limbic circuits modulating affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life.
CONCLUSIONS CONCLUSIONS
Overall, we demonstrate how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits.

Identifiants

DOI: 10.1016/j.biopsych.2024.03.003 PMID: 38460581
pubmed: 38460581
pii: S0006-3223(24)01141-7
doi: 10.1016/j.biopsych.2024.03.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Thomas L Kremer (TL)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Junfang Chen (J)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Current address: Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine, School of Life Sciences, Fudan University, Guangzhou, China.

Anais Buhl (A)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Oksana Berhe (O)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Edda Bilek (E)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Lena Geiger-Primo (L)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Ren Ma (R)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Carolin Moessnang (C)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Current address: Faculty for Applied Psychology, SRH University Heidelberg, Heidelberg, Germany.

Markus Reichert (M)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mental mHealth Lab, Chair of Applied Psychology, Institute of Sports and Sports Science, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany; Department of eHealth and Sports Analytics, Ruhr University Bochum, Bochum, Germany.

Iris Reinhard (I)

Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Kristina Schwarz (K)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Current address: Institute of Clinical Psychology and Psychotherapy, Faculty of Psychology, Technische Universität Dresden, Dresden, Germany.

Janina I Schweiger (JI)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Fabian Streit (F)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Stephanie H Witt (SH)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Zhenxiang Zang (Z)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Current address: Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Xiaolong Zhang (X)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Markus M Noethen (MM)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.

Marcella Rietschel (M)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Ulrich W Ebner-Priemer (UW)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mental mHealth Lab, Chair of Applied Psychology, Institute of Sports and Sports Science, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.

Emanuel Schwarz (E)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Andreas Meyer-Lindenberg (A)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Urs Braun (U)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Heike Tost (H)

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: heike.tost@zi-mannheim.de.

Classifications MeSH