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Multimodal Associations of FKBP5 Methylation with Emotion-Regulatory Brain Circuits

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机构： [1]Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. [2]Current address: Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine, School of Life Sciences, Fudan University, Guangzhou, China. [3]Current address: Faculty for Applied Psychology, SRH University Heidelberg, Heidelberg, Germany. [4]Mental mHealth Lab, Chair of Applied Psychology, Institute of Sports and Sports Science, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany. [5]Department of eHealth and Sports Analytics, Ruhr University Bochum, Bochum, Germany. [6]Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. [7]Current address: Institute of Clinical Psychology and Psychotherapy, Faculty of Psychology, Technische Universität Dresden, Dresden, Germany. [8]Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. [9]Current address: Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China. [10]Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany. [11]Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.

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关键词： FKBP5 epigenetics prefrontal cortex stress ambulatory assessment

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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.Copyright © 2024. Published by Elsevier Inc.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区神经科学 1 区精神病学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区神经科学 1 区精神病学

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第一作者机构： [1]Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

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Multimodal Associations of FKBP5 Methylation with Emotion-Regulatory Brain Circuits

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