Affiliation:
1. Department of Psychiatry and Psychotherapy, Medical Center, University of Freiburg, Faculty of Medicine, University
of Freiburg, Germany
2. Department of Chromation Regulation, Max Planck Institute of Immunobiology and Epigenetics,
Freiburg, Germany
3. Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg,
Germany
Abstract
Abstract:
Fear-, anxiety- and stress-related disorders are among the most frequent mental disorders.
Given substantial rates of insufficient treatment response and often a chronic course, a better understanding
of the pathomechanisms of fear-, anxiety- and stress-related disorders is urgently warranted.
Epigenetic mechanisms such as histone modifications - positioned at the interface between the biological
and the environmental level in the complex pathogenesis of mental disorders - might be highly informative
in this context. The current state of knowledge on histone modifications, chromatin-related
pharmacology and animal models modified for genes involved in the histone-related epigenetic machinery
will be reviewed with respect to fear-, anxiety- and stress-related states. Relevant studies, published
until 30th June 2022, were identified using a multi-step systematic literature search of the Pub-
Med and Web of Science databases. Animal studies point towards histone modifications (e.g.,
H3K4me3, H3K9me1/2/3, H3K27me2/3, H3K9ac, H3K14ac and H4K5ac) to be dynamically and
mostly brain region-, task- and time-dependently altered on a genome-wide level or gene-specifically
(e.g., Bdnf) in models of fear conditioning, retrieval and extinction, acute and (sub-)chronic stress.
Singular and underpowered studies on histone modifications in human fear-, anxiety- or stress-related
phenotypes are currently restricted to the phenotype of PTSD. Provided consistent validation in human
phenotypes, epigenetic biomarkers might ultimately inform indicated preventive interventions as well
as personalized treatment approaches, and could inspire future innovative pharmacological treatment
options targeting the epigenetic machinery improving treatment response in fear-, anxiety- and stressrelated
disorders.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine
Cited by
4 articles.
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