Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Apr 24;10(4):ENEURO.0109-21.2021.
doi: 10.1523/ENEURO.0109-21.2021. Print 2023 Apr.

The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review

Nikita S Persaud  1 , Hannah M Cates  2
Affiliations
Review

The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review

Nikita S Persaud et al. eNeuro. .

Abstract

Anxiety is one of the most common psychiatric disorders diagnosed in the United States today. Like all mental illnesses, anxiety pathology includes genetic, molecular, somatic, and behavioral characteristics. Specific brain regions implicated in anxiety include the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Together, these regions regulate fear-related learning and memory processes, and are innervated by neuronal projections that use glutamate and GABA as neurotransmitters. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are also implicated in anxiety. This review discusses the neuroepigenetics of the anxiety phenotype. While studying such changes is limited to postmortem brain studies or peripheral tissue acquisition in humans, the use of animals to model anxiety phenotypes has made epigenetic research possible. In this review, we summarize and discuss a plethora of DNA methylation, histone modification, and associated gene expression differences underscoring the anxiety phenotype. The findings we outline include expression changes of various DNA methyltransferases and changes in histone modifications that affect the hypothalamic pituitary adrenal axis and stress response as well as GABA, glutamate, and BDNF signaling in the PFC, amygdala, hypothalamus, and hippocampus. Furthermore, there have been studies showing that anxiety behaviors and biological scars from stress can be reversed using histone deacetylase inhibitors, and we discuss ideas for the future of treatment. In this review, we hope that by compiling much of the data pertaining to DNA methylation and histone modifications in vivo animal studies we are able to highlight potential avenues for future research despite existing limitations.

Keywords: DNA methylation; anxiety disorders; histone modifications; neuroepigenetics; review; rodent models.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interests.

Similar articles

See all similar articles

Cited by

References

    1. Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8:57–64. - PMC - PubMed
    1. Adachi M, Autry AE, Covington HE 3rd, Monteggia LM (2009) MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. J Neurosci 29:4218–4227. 10.1523/JNEUROSCI.4225-08.2009 - DOI - PMC - PubMed
    1. Alisch RS, Chopra P, Fox AS, Chen K, White AT, Roseboom PH, Keles S, Kalin NH (2014) Differentially methylated plasticity genes in the amygdala of young primates are linked to anxious temperament, an at risk phenotype for anxiety and depressive disorders. J Neurosci 34:15548–15556. 10.1523/JNEUROSCI.3338-14.2014 - DOI - PMC - PubMed
    1. Alisch RS, Van Hulle C, Chopra P, Bhattacharyya A, Zhang SC, Davidson RJ, Kalin NH, Goldsmith HH (2017) A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Transl Psychiatry 7:1282. - PMC - PubMed
    1. Anderson EM, Larson EB, Guzman D, Wissman AM, Neve RL, Nestler EJ, Self DW (2018) Overexpression of the histone dimethyltransferase G9a in nucleus accumbens shell increases cocaine self-administration, stress-induced reinstatement, and anxiety. J Neurosci 38:803–813. 10.1523/JNEUROSCI.1657-17.2017 - DOI - PMC - PubMed

LinkOut - more resources