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

Anxiety is one of the most common psychiatric disorders diagnosed in the USA 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 utilize glutamate and gamma-aminobutyric acid (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 post-mortem 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.Findings we outline include expression changes of various DMNTs 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 HDAC 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, that we are able to highlight potential avenues for future research despite existing limitations.