Can epigenetics shine a light on the biological pathways underlying major mental disorders?
Luis Alameda1,2, Giulia Trotta3, Harriet Quigley1
1Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Abstract:
A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the development of novel pharmacological treatments. Epigenetic mechanisms have emerged as mediators of environmental and genetic risk factors which might play a role in disease onset, including childhood adversity (CA) and cannabis use (CU). Particularly, human research exploring DNA methylation has provided new and promising insights into the role of biological pathways implicated in the aetio-pathogenesis of psychiatric conditions, including: monoaminergic (Serotonin and Dopamine), GABAergic, glutamatergic, neurogenesis, inflammatory and immune response and oxidative stress. While these epigenetic changes have been often studied as disease-specific, similarly to the investigation of environmental risk factors, they are often transdiagnostic. Therefore, we aim to review the existing literature on DNA methylation from human studies of psychiatric diseases (i) to identify epigenetic modifications mapping onto biological pathways either transdiagnostically or specifically related to psychiatric diseases such as Eating Disorders, Post-traumatic Stress Disorder, Bipolar and Psychotic Disorder, Depression, Autism Spectrum Disorder and Anxiety Disorder, and (ii) to investigate a convergence between some of these epigenetic modifications and the exposure to known risk factors for psychiatric disorders such as CA and CU, as well as to other epigenetic confounders in psychiatry research.
Insights
Epigenetic changes, like DNA methylation, are linked to mental illness pathways. This review explores these changes in psychiatric disorders and their connection to risk factors like childhood adversity and cannabis use.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Mental illnesses contribute significantly to the global disease burden.
- Understanding the biological pathways of mental illness onset is crucial for developing effective treatments and prevention strategies.
- Epigenetic mechanisms, particularly DNA methylation, are increasingly recognized as mediators between genetic and environmental risk factors in psychiatric disorders.
Purpose of the Study:
- To review human studies on DNA methylation in psychiatric diseases.
- To identify epigenetic modifications associated with transdiagnostic and specific psychiatric conditions.
- To investigate the convergence of these epigenetic modifications with risk factors such as childhood adversity and cannabis use.
Main Methods:
- Systematic literature review of human studies focusing on DNA methylation in psychiatric disorders.
- Analysis of epigenetic modifications related to biological pathways including monoaminergic, GABAergic, glutamatergic systems, neurogenesis, inflammation, immune response, and oxidative stress.
- Examination of associations between DNA methylation patterns and environmental risk factors like childhood adversity and cannabis use.
Main Results:
- DNA methylation alterations are implicated in the pathogenesis of various psychiatric conditions, often showing transdiagnostic patterns.
- Specific epigenetic modifications are linked to conditions such as Eating Disorders, PTSD, Bipolar Disorder, Psychotic Disorder, Depression, ASD, and Anxiety Disorder.
- Evidence suggests a convergence between certain DNA methylation changes and exposure to childhood adversity and cannabis use, highlighting potential epigenetic confounders.
Conclusions:
- DNA methylation provides valuable insights into the biological underpinnings of psychiatric disorders.
- Epigenetic modifications may serve as a bridge between environmental exposures and genetic predispositions in mental illness.
- Further research into DNA methylation patterns and their interplay with risk factors is essential for advancing psychiatric treatment and prevention.
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