Authors: Luis Alameda; Giulia Trotta; Harriet Quigley; Victoria Rodriguez; Romayne Gadelrab; Daniella Dwir; Emma Dempster; Chloe C. Y. Wong; Marta Di Forti · Research
Can Epigenetics Explain How Environmental Factors Influence Mental Health?
This review explores how epigenetic changes may mediate the effects of environmental factors like childhood adversity on mental health outcomes.
Source: Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y., & Di Forti, M. (2022). Can epigenetics shine a light on the biological pathways underlying major mental disorders? Psychological Medicine, 52, 1645–1665. https://doi.org/10.1017/S0033291721005559
What you need to know
- Epigenetic changes like DNA methylation may help explain how environmental factors influence risk for mental illness
- Many epigenetic changes associated with psychiatric disorders affect similar biological pathways across diagnoses
- Childhood adversity and cannabis use are linked to epigenetic changes in pathways relevant to mental health
- More research is needed to clarify how specific environmental exposures lead to epigenetic changes and increased psychiatric risk
How epigenetics links environment and mental health
Our genes play an important role in determining our risk for developing mental health conditions. However, environmental factors like childhood trauma or substance use also significantly impact this risk. But how exactly do life experiences “get under the skin” to affect our mental health? Epigenetics may provide some answers.
Epigenetics refers to changes in how our genes are expressed, without altering the underlying DNA sequence. Think of it like a dimmer switch for genes - epigenetic modifications can turn gene activity up or down. One of the most studied epigenetic processes is DNA methylation, which generally decreases gene expression.
Growing evidence suggests that environmental exposures can lead to epigenetic changes that may in turn increase risk for psychiatric disorders. This review examines the current state of epigenetics research in psychiatry, focusing on DNA methylation changes associated with major mental health conditions and environmental risk factors.
Key biological pathways affected across disorders
Studies have identified DNA methylation differences in several biological pathways across multiple psychiatric diagnoses:
Serotonin system
Serotonin is a neurotransmitter involved in mood regulation. Altered methylation of serotonin-related genes has been found in depression, bipolar disorder, and schizophrenia. For example, increased methylation of the serotonin transporter gene SLC6A4 is associated with depression and schizophrenia.
Dopamine system
Dopamine signaling plays a key role in reward and motivation. Studies have found methylation changes in dopamine receptor genes in schizophrenia. Some evidence also links dopamine-related methylation to eating disorders.
Glutamate/GABA balance
Glutamate and GABA are the main excitatory and inhibitory neurotransmitters in the brain. DNA methylation differences in genes related to glutamate and GABA signaling have been identified in schizophrenia, autism spectrum disorder, and depression.
Neuroplasticity and neurogenesis
These processes allow the brain to form new connections and generate new neurons. Methylation changes in genes involved in neuroplasticity, like BDNF, have been found across multiple disorders including schizophrenia, bipolar disorder, PTSD, depression, and autism.
Inflammation and immune function
Mounting evidence implicates inflammation in psychiatric disorders. Studies have identified methylation differences in immune-related genes in schizophrenia, depression, PTSD, and autism.
Stress response system
The hypothalamic-pituitary-adrenal (HPA) axis regulates our response to stress. Methylation changes in HPA-related genes have been associated with various disorders, often in connection with childhood adversity exposure.
The fact that many of these pathways are implicated across diagnostic categories suggests they may represent common biological mechanisms underlying different psychiatric symptoms. However, some methylation changes appear more specific - for example, dopamine-related changes are most consistently seen in psychotic disorders.
Epigenetic effects of environmental exposures
Childhood adversity
Exposure to childhood trauma and adversity is a major risk factor for multiple psychiatric disorders. Studies have found that childhood adversity is associated with DNA methylation changes in several of the biological systems mentioned above:
Serotonin: Increased methylation of the serotonin transporter gene SLC6A4 is linked to childhood adversity exposure and depression severity.
HPA axis: Childhood trauma is associated with methylation changes in stress response genes like NR3C1 and FKBP5 across various disorders.
Neuroplasticity: Adversity exposure is linked to altered methylation of BDNF and other neuroplasticity-related genes.
Inflammation: Some studies have found childhood adversity associated with methylation changes in immune genes.
These findings suggest epigenetic changes could potentially mediate the link between early life stress and later mental health problems. However, more research is needed to firmly establish causality.
Cannabis use
Cannabis use, especially heavy use in adolescence, is associated with increased risk for psychosis and other mental health issues. A few studies have examined epigenetic effects of cannabis:
Dopamine: Cannabis use is linked to methylation changes in dopamine receptor genes.
Endocannabinoid system: Altered methylation of cannabinoid receptor genes is seen with heavy cannabis use.
Neuroplasticity: Some evidence for cannabis-related methylation changes in genes involved in neurodevelopment.
While preliminary, these findings hint at potential biological mechanisms underlying cannabis-related psychiatric risk. More research in this area is warranted.
Conclusions
- Epigenetic research is shedding light on how environmental exposures may increase risk for mental illness through biological changes
- Many of the identified methylation changes affect similar pathways across diagnostic categories
- Childhood adversity appears to have widespread effects on methylation in stress response, neuroplasticity, and other relevant systems
- More studies are needed on timing of exposures, gene-environment interactions, and causal relationships in humans
Epigenetics is a promising area of research for understanding the complex interplay between genes, environment, and mental health. As the field progresses, it may lead to new approaches for prevention and treatment of psychiatric disorders. However, many questions remain to be answered before epigenetic findings can be translated into clinical applications.