Genetic Susceptibility and Epigenetic Modifications in Anxiety and Mood Disorder

Poelmales Austin^*
*Correspondence: Poelmales Austin, Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil, Email:

Introduction

Anxiety and mood disorders, including Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD), Bipolar Disorder (BD), and related conditions, represent some of the most prevalent and debilitating mental illnesses globally. The World Health Organization (WHO) estimates that depression affects over 280 million people worldwide, while anxiety disorders affect over 260 million. These disorders are associated with significant personal, societal, and economic burdens, including impaired functioning, comorbidity with physical illnesses, and increased risk of suicide. While environmental factors such as trauma, stress, and socio-economic status are important contributors to these disorders, there is substantial evidence suggesting a strong biological underpinning, particularly genetic susceptibility and epigenetic modifications. Understanding the genetic architecture and epigenetic landscape of anxiety and mood disorders provides critical insights into their pathophysiology and offers the potential for precision medicine approaches. This article explores the role of genetic risk factors and epigenetic mechanisms in the etiology and progression of anxiety and mood disorders, highlighting key findings, emerging trends, and implications for diagnosis and treatment [1].

Description

Genetic susceptibility refers to the inherited predisposition of an individual to develop a certain disorder due to variations in their DNA. Family, twin, and adoption studies have long established that mood and anxiety disorders have a heritable component. For instance, the heritability of major depressive disorder is estimated to be around 37%, while bipolar disorder shows a heritability of approximately 70â??85%. Anxiety disorders also show moderate heritability, typically ranging between 30% and 50%. GWAS have revolutionized our understanding of the genetic basis of psychiatric disorders by identifying single nucleotide polymorphisms associated with disease risk across the genome. For mood and anxiety disorders, several risk loci have been discovered [2].

Earlier research focused on candidate genes involved in neurotransmitter systems, such as the serotonin transporter gene the dopamine transporter gene and Brain-Derived Neurotrophic Factor (BDNF). The SLC6A4 promoter region polymorphism, 5-HTTLPR, has been extensively studied and linked to depression risk, particularly in the context of environmental stress. However, candidate gene studies have faced criticism for poor reproducibility and methodological limitations. Therefore, emphasis has shifted towards hypothesis-free genome-wide approaches. PRS aggregate the effects of thousands of genetic variants to estimate an individualâ??s genetic liability to a disorder. While PRS for mood disorders are currently of limited predictive power for clinical use, they are valuable for research into gene-environment interactions and for stratifying individuals in prevention trials. There is substantial overlap in genetic risk across psychiatric disorders. For example, studies show shared genetic susceptibility between MDD, BD, schizophrenia, and anxiety disorders. This suggests common biological pathways, such as inflammation, neurodevelopment, and synaptic plasticity, underlie multiple mental health conditions [3].

Histone proteins package DNA into chromatin and their post-translational modifications (e.g., acetylation, methylation) influence gene accessibility. Altered histone acetylation patterns in prefrontal cortex and hippocampus tissues have been reported in postmortem studies of individuals with mood disorders, indicating disruption in genes involved in mood regulation and cognitive function. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs such as miR-124, miR-135, and miR-16 has been observed in both animal models and human patients with anxiety and depression. These miRNAs target genes in serotonin and inflammatory pathways [4].

Identifying specific genetic variants and epigenetic marks can help develop biomarkers for early diagnosis, disease subtyping, and treatment response prediction. Genetic and epigenetic profiling can guide individualized treatment plans, including selection of pharmacological agents (e.g., SSRIs, mood stabilizers) and non-pharmacological interventions. Emerging research on histone deacetylase inhibitors (HDACis) and DNA methyltransferase inhibitors (DNMTis) holds promise for reversing maladaptive epigenetic changes. However, challenges related to specificity and safety must be addressed. Interventions targeting modifiable environmental factors (e.g., stress reduction, early childhood support) may mitigate adverse epigenetic programming in at-risk individuals. Integrating genetic and epigenetic research into public mental health strategies can inform resource allocation, education, and screening programs [5].

Conclusion

Anxiety and mood disorders are complex conditions shaped by the intricate interplay of genetic predispositions and epigenetic modifications. Advances in genomics and epigenomics have illuminated key molecular mechanisms that contribute to individual differences in vulnerability, symptomatology, and treatment response. While challenges remain in translating these findings into clinical practice, the potential benefits are substantial. By embracing a multidimensional approach that integrates genetics, epigenetics, and environmental context, the mental health field is moving toward a future of precision psychiatry-where prevention, diagnosis, and treatment are tailored to the unique biological and experiential profile of each individual. Continued investment in research, interdisciplinary collaboration, and ethical oversight will be vital in harnessing these scientific insights for the betterment of mental health care worldwide.

Acknowledgement

None.

Conflict of Interest

None.

References

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