This review examined the current evidence for seven candidate genes—SLC6A4, MAOA, DRD2, DRD4, FKBP5, COMT, and BDNF—that have been proposed to influence psychiatric outcomes through interactions with environmental factors. Collectively, the literature shows that genetic variation can modify an individual’s biological response to stress, trauma, adversity, parenting, and substance exposure. However, the strength and reproducibility of these interactions differ substantially across genes and study populations.
The evidence indicates that gene–environment interactions are most consistently observed in pathways regulating neurotransmission, stress response, and neuroplasticity. While several candidate-gene associations have been replicated, many early findings have weakened following larger studies and meta-analyses, highlighting the limitations of single-gene approaches to psychiatric research.
Current psychiatric genetics supports a multifactorial model in which susceptibility to mental illness arises from the combined influence of numerous genetic variants, environmental exposures, developmental experiences, and epigenetic regulation. Rather than acting as deterministic causes, individual genes contribute modestly to biological vulnerability, with environmental factors influencing whether, when, and to what extent that vulnerability is expressed.
Overall, the evidence demonstrates that psychiatric disorders emerge from complex interactions between inherited genetic architecture and life experiences. Contemporary research therefore emphasizes polygenic risk, genome-wide analyses, and integrated biological models over single candidate-gene explanations, providing a more comprehensive framework for understanding psychiatric disease.