The Influence of Genetic Polymorphisms and Psychosocial Determinants on Suicidal Behaviors: A Case–Control Study of CRHR1, NTRK2, and FKBP5

Suicide, a major contributor to global mortality rates, especially among young patients, remains insufficiently integrated into public health initiatives despite notable progress in identifying its determinants. The prediction of suicidal behavior remains complex, often relying on subjective assessments rather than objective biomarkers. Single nucleotide polymorphisms (SNPs) such as rs110402 (<i>CRHR1</i> gene), rs3800373 (<i>FKBP5</i> gene), and rs2289656 (<i>NTRK2</i> gene) have been linked to physiological mechanisms involving stress response and activation of the hypothalamic-pituitary-adrenal (HPA) axis, which contributes to anxiety and stress regulation. This study aimed to assess stress-related gene polymorphisms in individuals with suicidal behavior compared to controls. According to our results, the presence of the A allele of rs2289656 was associated with a protective effect, while the GG genotype conferred a higher susceptibility to suicidal behaviors. Significant associations were observed between trauma and abuse history and the rs110402 polymorphism in <i>CRHR1</i> gene, highlighting a protective role for the GG genotype and increased predisposition to stress-related psychiatric conditions and suicidal behavior for A allele carriers. No valid associations were found for rs3800373 in the <i>FKBP5</i> gene, although suggestive trends related to depression and self-aggression were noted. Our findings underscore the need to identify reliable biomarkers associated with suicide risk, highlighting the importance of integrating hereditary and psychosocial data to better understand the underlying mechanisms and to support the development of effective early interventions.