Psychological resilience and its genetic determinants: Insights from longitudinal analyses of surgery and trauma cohorts

Abstract

Abstract Background To identify resilience to trauma using longitudinal psychological assessments and uncover its genetic components. Methods This prospective cohort study included 12,946 surgical patients from the China Surgery and Anesthesia Cohort (CSAC) with assessments of depressive symptoms from pre-surgery through 1, 6, and 12 months post-surgery, using the 9-item Patient Health Questionnaire (PHQ-9). Linear mixed-effects models predicted post-surgery PHQ-9 scores; individuals with much lower observed PHQ-9 score than expected (i.e. lowest 25th percentile of residuals) were defined as resilient. We performed genome-wide association study (GWAS) analysis to identify variants associated with psychological resilience. We examined the identified variant in 2,285 patients from the China Severe Trauma Cohort (CSTC) using genotype stratification and additive models. Results CSAC participants had a mean age of 52.2 years and 58.5% were female. Overall, 2,328 (18.0%) were identified as resilient and exhibited a lower prevalence of psychological symptoms. GWAS identified a lead single-nucleotide polymorphism (rs11766511, P = 3.082 × 10−8) mapped to the gene sidekick cell adhesion molecule 1 (SDK1), as a candidate locus implicating neural signaling pathways in stress response and resilience. In CSTC, genotype stratification suggested a lower symptom burden among GG genotype of rs11766511 compared with AA carriers (e.g. Beta = −0.94 [−1.76 to −0.12] for PHQ-9 score). The additive genetic model showed a directionally consistent but non-significant protective pattern of the G allele across psychological symptoms. Conclusions Longitudinal assessments of depressive symptoms offer a reliable method for measuring psychological resilience. The rs11766511 locus mapped to SDK1 may represent a candidate genetic signal for psychological resilience and warrants confirmation.