Abstract
Post-traumatic stress disorder (PTSD) is diagnosed clinically, yet similarly exposed individuals follow markedly different courses, and clinicians increasingly encounter claims that genetic, epigenetic, or social information can personalize assessment. This critical integrative review asks which of these factors is ready to inform clinical decisions. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to August 2026, prioritizing meta-analyses, large multi-cohort genomic and epigenomic studies, prospective cohorts, and externally validated prediction models. Genome-wide studies now implicate 95 risk loci and confirm a highly polygenic architecture, but no genetic, epigenetic, neuroendocrine, or inflammatory marker functions as a stand-alone diagnostic test. In contrast, trauma dose, childhood adversity, socioeconomic instability, social support, displacement, and occupational exposure are clinically actionable now for triage and follow-up planning, although they are not diagnostic evidence. This review proposes a four-tier bio-social calibration framework that separates exposure context, the validated clinical phenotype, research-grade biological adjuncts, and longitudinal monitoring, and that rejects adjusting diagnostic criteria by genotype or social profile. In current practice, structured trauma and social assessment with measurement-based follow-up is the evidence-supported approach; biological markers should remain research tools until they demonstrate incremental value, cross-ancestry calibration, and external validation.