Biological and neurocognitive correlates of comorbid post-traumatic stress disorder and alcohol use disorder: a systematic review

Clinical Snapshot

Key Findings

• P Value: Not applicable for systematic review

• Effect Size: Not quantified - narrative synthesis only

• Primary Outcome: Biological and neurocognitive correlates of comorbid PTSD and AUD

• Nnt Or Sensitivity: 72% genetic overlap between PTSD and AUD in female twins; DRD2 A1 allele and absence of APOE ε2 allele associated with comorbid condition

• Confidence Interval: Not provided

Clinical Application

Research findings not yet ready for clinical implementation Limited relevance to Australian civilian populations; may inform future research priorities for NHMRC funding and clinical guidelines development Limited applicability due to predominantly male veteran samples

Abstract

Background: Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur, leading to greater clinical burden than either disorder alone. Despite this, little is known about the biological pathways linking these two disorders.Objective: We conducted a systematic review to synthesize evidence on molecular, genetic, neural, and cognitive mechanisms contributing to comorbid PTSD & AUD.Method: Following PRISMA guidelines, we performed a comprehensive search of five databases using PTSD-related, AUD-related, biological, and neurocognitive terms. Participants had to meet diagnostic criteria for both PTSD and AUD, and studies were required to have a comparator including controls, PTSD only, or AUD only. A critical appraisal was completed for all studies.Results: From 3904 identified papers, 14 met the inclusion criteria. Four studies examined the same molecular marker, with three papers derived from the same cohort, investigating baseline and stress-induced cortisol and adrenocorticotropic hormone, and found no differences unique to PTSD & AUD. One study linked low brain-derived neurotrophic factor and hazardous drinking to PTSD onset over 2 years following hospital admission. Genetic studies showed considerable overlap (72%) between PTSD and AUD in female twins, whereby the DRD2 A1 allele and the absence of the APOE ϵ2 allele were strongly associated with PTSD and drinking. Studies also reported lower neurometabolites, white matter integrity, and hippocampal volume in PTSD & AUD. Critical appraisal of these studies highlighted prominent selection bias (predominantly male and veterans) and limited justification of sample size.Conclusions: These findings suggest that PTSD & AUD may be characterized by distinct neurobiological alterations and genetic vulnerabilities relative to comparator groups. However, as there are currently insufficient data to support or refute these findings, this highlights the need for further research. PTSD and AUD frequently co-occur, leading to greater clinical burden than either disorder alone. Despite this, little is known about the biological pathways linking these two disorders.The current study aimed to review the existing molecular, genetic, neural, and cognitive evidence, and suggests similar impacted stress regulation across PTSD-only, AUD-only, and PTSD & AUD, yet distinct neural and genetic substrates among individuals with PTSD & AUD.Future research should include more female participants and a broader range of trauma types (currently dominated by veteran samples), and use large-scale neuroimaging and genetic datasets to help to identify mechanisms underpinning PTSD & AUD.

References

1. 1.Towers, E. E., Hoffman, J., Louie, E. E., Dali, G., Logge, W., Mills, K., & Morley, K. C. (2026). Biological and neurocognitive correlates of comorbid post-traumatic stress disorder and alcohol use disorder: a systematic review. European Journal of Psychotraumatology, 17(1). https://doi.org/10.1080/20008066.2026.2640736