Neural substrates underpinning co-occurring posttraumatic stress disorder and alcohol use disorder

Abstract

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly prevalent and debilitating. Despite this, the neurobiology of comorbid PTSD & AUD remains poorly understood. To address this gap, this thesis aimed to investigate neural and psychological mechanisms that may represent risk factors for, or consequences of, co-occurring PTSD and AUD (PTSD & AUD).

Chapter 2 systematically reviewed the genetic, molecular, neural and cognitive mechanisms specific to PTSD & AUD. While evidence for greater hypothalamic-pituitary-adrenal axis dysregulation was limited, findings suggested potentially unique disruptions spanning genetic and neural domains, warranting further investigation.

Building on these findings, Chapters 3-5 used pooled neuroimaging datasets to examine the structural and functional underpinnings of PTSD & AUD. Chapters 3 and 4 represents the first large-scale investigation to directly compare current PTSD & AUD with PTSD-only, AUD-only, and controls. Using complementary region-specific and graph-theoretical approaches, these chapters identified shared and comorbidity-specific structural alterations. Chapter 5 identified altered intrinsic functional connectivity patterns associated with depression and stress symptom severity in PTSD & AUD relative to AUD-only.

Chapter 6 explored associations between negative affect, drinking motives, craving and use in a large Australian AUD sample with and without PTSD. Findings indicated that alcohol-related processes were more broadly linked to negative affect states (e.g., depression, stress, anxiety) in PTSD & AUD than AUD-only.

This thesis provides a comprehensive and highly integrated body of work examining the neural substrates of co-occurring PTSD and AUD and explores how psychological features relate to both clinical and neurobiological phenotypes. Findings suggest that PTSD & AUD is characterised by distinct neural and psychological alterations that may represent risk and/or maintenance mechanisms.