Brain structural covariance networks in co-occurring PTSD and alcohol use disorder: An ENIGMA PTSD and ENIGMA addiction working group collaboration.

High rates of comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) may stem from a shared neurobiological basis; however, research exploring this overlap remains limited. We examined whole-brain structural covariance (SC) across PTSD, AUD, comorbid PTSD & AUD, trauma-exposed controls, and trauma-naïve controls to identify shared and unique SC profiles. Structural brain scans were acquired from individuals across 14 sites (N = 1565), and cortical thickness estimates were extracted to compute SC. Group differences in SC between pairs of cortical regions were examined using the Network-Based statistic and quantified using local and global graph theory (GT) measures. Clinical groups showed consistent alterations in SC compared with trauma-naïve controls, characterised by lower SC involving frontal regions, particularly the inferior frontal gyrus and frontal pole, which also demonstrated high centrality in local GT analyses. In contrast, higher SC was observed in temporal regions, with the fusiform gyrus consistently emerging as a central region. Comparisons involving PTSD & AUD also showed increased SC in occipital regions, suggesting a potentially distinct pattern of structural organization in this group. Global GT analyses demonstrated altered network organization in clinical groups, including increased clustering and path length, and reduced global efficiency relative to trauma-naïve controls. Local efficiency was increased in PTSD and PTSD & AUD, but not AUD alone. Together, these findings indicate that alterations in frontal and temporal regions are implicated across PTSD, AUD, and their comorbidity. However, the PTSD & AUD group also exhibited additional occipital lobe alterations, suggesting a broader distribution of structural covariance alterations in the comorbid group.