Resting-state connectivity subtype of comorbid PTSD and alcohol use disorder moderates improvement from integrated prolonged exposure therapy in Veterans

Abstract

Background: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy.

Methods: In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment.

Results: We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption.

Conclusions: Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

Keywords: Alcohol use disorder; PTSD; biomarkers; fMRI; network connectivity; treatment prediction.

Figure 1.

S-GIMME identified common and unique effective connectivity. (A) S-GIMME group-level effective connectivity paths. Paths represent connections common to most subjects (red arrows). Green border on arrow represents path significantly greater for Subgroup 1. Yellow border on arrow represents path significantly greater for Subgroup 2. (B) Subgroup 1 was further characterized by two effective connectivity paths: putamen to pMCC, and IPC to MFG (green arrows). (C) Subgroup 2 was characterized by one additional effective connectivity path: pgACC to IPC (yellow arrows). Auto-regressive and lagged paths are not shown.

Figure 2.

Connectivity Subgroup differences in group-level paths. Subgroup 1 had a greater insula to IPC path compared to Subgroup 2. Subgroup 2 had a greater pgACC to pMCC path compared to Subgroup 1. * = ps < .004 (uncorrected) and ps_FDR < .02. See online version for color.

Figure 3.

Connectivity cluster moderated psychotherapy outcome for PTSD symptoms. (A) Clinician Administered PTSD Scale for DSM-5 (CAPS-5) total severity scores (estimated marginal means) for Pre- and Post-treatment assessments. Connectivity subgroup 2 showed a bigger change in PTSD symptoms than subgroup 1 in the I-PE groups: subgroup × time interaction, * p = .041. (B) Percentage of Heavy Drinking Days (PHDD) for Pre- and Post-treatment assessments (estimated marginal means). Connectivity subgroup did not impact improvement in drinking symptoms assessed using the PHDD. See online version for color.