Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Abstract

Approximately 10%–30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010–.034; padj = .032–.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD.

Effects of a Dissociative Drug on Fronto-Limbic Resting-State Functional Connectivity in Individuals with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Study

“…Together, recent findings might imply that alterations in the fronto-limbic circuitry are highly context-dependent (Lebois et al 2022a) which limits their potential as neural markers of trauma-related dissociation. Hence, recent work has already started to explore the relationship of dissociation with alterations in neural networks related to consciousness, awareness of the bodily self, proprioception, and interoceptive awareness (Lanius et al 2018;Lebois et al 2021Lebois et al , 2022aWolf et al 2022) which might inform an updated conceptualization of dissociation in PTSD.…”

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study

“…Interestingly, this also converges with initial studies pointing towards effects of ketamine, a dissociation-inducing-drug, on prefrontal global functional connectivity (Abdallah et al 2017 , 2018 ; Castillo et al 2023 ; but see also Kraus et al 2020 ), stressing the potential of an in-depth exploration of prefrontal alterations during acute dissociative states. In a similar vein, recent work has already started to explore the relationship of dissociation with alterations in neural networks related to consciousness, awareness of the bodily self, proprioception, and interoceptive awareness (Lanius et al 2018 ; Lebois et al 2021 , 2022a , b ; Wolf et al 2023 ) which might inform an updated conceptualization of dissociation in PTSD.…”

Enhancing Agency in Posttraumatic Stress Disorder Therapies Through Sensorimotor Technologies

“…Emotional overmodulation (ie, hypoarousal) in D-PTSD is thought to be linked to an underactivation of the amygdala and an overactivation of the PFC [ 114 ], in contrast to the standard PTSD model. The Clinician-Administered PTSD Scale for DSM-5 [ 116 ] allows for differentiation between these 2 types of PTSD, and approximately 30% of individuals with PTSD may have the dissociative subtype [ 15 , 114 , 117 ]. It has already been demonstrated that patients with D-PTSD exhibit a higher proprioceptive drift in the RHI [ 15 ], suggesting that individuals with D-PTSD integrate the illusion more significantly due to their diminished SO.…”