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Evaluating the evidence for a neuroimaging subtype of posttraumatic stress disorder

The search for neuroimaging and cognition-based subgroups of posttraumatic stress disorder illustrates the power and pitfalls of this approach. The intricate nature of PTSD Posttraumatic stress disorder (PTSD) is a psychiatric condition with heterogeneous symptoms and response to treatment. Patient stratification using noninvasive biomarkers could potentially result in more effective treatments and better outcome. A recent study used functional magnetic resonance imaging (fMRI) and identified a common signature associated with memory impairments in a subgroup of patients. Now, Esterman et al. used a similar approach in a cohort of patients and failed to replicate the results. However, the authors identified a cohort of patients with similar fMRI impairments but different cognitive features. The results suggest that patient stratification using fMRI and neuropsychological methods might require further consideration. A recent study used functional neuroimaging and cognitive tasks to identify posttraumatic stress disorder (PTSD) subtypes. Specifically, this study found that a subgroup of patients with verbal memory impairment had a unique neural signature, namely, decreased ventral attention network (VAN) resting-state functional connectivity, and these same individuals responded poorly to psychotherapy. Although this represents one of the first studies to propose a neurocognitive subtype of PTSD and has far-reaching translational potential, the generalizability and specificity of the observed neural network and cognitive domain remain unclear. We attempted to conceptually replicate and extend these findings in a similar cohort of combat-exposed veterans (n = 229) tested using a standardized battery of neuropsychological tests and a priori criteria for cognitive impairments. First, we conducted identical and complementary analyses to determine whether subjects with PTSD and neuropsychologically defined verbal memory deficits exhibited the VAN connectivity biomarker. Second, we examined whether cognitive deficits in other domains implicated in PTSD (executive functioning and attention) exhibited the VAN signature. Across multiple measures of verbal memory, we did not find that the subgroup of individuals with PTSD and memory impairments had lower VAN connectivity. However, a subgroup of individuals with PTSD and attentional impairments did have lower VAN connectivity, suggesting that the original subtype could have been related to attention and not memory impairments. Overall, our findings suggest that the previously identified memory-impaired PTSD subtype may not generalize. Further consideration of neuropsychological methods will be important for neurocognitive markers to be implemented clinically.