Evaluating the Evidence for Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma

Abstract

Objective: The weak link between subjective symptom-based diagnostic methods for posttraumatic psychopathology and objectively measured neurobiological indices forms a barrier to the development of effective personalized treatments. To overcome this problem, recent studies have aimed to stratify psychiatric disorders by identifying consistent subgroups based on objective neural markers. Along these lines, a promising 2021 study by Stevens et al. identified distinct brain-based biotypes associated with different longitudinal patterns of posttraumatic symptoms. Here, the authors conducted a conceptual nonexact replication of that study using a comparable data set from a multimodal longitudinal study of recent trauma survivors.

Methods: A total of 130 participants (mean age, 33.61 years, SD=11.21; 48% women) admitted to a general hospital emergency department following trauma exposure underwent demographic, clinical, and neuroimaging assessments 1, 6, and 14 months after trauma. All analyses followed the pipeline outlined in the original study and were conducted in collaboration with its authors.

Results: Task-based functional MRI conducted 1 month posttrauma was used to identify four clusters of individuals based on profiles of neural activity reflecting threat and reward reactivity. These clusters were not identical to the previously identified brain-based biotypes and were not associated with prospective symptoms of posttraumatic psychopathology.

Conclusions: Overall, these findings suggest that the original brain-based biotypes of trauma resilience and psychopathology may not generalize to other populations. Thus, caution is warranted when attempting to define subtypes of psychiatric vulnerability using neural indices before treatment implications can be fully realized. Additional replication studies are needed to identify more stable and generalizable neuroimaging-based biotypes of posttraumatic psychopathology.

Trial registration: ClinicalTrials.gov NCT03756545.

Keywords: Biological Markers; Neuroimaging; Neuroscience; Posttraumatic Stress Disorder (PTSD); Replication Study; Stress.

Figure 1.. Consort Diagram.

Flow chart depicting the inclusion and exclusion of participants in this report.

Figure 2.. fMRI Profiles of the Four Clusters among Recent Trauma Survivors (n=130).

Panel a show the region-of-interests (ROIs) covariance matrix revealing linear associations between z-scored contrast estimates extracted from the seven ROIs across the two fMRI tasks. For threat reactivity (‘T’), fMRI activation was extracted bilaterally from the amygdala (Amy), insula, dorsal and subgenual anterior cingulate cortex (dACC and sgACC, respectively) for the contrast of fearful > neutral faces. For reward reactivity (‘R’), bilateral activation was extracted from the nucleus accumbens (NAcc), amygdala (Amy) and orbitofrontal cortex (OFC) for the contrast of rewards > punishments. The matrix is ordered in the exact order as in Fig. 2 panels A and B in the original paper. Correlation coefficients (R-values) are indicated on a scale ranging from −1 (blue) to +1 (red). Panel b shows the dendrogram illustrating the final cluster solution with four clusters (marked by different colors). Panel c show Cluster differences (mean and standard deviation) for standardized contrast estimates extracted from the ROIs across the threat (fearful > neutral faces) and reward (rewards > punishments) contrasts.

Figure 3.. PTSD and Anxiety at 6-months Post-trauma among the Four Clusters of Recent Trauma Survivors (n=130).

Boxplots presenting the four clusters created based on neuroimaging data at 1-month post-trauma and their future clinical symptoms at 6-months post-trauma: Total scores of The Clinician‐Administered PTSD Scale (CAPS-4 in panel a; CAPS-5 in panel b), total scores of the PTSD Checklist List (PCL in panel c), and total scores of Beck Anxiety Inventory (BAI in panel d). T2 = 6-months following ED admission. *As requested, figures are uploaded to the system as separate files (PDF format). *Other exclusions (n=10): Serious medical condition requiring clinical attention (n=5), Chronic PTSD before current event (n=2), Current substance use disorder (n=1), Head injury (n=1), No traumatic event (n=1)