Transdiagnostic Neurobiological Biotypes of Trauma Timing: Data-driven approach of Childhood and Adulthood-Onset Trauma

Background: The developmental timing of trauma exposure may critically shape neurobiological outcomes, yet distinctions between childhood-onset trauma (CT) and adulthood-onset trauma (AT) remain poorly understood. Aim: This study explores whether trauma onset timing is associated with distinct resting-state functional connectivity (rsFC) pattern using data-driven approach. Methods: age=36.74 years) with post-traumatic stress disorder (PTSD), PTSD with major depressive disorder (MDD), and trauma-exposed healthy controls (TEHC) underwent resting-state fMRI. Of these participants, 15 with CT only, 17 with both CT and AT, and 47 with AT only. RsFC was calculated across the amygdala, hippocampus, nucleus accumbens (NAcc), the salience (SN), default mode (DMN), and frontoparietal networks (FPN). K-means clustering identified subgroups based on rsFC, with robustness assessed via bootstrapping, cross-validation, and replication using Gaussian Mixture Modeling. The identified clusters were compared on trauma timing, type, cumulative exposure, and clinical measures. Results: A two-cluster solution provided the most stable fit. The two generated clusters were significantly different in CT-only prevalence (p < 0.05; Cramér's V = 0.26, 95% CI). The CT cluster was marked by hyperconnectivity between amygdala-FPN, DMN-SN, NAcc-SN, and hippocampus-FPN relative to the AT cluster. Individuals with both CT and AT were evenly distributed across clusters. Clusters did not differ in PTSD or comorbid diagnoses, trauma type, or cumulative exposure. Conclusion: Data-driven clustering revealed distinct neurobiological profiles differentiating CT and AT. CT was associated with hyperconnectivity across salience, reward, and regulatory circuits, supporting developmental timing as a determinant of brain network organization in trauma-exposed populations.