Neurobiological Signatures of Trauma, Personality, and Depressivity: A Transdiagnostic Machine Learning Study in Adolescents and Young Adults.

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Background Adolescence and early adulthood are vulnerable phases for psychiatric disorders, where trauma and personality development converge on shared and distinct, often unknown brain signatures.Methods We used Sparse Partial Least Squares (SPLS) to identify multivariate signatures between voxel-wise grey matter volume (GMV) and three domains: childhood trauma, personality, and depressivity. We performed structural equation modeling (SEM) among these domains, predicted functional outcome at 9-month follow-up via support vector machine classification, and correlated the SPLS signatures with resilience, coping and visual dysfunctions. All models were cross-validated in the discovery (n=633; 52.9% female, mean(SD) age=25.41(5.98) years) and validated in the replication sample (n=343; 53.0% female, 24.69(5.72) years) of the multi-site prospective PRONIA cohort, comprising individuals with recent-onset depression or psychosis, psychosis risk syndromes, and healthy controls.Results We identified three signatures of interest: (1) depressivity, linked to reduced GMV in limbic regions; (2) childhood trauma, associated with GMV in thalamic, frontotemporal, and parietal regions; (3) a trauma-personality-depressivity signature relating childhood trauma, personality, and depressivity, to GMV in thalamic, occipital, temporal, and limbic regions. Through SEM, childhood trauma was directly associated with depressivity and indirectly via a maladaptive personality structure. The trauma-personality-depressivity signature was the strongest predictor of poor functional outcome (BACDiscovery=75.8%, BACReplication=83.2%). The depressivity and trauma-personality-depressivity signatures were linked to deficient resilience and coping styles as well as visual dysfunctions.Conclusions Childhood trauma, personality, and depressivity are associated with shared and distinct brain signatures spanning the affective-psychotic spectrum. If these factors converge, current and future mental health may be compromised.

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