Childhood maltreatment is linked to transdiagnostic age- and sex-specific cortical thinning and reduced amygdalar volume in young adults.

Childhood maltreatment is a transdiagnostic risk factor, whose distributed neural correlates are most timely and urgently assessed in young adults in the earliest stages of emerging mental disorders. Here, we applied a data-driven multivariate approach to identify distributed brain structural signatures associated with childhood maltreatment, with a particular focus on limbic regions, and to examine their relevance for later functional outcomes. In a transdiagnostic sample of 251 individuals (mean age 24.9 ± 4.3, 51.8% male) with early affective or anxiety syndromes, we used a multivariate sparse partial least squares algorithm to investigate multi-layered associations between grey-matter volume and the Childhood Trauma Questionnaire. We identified signatures linking age-dependent physical abuse and minimization/denial to widespread cortical thinning (ρ=0.424, p=.007; R2 = 18%), as well as female-specific emotional abuse to smaller left amygdala nuclei (ρ =0.566, p=.014; R2 = 32% shared variance). In females, emotional abuse predicted poorer functioning at 1- (β=-0.45, p<.001) and 2-year (β=-0.48, p<.001) follow-up, while smaller amygdala nuclei predicted better outcomes at 2 years (β=0.26, p=.04), although sensitive to including baseline functioning (β=0.17, p=.071). Support-vector machine (SVM) analyses further showed that females with higher trauma-related loadings and larger left amygdala nuclei could be identified using clinical features, although only in the extreme tertile split (BAC=69.2%, p=.038, AUC=0.62, 95%-CI=0.40-0.84). These findings suggest that trauma-reactive amygdala alterations may reflect heterogeneous sex-specific adaptation trajectories. This highlights the potential of age-, sex-, and trauma type-sensitive assessment at the earliest point of care, and proposes that early identification of such neurobiological signatures can inform more individualised approaches to treatment and recovery.