Cognitive–behavioural therapy (CBT) is a first-line treatment for depressive disorders, but research on its neurobiological mechanisms is limited. Given the heterogeneity in CBT response, investigating the neurobiological effects of CBT may improve response prediction and outcomes.

To examine brain functional changes during negative emotion processing following naturalistic CBT.

In this case-control study, 59 patients with depressive disorders were investigated before and after 20 CBT sessions using a negative-emotion-processing paradigm during functional magnetic resonance imaging, clinical interviews and depressive symptom questionnaires. Healthy controls (n = 60) were also assessed twice within an equivalent time interval. Patients were classified into subgroups based on changes in diagnosis according to DSM-IV criteria (n = 40 responders, n = 19 non-responders). Brain activity changes were examined using group × time analysis of variance for limbic areas, and at the whole-brain level.

Analyses yielded a significant group × time interaction in the hippocampus (P family-wise error [PFWE] = 0.022, ηP2 = 0.101), and a significant main effect of time in the dorsal anterior cingulate cortex (PFWE = 0.043, ηP² = 0.098), resulting from activity decreases following CBT (PFWE ≤ 0.024, ηP² ≤ 0.233), with no changes in healthy controls. Hippocampal activity decreases were driven by responders (PFWE ≤ 0.020, ηP² ≤ 0.260) and correlated with symptom improvement (r = 0.293, P = 0.024). Responders exhibited higher pre-treatment hippocampal activity (PFWE = 0.017, ηP² = 0.189).

Following CBT, reduced activity in emotion-processing regions was observed in patients with depressive disorders, with hippocampal activity decreases linked to treatment response. This suggests successful CBT could correct biased emotion processing, potentially by altering activity in key areas of emotion processing.Hippocampal activity may function as a predictive marker of CBT response.

Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.

We addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.

A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.

These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.