DOI: 10.3390/jcm15208182 ISSN: 2077-0383

Dimension-Specific Childhood Maltreatment and Cross-Sectional Markers of Illness Burden in Treatment-Resistant Depression: A Retrospective Single-Center Study

Giacomo d’Andrea, Luca Persico, Arianna Rosati, Clara Cavallotto, Emilia Esposito, Alessia Santeusanio, Michela D’Angola, Ilenia Rosa, Lorenzo Pio Padula, Antonio Arrè, Corinna Bozzelli, Alessandra De Franco, Lorenzo Varrica, Gianfranco Tamagnini, Mauro Pettorruso, Giovanni Martinotti

Background/Objectives: We examined global and dimension-specific childhood maltreatment in relation to cross-sectional illness burden in treatment-resistant depression (TRD). Methods: This retrospective, single-center, case-only study included 104 records from November 2025 to June 2026. The Childhood Trauma Questionnaire–Short Form (CTQ-SF) was completed during TRD assessment. Primary outcomes were elapsed ongoing major depressive episode (MDE) duration and retrospectively reconstructed lifetime failed antidepressant-trial count; illness duration and previous MDEs were secondary. Models adjusted for age, sex, and extraction block; false discovery rate (FDR) correction covered 28 tests. Results: CTQ total and trauma load showed no significant linear associations. Per 5 points, physical abuse was associated with longer elapsed MDE duration (+50.3%; 95% CI, 24.0–82.2%; p < 0.001; q < 0.001) and more failed trials (IRR = 1.20; 95% CI, 1.10–1.30; p < 0.001; q < 0.001). Sexual abuse was associated with longer elapsed duration (+59.8%; 95% CI, 26.5–101.9%; p < 0.001; q = 0.001). Physical-abuse associations did not survive FDR correction in mutually adjusted subscale models; the failed-trial association also weakened after episode-duration adjustment. Emotional-neglect associations were inverse and require caution. Conclusions: These cross-sectional findings are hypothesis-generating and require prospective replication with standardized treatment histories and remission outcomes.

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