The effect of childhood trauma on the severity of depressive symptoms and drug resistance in major depressive disorder - results from the international PROMPT study

Objectives: Treatment resistance in major depressive disorder (MDD) affects nearly 30% of patients, and early childhood trauma (CT) may play a significant role in its development. The international PROMPT project investigates the relationship between CT, the treatment outcome, and drug-resistance. Aim: This study assessed the impact of childhood trauma (CT) on depressive symptom severity and treatment response at baseline, week 8, and week 12, and examined predictors of treatment-resistant depression (TRD). It also investigated whether different approaches to calculating Childhood Trauma Questionnaire (CTQ) scores (categorical vs. quantitative) affect the results. Methods: The study included 168 patients from Phase 2 of the PROMPT cohort. The CTQ assessed five types of trauma: emotional (EA), sexual (SA) and physical abuse (PA), and emotional (EN) and physical neglect (PN). The Montgomery-& Aring;sberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) scales were used to evaluate the intensity of depressive symptoms. To investigate the associations between CT and treatment response, linear mixed-effects models (LMMs) were applied. Predictors of TRD were examined using multivariable logistic regression model. Results: Specific types of trauma correlated positively with depression severity in MADRS at certain follow-up points. Only quantitative approach for CTQ score confirmed a correlation between CTQ total score, EA and EN with intensity of depressive symptoms at baseline. Sexual abuse was associated with lower improvement at week 8, and emotional abuse with higher baseline severity and greater improvement at week 12; however, both associations lost significance after FDR correction. CTQ total score did not predict treatment-resistance. Age increased the risk of treatment-resistant depression by 33% over 10 years. Conclusions: Early childhood trauma, particularly emotional trauma, is associated with greater depression severity. Sexual and emotional abuse may show trends in their effects on treatment response. Age, but not childhood trauma, predicts treatment-resistant depression.