THE IMPACT OF CHILDHOOD TRAUMAS ON RESPONSE TO ACCELERATED RTMS IN TREATMENT-RESISTANT DEPRESSION

Abstract Background Childhood traumas have long been recognized as pivotal determinants in the progression and severity of depressive disorders, especially in treatment-resistant depression (TRD). These early life adversities can induce distinct neurostructural and functional alterations, potentially mediating the responsiveness to antidepressant therapies. Aims & Objectives To evaluate the interplay between childhood traumas and treatment outcomes in TRD patients undergoing an accelerated repetitive transcranial magnetic stimulation (arTMS) regimen. Methods In this multicentric, prospective analysis, we enrolled 51 TRD patients (average age 56±13.305; M/F=28/23) involved in an intensive arTMS protocol— comprising 4 daily sessions over 5 consecutive days, targeting the Left Dorsolateral Prefrontal Cortex at High Frequency/10 Hz. Comprehensive psychiatric evaluations were performed, employing the MADRS scale to chronicle depressive symptoms at various stages (baseline/T0, one week/T1, and a month/T2 post-treatment) and the CTQ scale (at T0) to quantify exposure to traumas during early life. CTQ scores guided the bifurcation of patients into two cohorts: those minimally exposed to childhood traumas (Low_Trauma) and their highly exposed counterparts (High_Trauma). We developed a General Linear Model (GLM), implementing repeated measures ANOVA (rm-ANOVA), to discern the interplay between temporal shifts (T0vsT1vsT2) and trauma exposure groups. Results Our rm-ANOVA underscored a marked improvement in MADRS scores from T0 through T1 to T2 (F98,2=73.938; P<0.001), attesting the robust efficacy of the arTMS modality. Intriguingly, there emerged a pronounced interaction between the temporal trajectory and trauma exposure groups (Low_trauma vs. High_Trauma) (F98,2=5.980; P=0.004). Subsequent analyses elucidated a more pronounced symptom amelioration in the Low_Trauma cohort. Notably, the comparative efficacy was markedly elevated in the group with lesser traumatic experiences (Cohen’ s d: 2.164 vs. 1.204), underscoring the potential inhibitory role of extensive childhood trauma on therapeutic outcomes. Discussion & Conclusions Early-life traumatic events seemingly interface with distinct neural networks, potentially resistant to modulation by the arTMS protocol. Such profound traumas during formative years could thus emerge as a harbinger of suboptimal treatment outcomes. A deeper exploration into TMS's neurophysiological dynamics and trauma's psychobiological underpinnings might pave the way for a better therapeutic approach, clinically-oriented, for TRD patients.