The role of MED22 and its transcriptional interactions with childhood trauma and trauma-focused psychotherapy in patients with major depressive disorder

The biological mechanisms linking childhood trauma (CT) to major depressive disorder (MDD) remain unclear. Expanding on previous research linking MED22 to CT in MDD, we examined three research questions: (1) MED22's role in the relationship between CT and MDD, considering genetic (GReX) and environmental (EReX) components of gene expression regulation; (2) associations between MED22 genetic variations and personality traits like neuroticism in 177 healthy volunteers; and (3) changes in MED22 expression over time in 22 MDD patients with CT undergoing trauma-focused psychotherapy, with clinical and blood assessments at baseline (T0), 4 (T4), 8 (T8), 12 (T12), and 24 weeks (T24). For the first question, in MDD patients, MED22 GReX was associated with neglect, sexual, and emotional abuse, while EReX was associated with neglect. For the second question, in healthy volunteers, MED22 SNPs were associated with higher neuroticism (Beta=0.2284; p-value=0.008), indicating reduced stress resilience. Finally, for the third question, psychotherapy improved depressive symptoms (p < 0.001) and decreased MED22 expression (F=3.05; p = 0.03), with a treatment response effect (F= 3.44; p = 0.02) at T12. Differences in MED22 expression between responders and non-responders were observed at T4 (z_value= -2.13; p = 0.040), T8 (z_value=-3.85; p = 0.0004), and T12 (z_value= -2.93; p = 0.007). Baseline transcript levels were positively associated with relapse (τ=0.390; p = 0.037) and were higher (p = 0.026) in non-remitters, suggesting potential for detecting relapse. MED22 reductions from T0 to T8 were associated with improved cognitive symptoms (τ= 0.345; p = 0.040). Transcript reductions at T12 were associated with improvements in neurovegetative (τ=0.362; p = 0.027) and anxiety symptoms (τ= 0.324; p = 0.040). Genetic and environmental factors may influence stress responses.