Childhood adversity and multi-dimensional cognitive dysfunction in major depressive disorder: investigating heterogeneous effects across gender and educational in the UK Biobank

Major Depressive Disorder (MDD) is characterized by cognitive dysfunction that persists as one of the most profoundly disabling mental health conditions worldwide. Childhood adversity (CA) is not only a significant risk factor for the onset and course of MDD, but it is also strongly linked to decreased cognitive performance in MDD. Existing studies feature small sample sizes, single evaluation indicators, inconsistent outcomes, and few studies on the effects of demographic variables. This study used cross-sectional data (N = 2353) from the UK Biobank to investigate the relationship between childhood adversity (CA) and multi-dimensional cognitive function in patients with major depressive disorder (MDD), as well as the moderating effects of demographic variables. A generalized linear model was used to assess the relationships between five types of CA (physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse), as well as cumulative adversity scores, and multi-dimensional cognitive tests (fluid intelligence, reaction time, and pairs matching test). The findings revealed that higher scores of physical abuse (β=-0.420, 95% CI=-0.729 to 0.111, P = 0.008), physical neglect (β=-0.578, 95% CI=-0.922 to -0.235, P = 0.001) and cumulative adversity (β=-0.169, 95% CI=-0.272 to -0.066, P = 0.001) were substantially associated with poorer fluid intelligence, whereas emotional abuse (β = 0.285, 95% CI = 0.020 to 0.549, P = 0.035) and physical neglect (β = 0.328, 95% CI = 0.020 to 0.636, P = 0.037) were associated with poorer performance on the pairs matching test. The stratified analysis demonstrated that the adverse impact of childhood adversity on cognitive function was exacerbated among female patients, while there was no discernible correlation in male patients. Highly educated patients showed poorer fluid intelligence while less educated patients showed poorer pair matching. The study reveals that the influence of childhood adversity on cognition is not uniform but is instead shaped by key sociodemographic moderators, including gender and education. This suggests that its effects are driven by an interplay of neurobiological mechanisms and divergent adaptive cognitive strategies.