Childhood maltreatment and cognitive functioning: the role of depression, parental education, and polygenic predisposition

Childhood maltreatment (CM) is a significant vulnerability factor for various psychiatric disorders, including major depressive disorder (MDD). Research suggests that CM leads to long-term adverse biological effects, particularly in limbic and prefrontal areas, resulting in cognitive deficits. However, previous studies have yielded inconsistent results regarding the specific cognitive domains affected by CM and have often failed to adequately control for confounders like depression, socioeconomic status (SES), and genetic predisposition. This study aimed to isolate the relationship between CM and cognitive dysfunction across multiple domains while controlling for these confounders and investigating gene-environment interactions. The researchers hypothesized that CM, MDD diagnosis, and genetic predisposition for MDD would be negatively associated with cognitive abilities, while higher parental education (PE) and genetic predisposition for educational attainment would be positively associated. They also tested the hypothesis that CM has an independent effect on cognition even after controlling for other factors.

Existing literature shows a link between CM and cognitive deficits, but findings are inconsistent across cognitive domains. Some studies report widespread cognitive deficits in individuals with CM, while others find more specific effects on attention and memory. Most studies, however, lack adequate control for psychiatric diagnoses and SES. SES, often proxied by parental education, is associated with both CM and cognitive functioning, potentially confounding the CM-cognition relationship. Genetic factors also play a role, with shared genetic influences on SES and cognition. The potential mediating role of MDD in the CM-cognition association is unclear, as is the interplay between genetic predisposition and CM's impact on cognition. This research aimed to address these gaps by examining the individual and combined influence of MDD diagnosis, PE, and genetic variables on the CM-cognition relationship, while also exploring potential interactions.

The study used data from the Marburg–Münster Affective Disorders Cohort Study (MACS), including 547 individuals with MDD and 670 healthy controls (N=1217; mean age 34.7 years; 62.64% female). CM was assessed using the Childhood Trauma Questionnaire (CTQ), PE served as a proxy for SES, and current and lifetime psychiatric diagnoses were assessed using the Structured Clinical Interview for DSM-IV (SCID-I). Cognitive functioning was evaluated using a neuropsychological test battery covering working memory, executive functioning, processing speed, attention, memory, and verbal intelligence. Polygenic scores (PGS) for depression and educational attainment were calculated. Multivariate analyses of cognitive domains were conducted to examine the associations with CM, PE, and PGS, both individually and concurrently. Interaction effects between CM and other variables were also explored. Statistical methods employed included multivariate analysis of variance (MANOVA), and regression analyses.

Multivariate analysis revealed significant associations between cognitive functioning and CM (η² = 0.083, P < 0.001), parental education (η² = 0.085, P < 0.001), and polygenic scores for depression (η² = 0.021, P = 0.005) and educational attainment (η² = 0.031, P < 0.001). These associations remained significant even when all predictors were included in a single model. Univariate analyses indicated that CM was associated with poorer performance across all cognitive domains. Including MDD diagnosis and PE in the models showed that these variables explained a substantial portion of the CM-cognition association. The inclusion of PGS for MDD and educational attainment did not significantly alter the CM-cognition association. However, the PGS were independently associated with cognitive performance: the MDD PGS was associated with lower visuospatial working memory, while the EdA PGS was positively associated with several cognitive measures. Interactions between CM and sex, and CM and age, were also observed, suggesting potential moderating roles of these factors.

The findings demonstrate that CM, MDD diagnosis, and PE are independently associated with cognitive functioning, even when controlling for each other. CM was consistently linked to poorer cognitive performance across multiple domains, although a substantial portion of this association was explained by MDD diagnosis and PE. The results corroborate previous research showing the detrimental impact of CM on cognition but emphasize the importance of controlling for MDD and SES. The study also provides evidence for the independent contribution of genetic predisposition to cognitive abilities, suggesting that both environmental and genetic factors contribute to the observed relationships. The lack of significant interaction effects between CM and other factors implies that the association between CM and cognitive ability was relatively consistent across different diagnostic and SES groups.

This study provides compelling evidence for the independent and combined effects of CM, MDD, parental education, and genetic predispositions on cognitive function. The findings highlight the need for comprehensive interventions that address these multiple interacting factors to improve cognitive outcomes in individuals with a history of CM. Future research should investigate longitudinal relationships between these variables to better understand the causal pathways and develop targeted interventions. Further research is also needed to explore the clinical significance of the observed effects, and the mechanisms through which CM affects cognition.

The cross-sectional nature of the study limits causal inferences. Retrospective self-report measures of CM may be susceptible to bias. The use of PE as a proxy for SES might not fully capture the complexity of socioeconomic factors. The specific PGS used might not encompass the full range of genetic influences on cognition and depression.