Protein associations and protein–metabolite interactions with depressive symptoms and the p-factor

Despite increasing mental health problems among young people, few studies have examined associations between plasma proteins and mental health. Interactions between proteins and metabolites in association with mental health problems remain underexplored. In 730 twins, we quantified associations between plasma proteins measured at age 22 with 21 indicators of either depressive symptoms or the p-factor and tested for interactions with metabolites. Symptoms were collected from questionnaires and interviews completed by different raters (e.g., self-report, teachers) through adolescence to young adulthood (12 to 22 years). We found 47 proteins associated with depressive symptoms or the p-factor (FDR < 0.2), 9 being associated with both. Two proteins, contactin-1 and mast/stem cell growth factor receptor kit, positively interacted with valine levels in explaining p-factor variability. Our study demonstrates strong associations between plasma proteins and mental health and provides evidence for proteome-metabolome interactions in explaining higher levels of mental health problems.