Computational modeling of the N-Back task in the ABCD study: associations of drift diffusion model parameters to polygenic scores of mental disorders and cardiometabolic diseases.

BACKGROUND Cognitive dysfunction is common in mental disorders and represents a potential risk factor in childhood. The nature and extent of associations between childhood cognitive function and polygenic risk for mental disorders is unclear. We applied computational modeling to gain insight into mechanistic processes underlying decision making and working memory in childhood and their associations with PRS for mental disorders and comorbid cardiometabolic diseases. METHODS We used the drift diffusion model to infer latent computational processes underlying decision-making and working memory during the N-back task in 3707 children aged 9-10 from the ABCD Study. SNP-based heritability was estimated for cognitive phenotypes, including computational parameters, aggregated N-back task performance and neurocognitive assessments. PRS was calculated for Alzheimer's disease (AD), bipolar disorder, coronary artery disease (CAD), major depressive disorder, obsessive-compulsive disorder, schizophrenia and type 2 diabetes. RESULTS Heritability estimates of cognitive phenotypes ranged from 12 to 38%. Bayesian mixed models revealed that slower accumulation of evidence was associated with higher PRS for CAD and schizophrenia. Longer non-decision time was associated with higher PRS for AD and lower PRS for CAD. Narrower decision threshold was associated with higher PRS for CAD. Load-dependent effects on non-decision time and decision threshold were associated with PRS for AD and CAD, respectively. Aggregated neurocognitive test scores were not associated with PRS for any of the mental or cardiometabolic phenotypes. CONCLUSIONS We identified distinct associations between computational cognitive processes to genetic risk for mental illness and cardiometabolic disease, which could represent childhood cognitive risk factors.