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.

ABSTRACT

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 polygenic risk scores (PRSs) 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 ages 9 to 10 years from the Adolescent Brain Cognitive Development (ABCD) Study. Single nucleotide polymorphism-based heritability was estimated for cognitive phenotypes, including computational parameters, aggregated n-back task performance, and neurocognitive assessments. PRSs were calculated for Alzheimer's disease, 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 PRSs for CAD and schizophrenia. Longer nondecision time was associated with higher PRSs for Alzheimer's disease and lower PRSs for CAD. Narrower decision threshold was associated with higher PRSs for CAD. Load-dependent effects on nondecision time and decision threshold were associated with PRSs for Alzheimer's disease and CAD, respectively. Aggregated neurocognitive test scores were not associated with PRSs for any of the mental or cardiometabolic phenotypes. CONCLUSIONS: We identified distinct associations between computational cognitive processes and genetic risk for mental illness and cardiometabolic disease, which could represent childhood cognitive risk factors.