12.2 CAN POLYGENIC RISK SCORES HELP IDENTIFY PEDIATRIC BIPOLAR SPECTRUM AND RELATED DISORDERS? A SYSTEMATIC LITERATURE REVIEW

Abstract

Because the genetic basis of complex disorders such as mood disorders is polygenic, clinically relevant information could emerge from genetic markers in aggregate in the form of polygenic risk scores. In this study, we aimed to examine the available body of knowledge on the association between polygenic risk scores for bipolar disorder polygenic risk score (BP-PRS) and pediatric bipolar spectrum and related disorders. We performed a literature search through PubMed in March of 2020 utilizing the following search algorithms: 1) [polygenic risk or polygenic] AND [bipolar disorder or bipolar or bipolar depression]; or 2) [polygenic risk or polygenic] AND [depression or MDD or MD]; or 3) [polygenic risk or polygenic] AND [attention or ADHD or conduct disorder symptoms or emotional dysregulation or aggression]. All articles were screened for predetermined inclusion/exclusion criteria. BP-PRSs were significantly associated with deficits in executive functioning, the diagnosis of ADHD, and associated executive-function deficits. Only one study included in our analysis directly compared MDD-PRSs to BP-PRSs in youth. Results showed that in a population sample of more than 40,000 children aged 6 to 17 years, only MDD-PRSs and not BP-PRSs were associated with ADHD symptoms, internalizing problems, and social problems. ADHD-PRSs were associated with conduct problems, depressive symptomatology, and externalizing disorders symptoms. Findings revealed that while higher BP-PRSs were correlated with increased hypomania scores, ADHD-PRSs were more clearly associated with emotional reactivity, emotional dysregulation, and irritability—frequent correlates of pediatric bipolar spectrum disorder. Although MDD-PRSs were predictive of more severe pediatric MDD trajectories, their contribution to the development of pediatric BP spectrum and related disorders remains unknown because the available studies did not examine the risk for bipolar (BP) and BP spectrum disorder. Taken together, these findings suggest that ADHD-PRSs may have the most important contribution to the development of mood-related problems in youth and may begin to explain the high comorbidity between ADHD with mood and emotional dysregulation problems in the young.