Psychiatric Polygenic Risk Scores and Week-by-Week Symptomatic Status in Youth with Bipolar Disorder: An Exploratory Study

Mar 10, 2025Journal of child and adolescent psychopharmacology

Genetic Risk Scores and Weekly Symptoms in Young People with Bipolar Disorder

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Abstract

246 youth with bipolar disorder (BD) were assessed for mood symptoms over a median of 8.7 years.

Higher polygenic risk scores (PRSs) for BD were significantly associated with a lower most severe lifetime depression score at intake.
Higher PRSs for schizophrenia (SCZ) and major depressive disorder (MDD) were associated with significantly less time spent in a stable mood state (euthymia).
Youth with higher SCZ-PRS experienced more time with any subsyndromal mood symptoms during follow-up.
Youth with higher MDD-PRS also spent more time with any subsyndromal mood symptoms during follow-up.
No significant associations were found between PRSs for BD and attention-deficit/hyperactivity disorder (ADHD) with longitudinal mood variables.

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Prior studies have demonstrated that, in both adults and youth, bipolar disorder (BD) is a polygenic illness. However, no studies have examined polygenic risk scores (PRSs) in relation to the longitudinal course of mood symptoms in youth with BD.This study included 246 youth of European ancestry with BD (7-20 years old at intake) from the Course and Outcome of Bipolar Youth study and Centre for Youth Bipolar Disorder. Mood symptom severity was assessed at intake and, for 168 participants, prospectively for a median of 8.7 years. PRSs for BD, schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were constructed using genome-wide summary statistics from independent adult cohorts.Higher BD-PRS was significantly associated with lower most severe lifetime depression score at intake (= -0.14,= 0.03). Higher SCZ-PRS and MDD-PRS were associated with significantly less time spent in euthymia (SCZ-PRS:= -0.21,= 0.02; MDD-PRS:= -0.22,= 0.01) and more time with any subsyndromal mood symptoms (i.e., any mania, mixed, or depression symptoms; SCZ-PRS:= 0.15,= 0.04; MDD-PRS:= 0.17,= 0.01) during follow-up. PRSs for BD and ADHD were not significantly associated with any longitudinal mood variable.This exploratory analysis was the first to examine psychiatric PRSs in relation to the prospective course of mood symptoms among youth with BD. Results from the current study can serve to guide future youth BD studies with larger sample sizes on this topic. Introduction: Methods: Results: Conclusions: β p β p β p β p β p

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Psychiatric Polygenic Risk Scores and Week-by-Week Symptomatic Status in Youth with Bipolar Disorder: An Exploratory Study

Abstract

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