Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults.

Silvia Biere,Michael Bauer,Andrea Pfennig,Andreas G Chiocchetti,Aliaksandr Malyshau,Murielle Brum,Kristiyana Petrova,Andreas Reif,Oliver Grimm,Fabian Streit,Thorsten M Kranz,Silke Matura,Viola Oertel,Thomas G Schulze,Natalie Brunkhorst-Kanaan,Sarah Kittel-Schneider

doi:10.3389/fpsyt.2020.552532

Abstract

Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.

Highlights

Bipolar disorder (BD), which is characterized by recurrent episodes of mania and depression, is a severe and often chronic mental disorder associated with increased premature mortality and disability and reduced quality of life [1, 2]
A major strength of our study is that we focus on young adults, since numerous prior studies have shown that early age of onset for MDD is a predictor of bipolar conversion [24]
In view of the fact that we focused on young adults in our study, our findings might represent a distinct early-onset subtype of BD

Summary

Introduction

Bipolar disorder (BD), which is characterized by recurrent episodes of mania and depression, is a severe and often chronic mental disorder associated with increased premature mortality and disability and reduced quality of life [1, 2]. The first symptoms of the disorder occur many years before patients meet full diagnostic criteria, typically in adolescence, which marks a high-risk period for BD onset [3, 4]. In the early course of BD, mood and drive are often dysregulated [9], which manifests in episodes of (subclinical) depression as well as (sub)threshold hypomania—these increase in severity and frequency during the period until onset [4, 6, 10]. Additional symptoms include sleep disturbances, fear, anger, and irritability, which often occur in the early course and become more specific and similar to BD symptoms over time [4, 8, 9, 12]

Methods

Results

Conclusion