Differentiating white matter measures that protect against vs. predispose to bipolar disorder and other psychopathology in at-risk youth

Renata Rozovsky,Lisa K Bonar,Amelia Versace,Tina Goldstein,Boris Birmaher,Michele Bertocci,Cecile D Ladouceur,Halimah Abdul-Waalee,Jay Fournier,Mary L Phillips,Danella Hafeman,Dara Sakolsky,Kelly Monk,Genna Bebko

doi:10.1038/s41386-021-01088-1

Abstract

Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q < 0.05); and in bilateral ATR (posterior portion) versus at-risk groups (q < 0.001). Healthy, but not non-BD, at-risk participants showed significantly higher FA in bilateral ATR clusters than healthy controls (qs < 0.05). At-risk groups showed higher FA in these clusters than BD participants (qs < 0.05). Non-BD versus healthy at-risk participants, and Converters versus offspring of BD parents, showed lower FA in the right ATR cluster (qs < 0.05). Low anterior right CB FA in BD participants versus other groups might result from having BD. High bilateral ATR FA in at-risk groups, and in healthy at-risk participants, versus healthy controls might protect against BD/other psychiatric disorders. Absence of elevated right ATR FA in non-BD versus healthy at-risk participants, and in Converters versus non-converter offspring of BD parents, might lower protection against BD in at-risk groups.

Highlights

Bipolar Disorder (BD) is one of the most debilitating psychiatric illnesses, affecting 1–3% of the adult population worldwide
BD commonly occurs in adolescence or early adulthood, and causes emotional and behavioral problems often leading to poor psychosocial function, substance abuse and suicide [1,2,3]
The longitudinal Bipolar Offspring Study (BIOS) [10], which examines the development of psychiatric symptomatology in offspring of Bipolar parents (OBP), and other studies reported rates of BD in OBP ranging from 15 to 20% [11,12,13]

Summary

Introduction

Bipolar Disorder (BD) is one of the most debilitating psychiatric illnesses, affecting 1–3% of the adult population worldwide. Earlier identification of future BD risk is a key research priority in BD [9]. The longitudinal Bipolar Offspring Study (BIOS) [10], which examines the development of psychiatric symptomatology in offspring of Bipolar parents (OBP), and other studies reported rates of BD in OBP ranging from 15 to 20% [11,12,13]. In offspring of parents with early-onset BD, the risk increases to 30–50% [5, 14, 15]. Pediatric populations, and especially OBP, are appropriate populations in which to examine factors associated with future BD risk

Methods

Results

Conclusion