White matter predictors of worsening of subthreshold hypomania severity in non-bipolar young adults parallel abnormalities in individuals with bipolar disorder

João Paulo Lima Santos; Amelia Versace; Richelle S Stiffler; Haris A Aslam; Jeanette C Lockovich; Lisa Bonar; Michele Bertocci; Satish Iyengar; Genna Bebko; Alexander Skeba; Mary Kay Gill; Kelly Monk; Mary Beth Hickey; Boris Birmaher; Mary L Phillips

doi:10.1016/j.jad.2022.03.039

White matter predictors of worsening of subthreshold hypomania severity in non-bipolar young adults parallel abnormalities in individuals with bipolar disorder

J Affect Disord. 2022 Jun 1:306:148-156. doi: 10.1016/j.jad.2022.03.039. Epub 2022 Mar 21.

Authors

Affiliations

¹ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: santosjp@upmc.edu.
² Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA; Department of Radiology, Magnetic Resonance Research Center, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA.
³ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Background: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals.

Methods: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF).

Results: Lower FA in left CB (middle, β = -0.22, P = 0.022; posterior, β = -0.32, P < 0.001), right CB (anterior, β = -0.30, P = 0.003; posterior, β = -0.27, P = 0.005), and right UF (frontal, β = -0.29, P = 0.002; temporal, β = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals.

Limitations: Relatively short follow-up.

Conclusions: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions.

Keywords: Bipolar disorder; Hypomania; Neural markers; Risk; White matter; dMRI.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anisotropy
Bipolar Disorder* / psychology
Diffusion Tensor Imaging / methods
Humans
Mania
White Matter* / diagnostic imaging
White Matter* / pathology
Young Adult

Abstract

Publication types

MeSH terms

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