Cerebro-cerebellar white matter connectivity in bipolar disorder and associated polarity subphenotypes

Georgios D Argyropoulos; Foteini Christidi; Efstratios Karavasilis; Georgios Velonakis; Anastasia Antoniou; Peter Bede; Ioannis Seimenis; Nikolaos Kelekis; Athanasios Douzenis; Olympia Papakonstantinou; Efstathios Efstathopoulos; Panagiotis Ferentinos

doi:10.1016/j.pnpbp.2020.110034

Cerebro-cerebellar white matter connectivity in bipolar disorder and associated polarity subphenotypes

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10:104:110034. doi: 10.1016/j.pnpbp.2020.110034. Epub 2020 Jul 22.

Affiliations

¹ Research Unit of Radiology and Medical Imaging, 2nd Department of Radiology, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² 2nd Department of Psychiatry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: christidi.f.a@gmail.com.
³ 2nd Department of Psychiatry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴ Biomedical Imaging Laboratory, Sorbonne University, CNRS, INSERM, Paris, France; Computational Neuroimaging Group, Trinity College Dublin, Ireland.
⁵ Medical Physics Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

PMID: 32710925
DOI: 10.1016/j.pnpbp.2020.110034

Abstract

Background: The cerebellum has a crucial role in mood regulation. While cerebellar grey matter (GM) alterations have been previously reported in bipolar disorder (BD), cerebro-cerebellar white matter (WM) connectivity alterations and cerebellar GM profiles have not been characterised in the context of predominant polarity (PP) and onset polarity (OP) subphenotypes of BD patients which is the aim of the present study.

Methods: Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this quantitative neuroimaging study to evaluate cerebellar GM patterns and cerebro-cerebellar WM connections. Diffusion tensor tractography was used to characterise afferent and efferent cerebro-cerebellar tract integrity. False discovery rate corrections were applied in post-hoc comparisons.

Results: BD patients exhibited higher fractional anisotropy (FA) in fronto-ponto-cerebellar tracts bilaterally compared to HC. Subphenotype-specific FA profiles were identified within the BD cohort. Regarding PP subgroups, we found FA changes in a) left contralateral fronto-ponto-cerebellar tract (depressive-PP > HC) and b) contralateral/ipsilateral fronto-ponto-cerebellar tracts bilaterally (manic-PP > HC). Regarding OP subgroups, we observed FA changes in a) left/right contralateral fronto-ponto-cerebellar tracts (depressive-OP > HC) and b) all fronto-ponto-cerebellar, most parieto-ponto-cerebellar and right contralateral occipito-ponto-cerebellar tracts (manic-OP>HC). In general, greater and more widespread cerebro-cerebellar changes were observed in manic-OP patients than in depressive-OP patients compared to HC. Manic-OP showed higher FA compared to depressive-OP patients in several afferent WM tracts. No GM differences were identified between BD and HC and across BD subgroups.

Conclusions: Our findings highlight fronto-ponto-cerebellar connectivity alterations in euthymic BD. Polarity-related subphenotypes have distinctive cerebro-cerebellar WM signatures with potential clinical and pathobiological implications.

Keywords: Bipolar disorder; Cerebellum; Euthymia; Onset polarity; Predominant polarity; Tractography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Bipolar Disorder / diagnostic imaging*
Bipolar Disorder / psychology
Cerebellum / diagnostic imaging*
Cerebrum / diagnostic imaging
Cross-Sectional Studies
Diffusion Tensor Imaging / methods
Female
Frontal Lobe / diagnostic imaging*
Humans
Male
Middle Aged
Nerve Net / diagnostic imaging*