Cerebro-cerebellar white matter connectivity in bipolar disorder and associated polarity subphenotypes
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.
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Individuals with BD who experienced predominant manic episodes showed more extensive cerebro-cerebellar changes than those who had predominant depressive episodes compared to HC.
“Individuals with BD who experienced predominant manic episodes showed more extensive cerebro-cerebellar changes than those who had predominant depressive episodes compared to HC (Argyropoulos et al., 2021).”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Argyropoulos et al., 2021
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Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review.
Qela, B., Damiani, S., De Santis, S., Groppi, F., Pichiecchio, A., Asteggiano, C., Brondino, N., Monteleone, A. M., Grassi, L., Politi, P., et al. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106020 · Cited by 26 · see citing works
“Individuals with BD who experienced predominant manic episodes showed more extensive cerebro-cerebellar changes than those who had predominant depressive episodes compared to HC (Argyropoulos et al., 2021).”
- Authors
- Argyropoulos, G. D., Christidi, F., Karavasilis, E., Velonakis, G., Antoniou, A., Bede, P., Seimenis, I., Kelekis, N., Douzenis, A., Papakonstantinou, O., Efstathopoulos, E., & Ferentinos, P.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Christidi, Foteini
- ORCID
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 104
- Pages
- 110034
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W3045133532
- Cited by
- 24
- References
- 114
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 4
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Social Fund-ESF (5033021)
- National Strategic Reference Framework (NSRF 2014-2020)
- the Health Research Board (HRB EIA-2017-019)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, predominant polarity, fractional anisotropy, cerebellar white matter, cerebellar gray matter, mood regulation, euthymic bipolar patients
- MeSH terms
- Adult, Bipolar Disorder, Cerebellum, Cross-Sectional Studies, Female, Frontal Lobe, Humans, Male, Middle Aged, Nerve Net, Cerebrum, Diffusion Tensor Imaging
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