Illness duration and total brain gray matter in bipolar disorder: Evidence for neurodegeneration?
Abstract
Previous studies have suggested that bipolar disorder (BD) is associated with alterations in neuronal plasticity, but the effects of the progression of illness on brain anatomy have been poorly investigated. We studied the correlation between length of illness, age, age at onset, and the number of previous episodes and total brain, total gray, and total white matter volumes in BD, unipolar (UP) and healthy control (HC) subjects. Thirty-six BD, 31 UP and 55 HCs underwent a 1.5 T brain magnetic resonance imaging scan, and gray and white matter volumes were manually traced blinded to the subjects' diagnosis. Partial correlation analysis showed that length of illness was inversely correlated with total gray matter volume after adjusting for total intracranial volume in BD (r(p)= -0.51; p=0.003) but not in UP subjects (r(p)= -0.23; p=0.21). Age at illness onset and the number of previous episodes were not significantly correlated with gray matter volumes in BD or UP subjects. No significant correlation with total white matter volume was observed. These results suggest that the progression of illness may be associated with abnormal cellular plasticity. Prospective longitudinal studies are necessary to elucidate the long-term effects of illness progression on brain structure in major mood disorders.
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BDNF, oxidative stress, and inflammation tend to be abnormal among individuals with multiple mood episodes and correlate with length of illness.
“there is also evidence suggesting that BDNF, oxidative stress, and inflammation tend to be abnormal among individuals with multiple mood episodes and correlate with length of illness [51, 66, 67].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [66]
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- Authors
- Frey, B. N., Zunta-Soares, G. B., Caetano, S. C., Nicoletti, M. A., Hatch, J. P., Brambilla, P., Mallinger, A. G., & Soares, J. C.
- Affiliations
- McMaster University (CA)
- Universidade de São Paulo (BR)
- University of North Carolina at Chapel Hill (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of Pittsburgh (US)
- Corresponding author
- Soares, Jair C.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 18
- Issue
- 10
- Pages
- 717-722
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2091318875
- Cited by
- 79
- References
- 38
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 5 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 4
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH069774, R01MH068766, MH 68766, MH-69774)
- National Center for Research Resources (K24RR020571, RR20571)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, length of illness, gray matter volume, white matter volume, neurodegeneration, major depressive disorder, age of onset, number of episodes, brain structure, neuroplasticity, major mood disorders
- MeSH terms
- Adolescent, Adult, Bipolar Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Degeneration, Statistics as Topic, Disease Progression
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