Cited by 183Bipolar Disorder and TreatmentTreatment of Major DepressionSchizophrenia research and treatment

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The theory of bipolar disorder as an illness of accelerated aging: Implications for clinical care and research

Rizzo, Lucas Bortolotto, Costa, Leonardo Gazzi, Mansur, Rodrigo B., Swardfager, Walter, Belangero, Síntia Iole, Grassi-Oliveira, Rodrigo, McIntyre, Roger S., Bauer, Moisés E., Brietzke, Elisa·2014·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2014.02.004

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Abstract

Bipolar Disorder (BD) has been conceptualized as both a cyclic and a progressive disorder. Mechanisms involved in neuroprogression in BD remain largely unknown although several non-mutually exclusive models have been proposed as explanatory frameworks. In the present paper, we propose that the pathophysiological changes observed in BD (e.g. brain structural alterations, cognitive deficits, oxidative stress imbalance, amyloid metabolism, immunological deregulation, immunosenescence, neurotrophic deficiencies and telomere shortening) converge on a model of accelerated aging (AA). Aging can be understood as a multidimensional process involving physical, neuropsychological, and social changes, which can be highly variable between individuals. Determinants of successful aging (e.g environmental and genetic factors), may also confer differential vulnerability to components of BD pathophysiology and contribute to the clinical presentation of BD. Herein we discuss how the understanding of aging and senescence can contribute to the search for new and promising molecular targets to explain and ameliorate neuroprogression in BD. We also present the strengths and limitations of this concept.

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Miola, A., Medina‐Inojosa, B. J., Barboza, A. B. C., Prieto, M. L., Morgan, R. J., Coombes, B. J., Veldić, M., Ozerdem, A., Singh, B., Gardea‐Resendez, M., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121968
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Barnes-Scheufler, C. V., Yalçın, M., Rösler, L., Schiweck, C., Shing, Y. L., Qubad, M., Reif, A., & Bittner, R. A. (2026) · Research Square · doi:10.21203/rs.3.rs-9514584/v1
Pharmacological maintenance treatment in older age bipolar disorder
Zittema, D., & Dols, A. (2026) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000001101
Regional microstructural changes of the corpus callosum in bipolar disorder: A diffusion MRI tractography study with an exploratory brain-age analysis
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Authors: Rizzo, L. B., Costa, L. G., Mansur, R. B., Swardfager, W., Belangero, S. I., Grassi-Oliveira, R., McIntyre, R. S., Bauer, M. E., & Brietzke, E.
Affiliations: Universidade Federal de São Paulo (BR)
University Health Network (CA)
University of Toronto (CA)
Pontifícia Universidade Católica do Rio Grande do Sul (BR)
Corresponding author: Brietzke, Elisa
ORCID: Rizzo, Lucas Bortolotto
Mansur, Rodrigo B.
Swardfager, Walter
McIntyre, Roger S.
Bauer, Moisés E.
Brietzke, Elisa
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2014-05
Volume: 42
Pages: 157-169
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2014.02.004
OpenAlex: W2031122384
Cited by: 183
References: 228
Citations by year: 2026: 9 · 2025: 11 · 2024: 14 · 2023: 12 · 2022: 22 · 2021: 6 · 2020: 23 · 2019: 16 · 2018: 14 · 2017: 15 · 2016: 17 · 2015: 18 · 2014: 5
FWCI: 2.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
Funders: Toronto Rehabilitation Institute
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: bipolar disorder, accelerated aging, neuroprogression, immunosenescence, telomere shortening, oxidative stress, amyloid metabolism, brain structural changes, cognitive impairment, successful aging, molecular targets
MeSH terms: Animals, Bipolar Disorder, Brain, Humans, Models, Neurological, Aging, Premature

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The theory of bipolar disorder as an illness of accelerated aging: Implications for clinical care and research

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