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

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. (c) 2014 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniv Hlth Network, Mood Disorders Psychopharmacol Unit, Toronto, ON, CanadaUniv Toronto, Sunnybrook Res Inst, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilPontificia Univ Catolica Rio Grande do Sul, Inst Biomed Res, Porto Alegre, RS, BrazilPontificia Univ Catolica Rio Grande do Sul, Fac Biosci, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, São Paulo, BrazilWeb of ScienceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Heart & Stroke Foundation Centre for Stroke RecoveryToronto Rehabilitation Institut