title: Challenges and developments in research of the early stages of bipolar disorder.
abstract: Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.
authors.affiliation: Grupo de Pesquisa em Neurociência Comportamental e Molecular do Transtorno Bipolar, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LINC), UNIFESP, São Paulo, SP, Brazil.|Programa de Intervenção em Estados Mentais de Risco (PRISMA), Departamento de Psiquiatria, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia - Medicina Translacional (INCT-TM), Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Medicina, Departamento de Psiquiatria, UFRGS, Porto Alegre, RS, Brazil.|Departamento de Farmacologia, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Adriane R
authors.initials: AR
authors.lastname: Rosa
authors.affiliation: Grupo de Pesquisa em Neurociência Comportamental e Molecular do Transtorno Bipolar, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LINC), UNIFESP, São Paulo, SP, Brazil.|Programa de Intervenção em Estados Mentais de Risco (PRISMA), Departamento de Psiquiatria, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Pedrini
authors.affiliation: Grupo de Pesquisa em Neurociência Comportamental e Molecular do Transtorno Bipolar, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LINC), UNIFESP, São Paulo, SP, Brazil.|Programa de Intervenção em Estados Mentais de Risco (PRISMA), Departamento de Psiquiatria, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Mariane N
authors.initials: MN
authors.lastname: Noto
authors.affiliation: Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia - Medicina Translacional (INCT-TM), Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Medicina, Departamento de Psiquiatria, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: Academic Psychiatry, Institute of Neuroscience, Newcastle University, UK.|Centre for Affective Disorders, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Scott
mesh_terms: D015415:Biomarkers; D035843:Biomedical Research; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000000981:diagnostic imaging; D003072:Cognition Disorders / Q000175:diagnosis; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers