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The role of hippocampus in the pathophysiology of bipolar disorder

Frey, Benicio N.a e; Andreazza, Ana C.a b; Nery, Fabiano G.c f g; Martins, Marcio R.d; Quevedo, Joãod; Soares, Jair C.h; Kapczinski, Flávioa

doi: 10.1097/FBP.0b013e3282df3cde

Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD.

aBipolar Disorders Program and Laboratory of Molecular Psychiatry, Hospital de Clinicas de Porto Alegre

bDepartment of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul

cDepartment of Psychiatry, Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo

dLaboratory of Neuroscience, Programa de Pós-Graduação em Ciências da Saúde, University do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil

eMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

Department of fPsychiatry, The University of Texas Health Science Center at San Antonio

gPsychiatry Service, South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas

hCenter of Excellence for Research and Treatment of Bipolar Disorder, Department of Psychiatry, UNC School of Medicine, Chapel Hill, North Carolina, USA

Correspondence to Dr Benicio N. Frey, MD, PhD, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada


Received 30 March 2007 Accepted as revised 29 May 2007

© 2007 Lippincott Williams & Wilkins, Inc.