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Review
. 2014 Sep:56:18-27.
doi: 10.1016/j.jpsychires.2014.04.017. Epub 2014 May 2.

Inflammatory mediators of cognitive impairment in bipolar disorder

Isabelle E Bauer  1 , Michaela C Pascoe  2 , Bianca Wollenhaupt-Aguiar  3 , Flavio Kapczinski  4 , Jair C Soares  5
Affiliations
Review

Inflammatory mediators of cognitive impairment in bipolar disorder

Isabelle E Bauer et al. J Psychiatr Res. 2014 Sep.

Abstract

Objectives: Recent studies have pointed to neuroinflammation, oxidative stress and neurotrophic factors as key mediators in the pathophysiology of mood disorders. Little is however known about the cascade of biological episodes underlying the cognitive deficits observed during the acute and euthymic phases of bipolar disorder (BD). The aim of this review is to assess the potential association between cognitive impairment and biomarkers of inflammation, oxidative stress and neurotrophic activity in BD.

Methods: Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to November 2013, for human studies that collected both inflammatory markers and cognitive data in BD. Selected search terms were bipolar disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic.

Results: Ten human studies satisfied the criteria for consideration. The findings showed that high levels of peripheral inflammatory-cytokine, oxidative stress and reduced brain derived neurotrophic factor (BDNF) levels were associated with poor cognitive performance. The BDNF val66met polymorphism is a potential vulnerability factor for cognitive impairment in BD.

Conclusions: Current data provide preliminary evidence of a link between the cognitive decline observed in BD and mechanisms of neuroinflammation and neuroprotection. The identification of BD specific inflammatory markers and polymorphisms in inflammatory response genes may be of assistance for therapeutic intervention.

Keywords: Bipolar disorder; Cognitive functioning; Neuroinflammation; Neurotrophin; Oxidative stress.

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Conflict of interest statement

Declaration of interest

Dr Bauer, Dr Pascoe and Dr Wollenhaupt-Aguiar have no conflicts of interest

Professor Kapczinski has received grants/research support from Astra-Zeneca, Eli Lilly, Janssen-Cilag, Servier, CNPq, CAPES, NARSAD and Stanley Medical Research Institute; has been a member of the board of speakers for Astra-Zeneca, Eli Lilly, Janssen and Servier; and has served as a consultant for Servier.

Professor J. C. Soares has received grants/research support from Forrest, BMS, Merck, Stanley Medical Research Institute, NIH and has been a speaker for Pfizer and Abbott.

Figures

Figure 1
Figure 1
Bipolar disorders are characterized by elevated levels of peripheral pro-inflammatory cytokines such as interleukins (IL-6, IL-2R, IL-1beta), tumour necrosis factor (TNF-α) and oxidative stress (Thiobarbituric acid reactive substances -TBARS and C-reactive protein - CRP). Pro-inflammatory agents enter the central nervous system (CNS) via the blood brain barrier, activate the brain inflammatory signal and release inflammatory agents, monocytes and macrophages in the brain. Exposure to pro-inflammatory substances and reactive oxidative substances is associated with neuronal damage and loss of brain function.
Figure 2
Figure 2
PRISMA flowchart (38) showing the filtering process used to select the 10 studies included in the systematic review of studies investigating inflammatory markers and cognition in bipolar disorder
See this image and copyright information in PMC

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