Thiazolidinediones: novel treatments for cognitive deficits in mood disorders?

Abstract

The aim of this review is to provide a rationale for evaluating thiazolidinediones (TZDs) as putative treatments for cognitive deficits in individuals with mood disorders. A MedLine search of all English-language articles published between January 1966 and August 2006 was conducted. The search terms were: the non-proprietary names of TZDs (e.g., rosiglitazone and pioglitazone), peroxisome proliferator-activated receptor, cognition, neuroprotection, inflammation, oxidative stress, cellular metabolism and excitotoxicity cross-referenced with the individual names of mood (e.g., major depressive disorder and bipolar disorder) and dementing disorders (e.g., Alzheimer's disease) as defined in the Diagnostic and Statistical Manual of Mental Disorders third edition, revised/fourth edition, text revision (DSM-III-R/IV-TR). The search was augmented with a manual review of article reference lists. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures and overall manuscript quality. Contemporary pathophysiologic models of mood disorders emphasize alterations in neuronal plasticity, metabolism and cytoarchitecture with associated regional abnormalities in neuronal (and glial) density and morphology. These abnormalities are hypothesized to subserve cognitive deficits and other clinical features of mood disorders. TZDs may attenuate, abrogate and/or reverse the neurotoxic effects of depressive illness by means of disparate mechanisms, notably insulin signaling, anti-inflammation, glucocorticoid activity and cellular metabolism. Extant data provide the basis for formulating a hypothesis that TZDs may be salutary for cognitive deficits and several aspects of somatic health (e.g., cardiovascular disease) associated with mood disorders.

Keywords::

• bipolar disorder
• cognition
• dementia
• depression
• diabetes
• glucose homeostasis
• insulin
• thiazolidinedione

Acknowledgements

RS McIntyre is a consultant and speaker for: Astra-Zeneca, Biovail, Bristol Meyers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Organon, Oryx, Pfizer, Prestwick, Shire and Wyeth. He has also received research funding from Astra-Zeneca, GlaxoSmithKline, Merck, Servier and Wyeth. LA Leiter has received research funding from GlaxoSmithKline, has provided continuing medical education on behalf of Eli Lilly and GlaxoSmithKline, and has acted as a consultant for Eli Lilly and GlaxoSmithKline. SH Kennedy is a consultant and speaker for AstraZeneca, Biovail, Eli Lilly, Janssen-Ortho, Lundbeck, Novartis, Pfizer, Servier and Wyeth. He has received research funding from Advanced Neuromodulatory Systems, AstraZeneca, Eli Lilly, GlaxoSmithKline and Lundbeck.

The authors would like to thank Dragana Vagic for her comments on the manuscript.

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