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.
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Enhanced insulin signaling with antidiabetic treatments, such as thiazolidinediones, may preserve and/or augment cognitive function at least in a subset of major depressive disorder patients exhibiting comorbid metabolic conditions.
“In keeping with the view outlined above, enhanced insulin signaling with antidiabetic treatments, for example, thiazolidinediones such as rosiglitazone and pioglitazone, may preserve and/or augment cognitive function at least in a subset of MDD patients exhibiting comorbid metabolic conditions [115].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [115]
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Self-citation
- Authors
- McIntyre, R. S., Soczynska, J. K., Woldeyohannes, H. O., Lewis, G. F., Leiter, L. A., MacQueen, G. M., Miranda, A., Fulgosi, D., Konarski, J. Z., & Kennedy, S. H.
- Affiliations
- University Health Network (CA)
- Mount Sinai Hospital (CA)
- St. Michael's Hospital (CA)
- McMaster University (CA)
- ORCID
- Venue
- Expert Opinion on Pharmacotherapy
- Publisher
- Informa UK Limited
- Published
- 2007-08
- Volume
- 8
- Issue
- 11
- Pages
- 1615-1628
- ISSN
- 1465-6566 (ISSN-L)
- 1744-7666
- OpenAlex
- W2135344776
- Cited by
- 32
- References
- 129
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- AstraZeneca
- GlaxoSmithKline
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- thiazolidinediones, rosiglitazone, pioglitazone, mood disorders, cognitive impairment, major depressive disorder, bipolar disorder, Alzheimer's disease, peroxisome proliferator-activated receptors, neuroprotection, insulin signaling, anti-inflammatory activity, glucocorticoid activity, oxidative stress, neuroplasticity, excitotoxicity
- MeSH terms
- Animals, Cognition Disorders, Humans, Mood Disorders, Thiazolidinediones
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