Managing psychiatric disorders with antidiabetic agents: translational research and treatment opportunities.
The objective of this paper is to synthesise extant studies describing the neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders. The authors conducted a MedLine search of all English-language articles published between 1966 and March 2006. The search terms were the nonproprietary names of established and putative antidiabetic agents (e.g., insulin, insulin secretagogues and sensitisers) cross-referenced with the individual names of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined mood, psychotic, anxiety and dementing disorders. The search was augmented with a manual review of article reference lists. Contemporary models of disease pathophysiology in major depressive disorder, bipolar disorder and several dementing disorders (e.g., Alzheimer's disease) emphasise alterations in cellular plasticity and cytoarchitecture, with associated regional abnormalities in neuronal and glial density and morphology. Antidiabetic treatments (e.g., thiazolidinediones) may be capable of attenuating this pathological process via disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory). Enhanced insulin signalling with antidiabetic treatments may preserve and/or augment cognitive function in several neuropsychiatric disorders. Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders.
McIntyre
Roger S
RS
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street-Toronto, ON, M5T 2S8, Canada. roger.mcintyre@uhn.on.ca
Soczynska
Joanna K
JK
Lewis
Gary F
GF
MacQueen
Glenda M
GM
Konarski
Jakub Z
JZ
Kennedy
Sidney H
SH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003071:Cognition; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010848:Picolinic Acids / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D007328:Insulin; D010848:Picolinic Acids; D045162:Thiazolidinediones; D008063:Thioctic Acid; C030614:picolinic acid