Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia

Fernando Caravaggio, Margaret Hahn, Shinichiro Nakajima, Philip Gerretsen, Gary Remington, Ariel Graff-Guerrero

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Schizophrenia is a severe and chronic neuropsychiatric disorder which affects 1% of the world population. Using the brain imaging technique positron emission tomography (PET) it has been demonstrated that persons with schizophrenia have greater dopamine transmission in the striatum compared to healthy controls. However, little progress has been made as to elucidating other biological mechanisms which may account for this hyperdopaminergic state in this disease. Studies in animals have demonstrated that insulin receptors are expressed on midbrain dopamine neurons, and that insulin from the periphery acts on these receptors to modify dopamine transmission in the striatum. This is pertinent given that several lines of evidence suggest that insulin receptor functioning may be abnormal in the brains of persons with schizophrenia. Post-mortem studies have shown that persons with schizophrenia have less than half the number of cortical insulin receptors compared to healthy persons. Moreover, these post-mortem findings are unlikely due to the effects of antipsychotic treatment; studies in cell lines and animals suggest antipsychotics enhance insulin receptor functioning. Further, hyperinsulinemia - even prior to antipsychotic use - seems to be related to less psychotic symptoms in patients with schizophrenia. Collectively, these data suggest that midbrain insulin receptor functioning may be abnormal in persons with schizophrenia, resulting in reduced insulin-mediated regulation of dopamine transmission in the striatum. Such a deficit may account for the hyperdopaminergic state observed in these patients and would help guide the development of novel treatment strategies. We hypothesize that, (i) insulin receptor expression and/or function is reduced in midbrain dopamine neurons in persons with schizophrenia, (ii) basal insulin should reduce dopaminergic transmission in the striatum via these receptors, and (iii) this modulation of dopaminergic transmission by basal insulin is reduced in the brains of persons with schizophrenia.

Original languageEnglish
Pages (from-to)391-396
Number of pages6
JournalMedical Hypotheses
Volume85
Issue number4
DOIs
Publication statusPublished - 2015 Oct 1
Externally publishedYes

Fingerprint

Corpus Striatum
Insulin Receptor
Dopamine
Schizophrenia
Insulin
Mesencephalon
Antipsychotic Agents
Dopaminergic Neurons
Brain
Hyperinsulinism
Neuroimaging
Positron-Emission Tomography
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia. / Caravaggio, Fernando; Hahn, Margaret; Nakajima, Shinichiro; Gerretsen, Philip; Remington, Gary; Graff-Guerrero, Ariel.

In: Medical Hypotheses, Vol. 85, No. 4, 01.10.2015, p. 391-396.

Research output: Contribution to journalArticle

Caravaggio, Fernando ; Hahn, Margaret ; Nakajima, Shinichiro ; Gerretsen, Philip ; Remington, Gary ; Graff-Guerrero, Ariel. / Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia. In: Medical Hypotheses. 2015 ; Vol. 85, No. 4. pp. 391-396.
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