MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Parsey, 2006 PubMed
Full Info	Parsey, R.V., Oquendo, M.A., Ogden, R.T., Olvet, D.M., Simpson, N., Huang, Y.Y., Van Heertum, R.L., Arango, V. and Mann, J.J. (2006) Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry, 59, 106-113.

Study

Hypothesis or Background	Serotonin 1A receptors (5-HT(1A)) are implicated in the pathophysiology of major depressive disorder (MDD) and in the action of selective serotonin reuptake inhibitors (SSRI). SSRI desensitize 5-HT(1A) and down-regulate 5-HT transporters (5-HTT) with the latter persisting for weeks after discontinuation of SSRI. MDD subjects are more likely to be homozygous for the functional 5-HT(1A) G(-1019) allele of the promoter polymorphism and are postulated to have higher 5-HT(1A) than healthy volunteers (controls). We measure 5-HT(1A) in MDD, assess the effects of antidepressant exposure (AE), and examine the role of the C(-1019)G polymorphism.
Sample Information	28 medication-free MDD subjects during a current major depressive episode and 43 controls
Method Detail	Genotyped and determined 5-HT(1A) binding potential (BP) by positron emission tomography (PET) using [carbonyl-C-11]-WAY-100635 in 28 medication-free MDD subjects during a current major depressive episode and 43 controls.
Method Keywords	positron emission tomography (PET); genotyping
Result	No difference in BP between controls and MDD subjects (p = .235). There was a difference in BP comparing the controls, antidepressant naive (AN) MDD subjects, and subjects with AE across all regions (p = .013). Post hoc testing reveals higher BP in AN compared to controls (p = .008) and to AE (p = .007). The GG genotype is overrepresented in MDD subjects (p = .059), and BP appears higher with the G allele.
Conclusions	AN have higher 5-HT(1A) than controls and AE suggesting a model of depression characterized by an over expression of autoinhibitory somatodendritic 5-HT(1A) receptors, perhaps due to the higher expressing G allele, that may result in reduced terminal field 5-HT release. AE appears to have long-term effects on 5-HT(1A).

Relationships reported by Parsey, 2006