MK4MDD

Study Report

Reference
CitationHirvonen, 2008 PubMed
Full InfoHirvonen, J., Karlsson, H., Kajander, J., Lepola, A., Markkula, J., Rasi-Hakala, H., Nagren, K., Salminen, J.K. and Hietala, J. (2008) Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. Int J Neuropsychopharmacol, 11, 465-476.

Study
Hypothesis or Background Serotonin (5-HT) is involved in the pathophysiology of major depressive disorder (MDD). Among the numerous serotonergic receptors, the 5-HT1A receptor subtype is of interest because of its involvement in cognition, hippocampal neurogenesis, and mechanism of action of antidepressant drugs. Previous imaging studies have suggested altered availability of 5-HT1A receptors in MDD but prior antidepressant medication and chronicity of the illness may confound the interpretation.
Sample Information21 drug-naive primary-care patients with MDD along with 15 healthy control subjects.
Method DetailWe examined 21 drug-naive primary-care patients with MDD using positron emission tomography (PET) imaging with [carbonyl-11C]WAY-100635, a radioligand for 5-HT1A receptors, along with 15 healthy control subjects. Binding to receptors was assessed both regionally and at voxel level with the binding potential (BP) that was estimated using arterial blood input.
Method Keywordspositron emission tomography (PET)
ResultCompared with healthy controls, the BP of [carbonyl-11C]WAY-100635 was reduced in patients with MDD in most brain regions, ranging from -9% to -25%. Voxel-level analysis confirmed this finding by showing a widespread reduction of [carbonyl-11C]WAY-100635 BP. No statistically significant associations were observed between BP and total HAMD scores in the patients, but lower BP was associated with higher likelihood of insomnia.
ConclusionsThis study demonstrated a widespread reduction in the availability of serotonin 5-HT1A receptors in a relatively large sample of drug-naive primary-care patients with MDD, suggesting the involvement of this receptor subtype in the pathophysiology of the illness. Lack of correlation with overall severity of the illness may relate to a largely trait-like nature of this abnormality in depressive disorders.

Relationships reported by Hirvonen, 2008