Abstract

BackgroundAn altered postsynaptic 5-HT1A receptor function along with hypercortisolemia has been associated with major depressive disorder (MDD). However, several methodological considerations related to data interpretation arise when subjects previously exposed to psychotropic medication are included in the study population. To address those issues we designed a study in a well defined cohort of first-episode, treatment-naïve MDD patients. MethodsThis cross-sectional case–control pharmacologic challenge study was designed to investigate the prolactin (PRL) response to buspirone in 21 non-late-life adult, treatment-naïve MDD patients with the first affective episode and in 20 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20. ResultsNo significant difference in PRL response to buspirone between first-episode, treatment-naïve patients with MDD and controls, was observed. The correlation between basal cortisol levels and PRL response was not observed in MDD group while significant negative correlation was found in healthy controls. The significantly higher PRL response to buspirone was observed in melancholic patients as compared to non-melancholic subjects. LimitationsThe current study is limited by its cross-sectional design, small sample size, factors related to neuroendocrine challenge methodology, and no placebo control. ConclusionThese results indicate no consistent changes in the hormonal response to the 5-HT1A agonist buspirone in major depression. Taken into account the interpretation of the buspirone test the present study does not support the hypothesis of an altered functional activity with down-regulation of the postsynaptic 5-HT1A receptor and/or in the postsynaptic receptor signal transduction in the hypothalamus in the pathogenesis of MDD.

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