Brain neurokinin-1 receptor availability in never-medicated patients with major depression - A pilot study

Neurotransmitter substance P (SP) and its preferred neurokinin-1 receptor (NK1R) have been implicated in the treatment of affective and addiction disorders. Despite promising preclinical data on antidepressant action, the clinical trials of NK1R antagonists in major depression have been disappointing. There are no direct in vivo imaging studies on NK1R characteristics in patients with a major depressive disorder (MDD).

In this cross-sectional case-control study, we recruited nine never-medicated patients with moderate to severe MDD and nine matched healthy controls. NK1R availability (NK1R binding potential, BP_ND) was measured with in vivo 3-D positron emission tomography and a specific NK1 receptor tracer [¹⁸F]SPA-RQ. Clinical symptoms were assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D17).

NK1R-BP_ND did not differ statistically significantly between patients with MDD and healthy controls. HAM-D17 total scores (range 21-32) correlated positively with NK1R-BP_ND in cortical and limbic areas. HAM-D17 subscale score for anxiety symptoms correlated positively with NK1R-BP_ND in specific brain areas implicated in fear and anxiety.

Small sample size. Low variability in the clinical HAM-D subscale ratings may affect the observed correlations.

Our preliminary results do not support a different baseline expression of NK1Rs in a representative sample of never-medicated patients with MDD during a current moderate/severe depressive episode. The modulatory effect of NK1Rs on affective symptoms is in line with early positive results on antidepressant action of NK1 antagonists. However, the effect is likely to be too weak for treatment of MDD with NK1R antagonists alone in clinical practice.