Decreased sensitivity of 5-HT1D receptors in melancholic depression

Background Brain serotonin (5-HT) function is abnormal in major depression, but the involvement of different 5-HT receptor subtypes has been little st udied. The availability of selective ligands now makes it possible to test the sensitivity of 5-HT1D receptors in patients with depression. Aims The aim of the study was to use the 5-HT1D receptor agonist, zolmitrip tan, to test the sensitivity of 5-HT1D receptors in patients with depressio n before and after treatment with selective serotonin reuptake inhibitors ( SSRIs). Method We measured the growth hormone response to zolmitriptan (5 mg orally ) in patients with major depression before and after SSRI treatment. A matc hed sample of healthy subjects acted as a control group. Results The growth hormone response to zolmitriptan was blunted in patients with a melancholic depressive syndrome. SSRI treatment produced a marked r eduction in zolmitriptan-induced growth hormone release. Conclusions Patients with melancholic depression have impaired sensitivity of the post-synaptic 5-HT1D receptors that mediate growth hormone release. the reduction in 5-HT1D receptor sensitivity following SSRI treatment is pr obably an adaptive response to increased levels of synaptic 5-HT. Declaration of interest None.