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Decreased sensitivity of 5-HT_1D receptors in melancholic depression

University Department of Psychiatry, Oxford

Correspondence: Professor P.J. Cowen, University Department of Psychiatry, Warneford Hospital, Oxford OC37JX

Declaration of interest None.

Background Brain serotonin (5-HT) function is abnormal in major depression, but the involvement of different 5-HT receptor subtypes has been little studied. The availability of selective ligands now makes it possible to test the sensitivity of 5-HT_1D receptors in patients with depression.

Aims The aim of the study was to use the 5-HT_1D receptor agonist, zolmitriptan, to test the sensitivity of 5-HT_1D receptors in patients with depression 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 matched 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 reduction in zolmitriptan-induced growth hormone release.

Conclusions Patients with melancholic depression have impaired sensitivity of the post-synaptic 5-HT_1D receptors that mediate growth hormone release. The reduction in 5-HT_1D receptor sensitivity following SSRI treatment is probably an adaptive response to increased levels of synaptic 5-HT.

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