Neuropeptide Y (NPY) shortens sleep latency but does not suppress ACTH and cortisol in depressed patients and normal controls

Abstract

Preclinical and clinical studies suggest that neuropeptide Y (NPY) exerts functional corticotropin-releasing hormone (CRH) antagonistic effects. NPY activity appears to be blunted in depression. Recently, we have found in young normal male controls after repetitive administration of NPY a shortened sleep latency and a decrease of time awake and, in the second half of the night, EEG delta-power; cortisol and ACTH levels were blunted. Since during depression there is an overactivity of CRH, we tested the capacity of NPY to affect sleep endocrine activity in patients with depression compared with controls. After one night of adaptation we administered hourly IV injections of placebo (PL) during the second night and of 50 microg NPY during the third night between 22:00 and 01:00 h. Throughout the night ACTH, cortisol and prolactin levels were measured, simultaneously the sleep electroencephalogram (EEG) was recorded. Depressed patients as well as healthy controls exhibited significant shortening of sleep onset latency (SOL) (mean+/-SD; controls: 41.9+/-48.2 min PL vs 22.1+/-17.3 min NPY; patients: 31.8+/-19.8 min PL vs 24.7+/-20.1 min NPY; P<0.06) and REM latency (controls: 79.3+/-27.5 min PL vs 69.0+/-19.4 min NPY; patients: 79.8+/-45.5 min PL vs 52.4+/-51.2 min NPY; P<0.05). Both patients and controls showed a trend to an increase of prolactin during the night. In contrast to our recent observation in young normal subjects time awake, ACTH and cortisol remained unchanged in patients and controls in response to NPY. Whereas also an adaptation effect may contribute to the shortening of SOL, this change and the prolactin elevation are in line with a CRH antagonistic and GABA(A) agonistic/benzodiazepine-like effect of NPY. The lack of effects on time awake and HPA hormones may be explained by the higher CRH activity due to age and depression in the investigated samples in comparison to our recent study in young subjects.