Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder

Orexins are neuropeptides selectively expressed in a small number of neurons in the lateral-posterior hypothalamus. We measured orexin-A in the cerebrospinal fluid (CSF) of 66 patients with major depressive disorder (MDD), dysthymia and adjustment disorder after a suicide attempt. Blood samples confirmed that the patients were free from antidepressive and neuroleptic medication at the time of the lumbar punctures. CSF levels of orexin-A were significantly lower in patients with MDD than in patients with adjustment disorder and dysthymia. Orexin correlated significantly with CSF levels of somatostatin, delta steep inducing peptide-like immunoreactivity (DSIP-LI) and corticotrophin releasing factor (CRF), but not with leptin or vasopressin. Plasma Levels of thyroid-stimulating hormone (TSH) were not reduced in MDD patients, and did not correlate with CSF-orexin. Our results suggest that suicidal patients with MDD have distinct neurobiological features, involving compromised levels of hypothalamic peptides regulating the state of arousal. (c) 2007 Elsevier B.V. and ECNP. All rights reserved.