However, given the substantial age difference between the groups (patients: 51.3 ± 16.2 years; healthy controls: 36.4 ± 11.8 years) and the fact that all MDD patients had a history of medication use, the question of whether there is a difference in CSF hypocretin-1 levels between MDD patients and healthy individuals remains to be further investigated (Schmidt et al., 2011). Here, HCRT is linked to major depressive disorder.