Advanced melatonin onset relative to sleep in women with unmedicated major depressive disorder

Studies on circadian timing in depression have produced variable results, with some investigations suggesting phase advances and others phase delays. This variability may be attributable to differences in participant diagnosis, medication use, and methodology between studies. This study examined circadian timing in a sample of unmedicated women with and without unipolar major depressive disorder. Participants were aged 18-28 years, had no comorbid medical conditions, and were not taking medications. Eight women were experiencing a major depressive episode, nine had previously experienced an episode, and 31 were control participants with no history of mental illness. Following at least one week of actigraphic sleep monitoring, timing of salivary dim light melatonin onset (DLMO) was assessed in light of <1 lux. In currently depressed participants, melatonin onset occurred significantly earlier relative to sleep than in controls, with a large effect size. Earlier melatonin onset relative to sleep was also correlated with poorer mood for all participants. Our results indicate that during a unipolar major depressive episode, endogenous circadian phase is advanced relative to sleep time. This is consistent with the early-morning awakenings often seen in depression. Circadian misalignment may represent a precipitating or perpetuating factor that could be targeted for personalized treatment of major depression.