Assessing the Interplay of Sleep, Hormones, and Depression

A relatively recent publication in Pharmacopsychiatry (2013 May;46 Suppl 1:S30-5) explores the influence of hormones and depression on sleep. Ahead, study author Professor Axel Steiger discusses key considerations and their implications for patient care.

Please describe the cycle of sleep/wake promotion and the role of peptides and hormones in it.

A bi-directional interaction exists between sleep, which is assessed by sleep-EEG recordings and endocrine activity. Various peptides and steroids participate in sleep regulation. It is thought that during the first half of the night the influence of growth hormone-releasing hormone (GHRH) preponderates resulting in high amounts of deep sleep (slow-wave sleep). SWS and the growth hormone (GH) surge, the maxiumus of GH release during 24 hours. The peptides galanin and ghrelin may be co-factors to GHRH.

Neuropeptide Y (NPY) influences timing of sleep onset. During the second half of the night the key hormone of the stress axis (the hypothalamo-pituitary adrenocortical [HPA] system), corticotropin-releasing hormone (CRH) and its cofactor somatostatin dominate.

Changes in the GHRH/CRH balance during depression and aging result in similar alternations of sleep-endocrine activity as shallow sleep, low GH, and elevated cortisol levels.

Is it possible to modulate peptides in order to promote sleep? What is the state of the science?

In experiments in animals and humans, certain peptides, particularly GHRH, promote sleep. In young healthy male subjects, after repetitive intravenous injections of GHRH, sleep is promoted. There is, however, no method which can be applied in clinical practice. Interestingly in a previous study a synthetic peptide, a GH secretagogue promoted sleep in young healthy volunteers after oral administration. Furthermore intranasal administration of peptides may be a method to modulate sleep.

Could hormonal modulation play a role in managing sleep patterns? If so, how?

Various studies show that peptides and steroids are involved in sleep regulation. Changes in the activity of certain hormones during aging, menopause, and disorders related with endocrine aberrances (endocrine disorders, depression) result in changes of sleep, in most cases in disturbed sleep. Hormone replacement can help to improve sleep, for example, in menopausal women. This was shown as estrogen and progesterone replacement helped to restore sleep of menopausal women. It appears feasible to use also other hormones, for example, the steroid pregnenolone, as a hypnotic.

How does depression fit into the cyclical pattern of sleep disruption/excessive sleepiness? Is treatment of depression expected to improve sleep quality?

Most patients with depression suffer from insomnia. CRH overactivity is thought to contribute to this symptom. In about 10 percent of depressed patients, particularly those with an atypical depression, hypersomnia occurs.

Treatment of depression may improve or impair sleep quality, depending on the anti-depressant. Some substances (e.g., mirtazapine, amitriptyline) promote sleep, whereas others (e.g., serotonin or noradrenaline reuptake inhibitors) tend to impair sleep.

We showed that sleep in remitted drug-free patients does not differ from that during acute depression. Possibly a scar exists in the sleep of remitted patients. During acute depression patients may suffer from impaired sleep; after recovery their cognition is improved. Therefore they feel possibly more comfortable with their persisting impaired sleep pattern.

Axel Steiger is research group leader, senior psychiatrist, Head of the Sleep Outpatient Clinic, as well as Head of the Sleep Laboratory at the Max Planck Institute of Psychiatry in Munich.