Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder

Abstract

Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis.

Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control

“…3 Melatonin is a molecule produced at night by the vertebrate pineal gland 4,5 and in many other tissues as well. 6,7 In addition to entraining circadian rhythms 8 and functioning as an antioxidant, 9,10 several studies demonstrated that melatonin supplementation limits obesity in rodents without affecting food intake [11][12][13][14][15] and inconsistent changes in locomotor activity. 13,16 This suggests that melatonin may act as a thermogenic agent.…”

Melatonin promotes sorafenib‐induced apoptosis through synergistic activation of JNK/c‐jun pathway in human hepatocellular carcinoma

“…Melatonin is responsible for multiple physiological functions, including circadian rhythm, sleep, mood, sexual maturation, stress, insulin secretion, and reproduction . As a potent reactive oxygen species scavenger, melatonin exhibits protective effects against ischemia/reperfusion injury in experimental kidney transplantation model and liver resection model, and the use of high‐dose melatonin in clinical practice was confirmed to be safe .…”

Synergistic anti‐oomycete effect of melatonin with a biofungicide against oomycetic black shank disease

“…Melatonin (N‐acetyl‐5‐methoxytryptamine) can regulate biochemistry, physiology, and molecular biology of various organisms . Positively, functions of melatonin include regulation of circadian rhythms, immunomodulation, and scavenging free radicals . In plant, melatonin protects plants against pathogen attack mainly by regulating plant innate immunity to trigger the defense responses .…”

“…[8][9][10] Positively, functions of melatonin include regulation of circadian rhythms, immunomodulation, and scavenging free radicals. [11][12][13][14] In plant, melatonin protects plants against pathogen attack mainly by regulating plant innate immunity to trigger the defense responses. [15][16][17][18][19][20][21][22][23] For the application of exogenous melatonin on Arabidopsis thaliana and Malus prunifolia leaves, various defense genes contributing to resistance to pathogen are induced by exogenous melatonin.…”