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

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.