Blunted Nocturnal Salivary Melatonin Secretion Profiles in Military-Related Posttraumatic Stress Disorder

Abstract

Background: Sleep disturbances are a hallmark of posttraumatic stress disorder (PTSD), yet few studies have evaluated the role of dysregulated endogenous melatonin secretion in this condition. Methods: This study compared the sleep quality and nocturnal salivary melatonin profiles of Canadian Armed Forces (CAF) personnel diagnosed with PTSD, using the Clinician Administered PTSD Scale (CAPS score ≥50), with two healthy CAF control groups; comprising, a “light control” (LC) group with standardized evening light exposure and “normal control” (NC) group without light restriction. Participants were monitored for 1-week using wrist actigraphy to assess sleep quality, and 24-h salivary melatonin levels were measured (every 2h) by immunoassay on the penultimate day in a dim-light (< 5 lux) laboratory environment. Results: A repeated measures design showed that mean nocturnal melatonin concentrations for LC were higher than both NC (p = .03) and PTSD (p = .003) with no difference between PTSD and NC. Relative to PTSD, NC had significantly higher melatonin levels over a 4-h period (01 to 05 h), whereas the LC group had higher melatonin levels over an 8-h period (23 to 07 h). Actigraphic sleep quality parameters were not different between healthy controls and PTSD patients, likely due to the use of prescription sleep medications in the PTSD group. Conclusions: These results indicate that PTSD is associated with blunted nocturnal melatonin secretion, which is consistent with previous findings showing lower melatonin after exposure to trauma and suggestive of severe chronodisruption. Future studies targeting the melatonergic system for therapeutic intervention may be beneficial for treatment-resistant PTSD.

Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption

“…Neuroendocrine PTSD findings consistently demonstrate altered HPA axis reactivity with enhanced negative feedback inhibition and blunted circadian CORT rhythm and CAR, while some studies – but not all – have shown decreased circulating concentrations of CORT (Heim & Nemeroff, 2009 ; Pitman et al, 2012 ; Raison & Miller, 2003 ; Thomas et al, 2012 ; van Liempt et al, 2013 ; Yehuda, 2002 ; Yehuda, Golier, & Kaufman, 2005 ). Interestingly, a recent study showed also blunted nocturnal MLT secretion profiles in military-related PTSD (Paul et al, 2019 ). These findings are similar to many human SD studies, suggesting that the HPA axis- and GC-signalling-specific alterations in PTSD may be partially mediated by sleep and circadian disruption (Chrousos & Kino, 2009 ; Germain et al, 2008 ; Otte et al, 2005 ).…”

Salivary Biomarkers of Stress, Anxiety and Depression

“…However, that correlation was not as strong as in the case with depression. Paul et al [ 59 ], in turn, found a significant reduction in the levels of salivary melatonin at night in soldiers suffering from post-traumatic stress disorder (PTSD). The results published by researchers seem to be very promising.…”

Biological Markers in Anxiety Disorders

“…Interestingly, in the case of depression, this correlation was much stronger. Moreover, Paul et al showed a significant reduction in the level of melatonin in the saliva of soldiers with post-traumatic stress disorder (PTSD) [ 49 ]. The results released by scientists seem to be extremely propitious; therefore, it is worth expanding the scientific research on melatonin because melatonin in saliva could be a valuable biomarker in the future [ 50 ].…”