Decreased nocturnal growth hormone secretion and sleep fragmentation in combat-related posttraumatic stress disorder; potential predictors of impaired memory consolidation
Introduction
In the last few years evidence has accumulated for the importance of sleep on memory formation. Overnight sleep or a daytime nap strengthens newly formed memory (Stickgold, 2005, Gais et al., 2006a, Gais et al., 2006b, Rasch et al., 2007a, Rasch et al., 2007b, Lahl et al., 2008). During sleep hippocampal neurons reactivate and newly acquired information is reorganized and transferred to neocorticol areas for permanent storage (Gais et al., 2007, Takashima et al., 2009). In addition, the ability of the hippocampus to store new information is dependent on previous sleep quality; functional MRI studies have shown that interrupted sleep and sleep deprivation lead to decreased encoding and decreased hippocampus activation during encoding (Yoo et al., 2007, Van Der Werf et al., 2009). Growth hormone (GH), which stimulates neuronal survival and growth, has a peak during the first half of the night (Van Cauter et al., 2004) – a period of enhanced declarative memory consolidation (Rasch et al., 2007a, Rasch et al., 2007b), and GH receptors are present in the hippocampus (Lai et al., 1993), a brain region implicated in memory consolidation and brain plasticity. A relationship between GH secretion and sleep dependent memory formation has been suggested in a preclinical study (Kim et al., 2010). Some disorders that are accompanied by disturbed sleep, such a obstructive sleep apnea syndrome (OSAS), and major depressive disorder (MDD), are associated with both impaired cognitive functioning, sleep fragmentation and a blunted GH peaks during the night (Steiger, 2007, Lanfranco et al., 2010).
One of the hallmarks of PTSD is insomnia, which negatively contributes to complaints such as intrusive memories, avoidance and hyper-alertness. In addition, PTSD patients often suffer from memory complaints that can affect normal functioning in work, social situations and at home (Geuze et al., 2009, Belleville et al., 2009). Typically, patients remain alert at night and re-experience their traumatic memory during nightmares. Yet, despite sometimes severe sleep complaints, polysomnographic studies have reported only mild disturbances in sleep structure, for a meta analyses see (Kobayashi et al., 2007). However, other studies found evidence for fragmented sleep with an increased number of nocturnal awakenings and arousals (Mellman et al., 1995, Germain and Nielsen, 2003, Habukawa et al., 2007).
To date, nocturnal GH secretion and overnight memory consolidation has not been studied in PTSD. We hypothesize that in PTSD patients sleep fragmentation is related to decreased GH secretion. Furthermore, we hypothesize that decreased GH secretion is associated with poor memory performance.
Section snippets
Participants
Veterans with PTSD were recruited through the outpatient clinic of the Military Mental Healthcare, Utrecht, The Netherlands. Trauma controls (TC; veterans without PTSD) and healthy controls (HC; service members never deployed or civilians) were recruited through advertisements. Controls were matched with the PTSD group for age, year of deployment (TC) and region of deployment (TC). After a verbal and written description of the study, written informed consent was obtained. All participants were
Results
From the 22 PTSD patients who were recruited to participate, one was excluded because of cannabis dependence, one was lost for follow up, one was excluded due to a BMI of 40, one reported symptom relieve after psychotherapy before the study was finished, one patient was excluded due to OSAS, and three patients screened positive for PLMD. A total of 14 PTSD patients were included. Three patients used medication for hypertension; beta-blocker (n = 3), Calcium channel antagonist (n = 2), ACE inhibitor
Discussion
This is the first study to report on decreased nocturnal GH secretion in PTSD. Furthermore, a correlation between GH secretion and sleep fragmentation was observed, while TST and SWS was not altered in PTSD patients. It has been suggested that sleep quality and decreased nocturnal GH secretion may negatively affect cognitive functioning. To this end, we performed a declarative memory task before sleep with a post sleep delayed recall and found that both sleep fragmentation and GH secretion
Role of the funding source
This study was funded by a grant from the Dutch Ministry of Defense that had no further role in the study design, in the collection of the data, the analyses and the interpretation of data; in writing of the report, and in the decision to submit the paper for publication.
Conflict of interest
All authors declare that there are no conflicts of interests.
Acknowledgements
The authors thank Jos van Gorp for the analyses of sleep registrations, and thank Inge Maitimu for organizing the growth hormone analyses.
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