Sleep and Psychological Vulnerability to Traumatic Stress

The landmark longitudinal study by Ford and Kamerow¹ in 1989 established that insomnia was a strong predictor for the later development of major depression, and by implication, that disturbed sleep was central to the pathogenesis of depression and not an emergent epiphenomenon. The longitudinal relationship between insomnia and subsequent depression has now been replicated in numerous studies. There has been some evidence for a similar relationship between insomnia and risk for posttraumatic stress disorder (PTSD) following trauma exposure,² but not from large-scale studies where insomnia or mental disorders were assessed pre-exposure. One recent report found that higher scores on the Pittsburgh Sleep Quality Index³ during academy training in healthy police cadets predicted higher PTSD symptom levels after 2 years of active duty police service.⁴ However, this report did not have the sample size required to establish whether insomnia could predict full threshold PTSD.

Gehrman and colleagues⁵ report in this issue of SLEEP data from over 15,000 participants in the Millennium Cohort Study,⁶ which demonstrate that self-reported sleep duration and difficulties with sleep onset and maintenance prior to deployment predict new onset depression, PTSD, and generalized anxiety disorder (GAD). The report by Gehrman et al. has many strengths, including a very large sample size afforded by the combination of two large cohorts; exclusion of subjects who had prior diagnoses of depression, PTSD, or GAD, or prior deployments at baseline; and repeat sampling post-deployment to the wars in either Afghanistan or Iraq. The two cohorts produced a substantial number of new cases of depression, PTSD, and GAD, which provided sufficient statistical power to control for a number of possible confounds.

The results of Gehrman et al.⁵ confirmed that insomnia at baseline, and to some extent, short sleep duration, were potent risk factors for later onset of depression, PTSD, and GAD. Further, there were interesting nuances to the pattern of predictors for these three clinical outcomes. Future PTSD was predicted by subjective insomnia and short sleep duration (< 6 hours) in both cohorts, and by long sleep duration (> 8 hours) in one cohort. New onset depression was predicted by insomnia but not sleep duration in both cohorts. New onset GAD was predicted by insomnia in both cohorts, and short sleep duration in the first but not second cohort. Partisans on both sides of the current debate about the strengths and weaknesses of the DSM approach versus the developing research domain criteria (RDoC) spear-headed by the NIMH, may see these data as giving strengths to their argument. For example, perceived short sleep duration may in part be driven by heightened fear and perceived threat,⁷ which may account for why short sleep predicted later PTSD and anxiety, but not depression. Thus, individuals predisposed to be more vigilant to threat prior to deployment may be at higher risk for combat-related PTSD and anxiety, but not depression. The alternative perspective is that insomnia at baseline is a nonspecific risk factor for later occurrence of mood and anxiety symptoms that cross multiple diagnostic entities.

The sleep duration findings of Gehrman et al.⁵ are intriguing but do not support a strong argument that the three mental disorder outcomes have distinct pathogenetic mechanisms. One issue that remains unclear from their results is the extent of comorbidity across the three disorders. They have different samples sizes for the new cases of PTSD, depression, and GAD, and the multivariate modeling for the three outcomes are presented in separate tables. It is not clear if individuals who met criteria for more than one of the outcomes were included in more than one of the models. Aside from categorical comorbidity, the degree of overlap on dimensional measures of distress is also not presented.

Another intriguing aspect of the findings of Gehrman et al.⁵ pertains to the interaction of baseline sleep and combat exposure for predicting the three clinical diagnostic outcomes. Combat exposure predicted PTSD and depression in both cohorts, but, surprisingly, post-deployment anxiety in only one cohort. This contrasts with longitudinal studies of civilian trauma such as Breslau's Michigan health maintenance organization (HMO) sample⁸ and in Bryant's longitudinal study of injured patients seen in trauma centers in Australia,² which showed that trauma exposure increased risk for a number of mood and anxiety disorders. The Millennium Cohort investigators⁶ were limited to a combat exposure variable that had a low threshold for positive endorsement and no information on intensity and frequency of actual warzone experiences. Thus their finding that predeployment insomnia was comparably potent as combat exposure for post-deployment mental health disorders has to be taken with considerable caution. Nevertheless, their finding that baseline insomnia did not significantly modify the relationship between combat exposure and new onset PTSD and anxiety disorder introduces a question about whether predeployment insomnia treatment would result in improved resilience to combat exposure.

Post-combat insomnia in the Vietnam Twin study⁹ as well as the National Vietnam Readjustment Study,¹⁰ was only weakly associated with combat exposure. This adds support to the conclusion of Gehrman and colleagues⁵ that insomnia and combat exposure have independent associations with PTSD. Notwithstanding this note of caution, Gehrman and colleagues raise a compelling question about the possible utility of targeting pre-deployment insomnia to reduce risk for deployment related mental health disorders. The rapid development of brief behavioral treatments for insomnia,¹¹ aided by web or smart phone enhancements, increases the likelihood that this might be made widely available to high risk professions such as police and military.

The results of Gehrman et al.⁵ prompt important questions about how far we have progressed in understanding mechanisms of insomnia. Their data suggest that insomnia is the clinical expression of a pre-existing psychological vulnerability. They refer to the literature on REM fragmentation and risk for PTSD, which has solid support,¹² but this doesn't clarify specific mechanisms. The field still awaits definitive tests of putative mechanisms of sleep hyperarousal, such as inappropriate wake-on drive after the “flip” to the sleep state¹³ or disrupted signaling of specific mediators such as corticotropin releasing factor (CRF), hypo-cretin, adenosine, cytokines, glutamate, and γ-aminobutyric acid (GABA), to name a few candidates.^14,15 Results from the study by Gehrman and colleagues provide a strong argument that further discovery of the basic mechanisms involved with insomnia have great promise for helping us understand the biology of psychological vulnerability to traumatic stress.

CITATION

Neylan TC. Sleep and psychological vulnerability to traumatic stress. SLEEP 2013;36(7):967-968.

DISCLOSURE STATEMENT

Dr. Neylan has received research medications from Actelion and GlaxoSmithKline for studies funded by the Department of Defense and Department of Veterans Affairs.