Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology?

Abstract

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans

“…However, effect sizes are generally small and not all studies have replicated the effect of reduced hippocampal volume in PTSD (Mohlenhoff, Chao, Buckley, Weiner, & Neylan, 2014; Schuff et al, 2001). Moreover, while some studies suggest that smaller hippocampal volume is a risk factor for PTSD (Gilbertson et al, 2002), others indicate that it is a correlate of current PTSD that may resolve when symptoms resolve (Apfel et al, 2011).…”

Understanding Recent Insights in Sleep and Posttraumatic Stress Disorder from a Research Domain Criteria (RDoC) Framework

“…Many previous studies have demonstrated reduced hippocampal volume in PTSD, especially in severe cases [26]. However, recent findings suggest that difficulties with sleep may substantially account for the relationship between PTSD and hippocampal volume [27]. Sleep difficulties, especially insomnia, may play a greater role than trauma-related symptoms in structural changes; however, causality and implications for the interplay between arousal, negative valence, and cognitive systems remain unclear.…”

Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure, Amyloid, and Inflammation

“…The sleep problems observed in PTSD may also contribute to dementia risk [7, 24, 26, 27]. One possible mechanism by which this occurs could involve damage to the hippocampus.…”

“…Few studies have systematically examined the role of sleep in the relationship between PTSD and hippocampal volume [24, 58, 59]. However, there are important reasons to suspect that it could play a key role.…”