Salivary Cortisol and Regional Brain Volumes Among Veterans With and Without Posttraumatic Stress Disorder

BACKGROUND: Human studies have often found that brain regions rich in glucocorticoid receptors exhibit smaller volume in samples with past trauma and ongoing stress; however, relatively little research has addressed the hypothesis that such smaller volumes can be traced to elevated circulating glucocorticoid hormones (GCs). This issue takes on renewed interest in light of recent proposals to treat symptoms of stress disorders such as posttraumatic stress disorder (PTSD) with exogenous synthetic GCs. We sought to examine the relation of circulating GCs to brain macrostructure among veterans with and without PTSD. METHODS: Participants (n = 90) included combat veterans with and without PTSD. Veterans completed self-report surveys, home-based cortisol samples, reactive cortisol samples over the course of two serial Trier Social Stress Tests, a low-dose dexamethasone suppression test, and structural magnetic resonance brain imaging over the course of 3 to 5 days. RESULTS: No associations were observed between any salivary cortisol index and the volumes of the hippocampus or amygdala. A negative association was observed between evening basal cortisol and both FreeSurfer global volume and BrainImage supratentorial tissue volume. This effect was moderated by PTSD. Also observed was a positive association between reactive cortisol and these same brain volumes. CONCLUSIONS: Estimates of cortical but not hippocampal or amygdala volume were moderately associated with evening basal salivary cortisol and cortisol reactivity to a social stressor. Existing models relating GC receptor density, circulating cortisol levels, and regional brain volumes received little support.