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Context Many studies have moved toward saliva and peripheral blood sampling for studying cortisol, even in relation to disorders of the brain. However, the degree to which peripheral cortisol reflects central cortisol levels has yet to be comprehensively described. Data describing the effect that biological characteristics such as age and sex have on cortisol levels across compartments is also limited. Objective To assess the relationships of cortisol levels across cerebrospinal fluid (CSF), saliva, and plasma (total and free) compartments and describe the effects of age and sex on these relationships. Design Multisite cross-sectional observation study. Setting Samples collected in academic outpatient settings in 2001-2004. Patients or Other Participants Healthy community volunteers (n = 157) of both sexes, aged 20-85 years. Interventions None. Main Outcome Measures This study was a secondary analysis of data collected from a previously published study. Results CSF cortisol correlated more strongly with plasma (r = 0.49, P <.0001) than with saliva cortisol levels. Sex but not age was a significant modifier of these relationships. CSF cortisol levels trended higher with older age in men (R2 = 0.31, P <.001) but not women. Age-related cortisol binding globulin trends differed by sex but did not correlate with sex differences in cortisol levels in any compartment. Conclusion Variability in the correlations between central and peripheral cortisol discourages the use of peripheral cortisol as a direct surrogate for central cortisol measures. Further investigation of how mechanistic drivers interact with biological factors such as sex will be necessary to fully understand the dynamics of cortisol regulation across fluid compartments. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the efficacy and tolerability of prazosin for prophylaxis of headaches following mild traumatic brain injury in active‐duty service members and military veterans. Background: Prazosin is an alpha‐1 adrenoreceptor antagonist that reduces noradrenergic signaling. An open‐label trial in which prazosin reduced headache frequency in veterans following mild traumatic brain injury provided the rationale for this pilot study. Methods: A 22‐week parallel‐group randomized controlled trial which included 48 military veterans and active‐duty service members with mild traumatic brain injury–related headaches was performed. The study design was based on International Headache Society consensus guidelines for randomized controlled trials for chronic migraine. Following a pre‐treatment baseline phase, participants with at least eight qualifying headache days per 4 weeks were randomized 2:1 to prazosin or placebo. After a 5‐week titration to a maximum possible dose of 5 mg (morning) and 20 mg (evening), participants were maintained on the achieved dose for 12 weeks. Outcome measures were evaluated in 4‐week blocks during the maintenance dose phase. The primary outcome measure was change in 4‐week frequency of qualifying headache days. Secondary outcome measures were percent participants achieving at least 50% reduction in qualifying headache days and change in Headache Impact Test‐6 scores. Results: Intent‐to‐treat analysis of randomized study participants (prazosin N = 32; placebo N = 16) demonstrated greater benefit over time in the prazosin group for all three outcome measures. In prazosin versus placebo participants, reductions from baseline to the final rating period for 4‐week headache frequency were −11.9 ± 1.0 (mean ± standard error) versus −6.7 ± 1.5, a prazosin minus placebo difference of −5.2 (−8.8, −1.6 [95% confidence interval]), p = 0.005 and for Headache Impact Test‐6 scores were −6.0 ± 1.3 versus +0.6 ± 1.8, a difference of −6.6 (−11.0, −2.2), p = 0.004. The mean predicted percent of participants at 12 weeks with ≥50% reduction in headache days/4 weeks, baseline to final rating, was 70 ± 8% for prazosin (21/30) versus 29 ± 12% for placebo (4/14), odds ratio 5.8 (1.44, 23.6), p = 0.013. The trial completion rate of 94% in the prazosin group (30/32) and 88% in the placebo group (14/16) indicated that prazosin was generally well tolerated at the administered dose regimen. Morning drowsiness/lethargy was the only adverse effect that differed significantly between groups, affecting 69% of the prazosin group (22/32) versus 19% of the placebo group (3/16), p = 0.002. Conclusions: This pilot study provides a clinically meaningful efficacy signal for prazosin prophylaxis of posttraumatic headaches. A larger randomized controlled trial is needed to confirm and extend these promising results. [ABSTRACT FROM AUTHOR]

Objective: Examine relationships between self-perceived irritability, prospective memory, and quality of life (QOL) following mild traumatic brain injury (mTBI). Methods: 75 OEF/OIF/OND-era Veterans (56 deployment-related mTBI; 19 no history of TBI), were administered a battery of neuropsychological tests and self-report measures of mood and QOL. Self-perceived irritability was measured using the Neurobehavioral Symptom Inventory. Prospective memory (PM) was measured using the Memory for Intentions Test (MIST). Results: Self-perceived irritability was significantly higher for Veterans with, versus without, a history of deployment-related mTBI. Among Veterans with a history of mTBI, self-perceived irritability was inversely associated with PM performance, even after adjusting for PTSD severity. Greater self-perceived irritability was also associated with higher depressive symptoms and reduced QOL for perceived physical health, psychological health, social support, and environmental factors; however, only social support remained significant after adjusting for PTSD severity. Depression symptom severity was not significantly associated with PM, suggesting that PM may be uniquely related to self-perceived irritability rather than mood dysregulation more generally. Conclusions: Findings provide preliminary evidence of a relationship between PM and self-perceived irritability in Veterans with a history of mTBI. PM and irritability may be related via their mutual reliance on high-level cognitive control. Results illustrate possible cognitive and affective factors contributing to psychological and interpersonal challenges for this population. Future investigations with larger and more diverse samples are needed to replicate findings and explore potential mechanisms linking irritability and PM following mTBI. [ABSTRACT FROM AUTHOR]