Browsing by Author "Kilts, Jason D"

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    A pilot randomized controlled trial with paroxetine for subthreshold PTSD in Operation Enduring Freedom/Operation Iraqi Freedom era veterans
    (Psychiatry Research, 2012-12-31) Naylor, Jennifer C; Dolber, Trygve R; Strauss, Jennifer L; Kilts, Jason D; Strauman, Timothy J; Bradford, Daniel W; Szabo, Steven T; Youssef, Nagy A; Connor, Kathryn M; Davidson, Jonathan RT; Marx, Christine E
    Subthreshold posttraumatic stress disorder (PTSD) is associated with increased risk for suicidality, depression, and functional impairment. We thus conducted a small (N=12) pilot randomized controlled trial (RCT) with paroxetine for subthreshold PTSD in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) era veterans. Hospital Anxiety and Depression Scale (HADS) scores improved by 30.4% in the paroxetine group. Paroxetine may have promise for subthreshold PTSD.
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    Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.
    (Pain Med, 2016-01) Naylor, Jennifer C; Kilts, Jason D; Szabo, Steven T; Dunn, Charlotte E; Keefe, Francis J; Tupler, Larry A; Shampine, Lawrence J; Morey, Rajendra A; Strauss, Jennifer L; Hamer, Robert M; Wagner, H Ryan; MIRECC Workgroup; Marx, Christine E
    BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.
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    Widespread Cortical Thickness Is Associated With Neuroactive Steroid Levels.
    (Frontiers in Neuroscience, 2019-01) Morey, Rajendra A; Davis, Sarah L; Haswell, Courtney C; Naylor, Jennifer C; Kilts, Jason D; Szabo, Steven T; Shampine, Larry J; Parke, Gillian J; Sun, Delin; Swanson, Chelsea A; Wagner, Henry R; Mid-Atlantic MIRECC Workgroup; Marx, Christine E
    Background:Neuroactive steroids are endogenous molecules with regenerative and neuroprotective actions. Both cortical thickness and many neuroactive steroid levels decline with age and are decreased in several neuropsychiatric disorders. However, a systematic examination of the relationship between serum neuroactive steroid levels and in vivo measures of cortical thickness in humans is lacking. Methods:Peripheral serum levels of seven neuroactive steroids were assayed in United States military veterans. All (n = 143) subsequently underwent high-resolution structural MRI, followed by parcellelation of the cortical surface into 148 anatomically defined regions. Regression modeling was applied to test the association between neuroactive steroid levels and hemispheric total gray matter volume as well as region-specific cortical thickness. False discovery rate (FDR) correction was used to control for Type 1 error from multiple testing. Results:Neuroactive steroid levels of allopregnanolone and pregnenolone were positively correlated with gray matter thickness in multiple regions of cingulate, parietal, and occipital association cortices (r = 0.20-0.47; p < 0.05; FDR-corrected). Conclusion:Positive associations between serum neuroactive steroid levels and gray matter cortical thickness are found in multiple brain regions. If these results are confirmed, neuroactive steroid levels and cortical thickness may help in monitoring the clinical response in future intervention studies of neuroregenerative therapies.