Browsing by Author "Szabo, Steven T"

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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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    Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease.
    (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020-06) Hollander, Jonathan A; Cory-Slechta, Deborah A; Jacka, Felice N; Szabo, Steven T; Guilarte, Tomás R; Bilbo, Staci D; Mattingly, Carolyn J; Moy, Sheryl S; Haroon, Ebrahim; Hornig, Mady; Levin, Edward D; Pletnikov, Mikhail V; Zehr, Julia L; McAllister, Kimberly A; Dzierlenga, Anika L; Garton, Amanda E; Lawler, Cindy P; Ladd-Acosta, Christine
    The etiologic pathways leading to neuropsychiatric diseases remain poorly defined. As genomic technologies have advanced over the past several decades, considerable progress has been made linking neuropsychiatric disorders to genetic underpinnings. Interest and consideration of nongenetic risk factors (e.g., lead exposure and schizophrenia) have, in contrast, lagged behind heritable frameworks of explanation. Thus, the association of neuropsychiatric illness to environmental chemical exposure, and their potential interactions with genetic susceptibility, are largely unexplored. In this review, we describe emerging approaches for considering the impact of chemical risk factors acting alone and in concert with genetic risk, and point to the potential role of epigenetics in mediating exposure effects on transcription of genes implicated in mental disorders. We highlight recent examples of research in nongenetic risk factors in psychiatric disorders that point to potential shared biological mechanisms-synaptic dysfunction, immune alterations, and gut-brain interactions. We outline new tools and resources that can be harnessed for the study of environmental factors in psychiatric disorders. These tools, combined with emerging experimental evidence, suggest that there is a need to broadly incorporate environmental exposures in psychiatric research, with the ultimate goal of identifying modifiable risk factors and informing new treatment strategies for neuropsychiatric disease.
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    Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature.
    (CNS spectrums, 2020-06) Banov, Michael D; Young, Jonathan R; Dunn, Tyler; Szabo, Steven T
    Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.
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    Practical telehealth to improve control and engagement for patients with clinic-refractory diabetes mellitus (PRACTICE-DM): Protocol and baseline data for a randomized trial.
    (Contemporary clinical trials, 2020-11) Kobe, Elizabeth A; Edelman, David; Tarkington, Phillip E; Bosworth, Hayden B; Maciejewski, Matthew L; Steinhauser, Karen; Jeffreys, Amy S; Coffman, Cynthia J; Smith, Valerie A; Strawbridge, Elizabeth M; Szabo, Steven T; Desai, Shivan; Garrett, Mary P; Wilmot, Theresa C; Marcano, Teresa J; Overby, Donna L; Tisdale, Glenda A; Durkee, Melissa; Bullard, Susan; Dar, Moahad S; Mundy, Amy C; Hiner, Janette; Fredrickson, Sonja K; Majette Elliott, Nadya T; Howard, Teresa; Jeter, Deborah H; Danus, Susanne; Crowley, Matthew J

    Background

    Persistent poorly-controlled type 2 diabetes mellitus (PPDM), or maintenance of a hemoglobin A1c (HbA1c) ≥8.5% despite receiving clinic-based diabetes care, contributes disproportionately to the national diabetes burden. Comprehensive telehealth interventions may help ameliorate PPDM, but existing approaches have rarely been designed with clinical implementation in mind, limiting use in routine practice. We describe a study testing a novel telehealth intervention that comprehensively targets clinic-refractory PPDM, and was explicitly developed for practical delivery using existing Veterans Health Administration (VHA) clinical infrastructure.

    Methods

    Practical Telehealth to Improve Control and Engagement for Patients with Clinic-Refractory Diabetes Mellitus (PRACTICE-DM) is an ongoing randomized controlled trial comparing two 12-month interventions: 1) standard VHA Home Telehealth (HT) telemonitoring/care coordination; or 2) the PRACTICE-DM intervention, a comprehensive HT-delivered intervention combining telemonitoring, self-management support, diet/activity support, medication management, and depression management. The primary outcome is HbA1c. Secondary outcomes include diabetes distress, self-care, self-efficacy, weight, depressive symptoms, implementation barriers/facilitators, and costs. We hypothesize that the PRACTICE-DM intervention will reduce HbA1c by >0.6% versus standard HT over 12 months.

    Results

    Enrollment for this ongoing trial concluded in January 2020; 200 patients were randomized (99 to standard HT and 101 to the PRACTICE-DM intervention). The cohort has a mean age of 58 and is 23% female and 72% African American. Mean baseline HbA1c and BMI were 10.2% and 34.8 kg/m2.

    Conclusions

    Because it comprehensively targets factors underlying PPDM using existing clinical infrastructure, the PRACTICE-DM intervention may be well suited to lower the complications and costs of PPDM in routine practice.
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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.