IU Indianapolis ScholarWorks :: Browsing by Subject "Post-traumatic stress disorder"

Browsing by Subject "Post-traumatic stress disorder"

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4335 Role of PSD95 and nNOS interaction in gene regulation following fear conditioning and implications for molecular mechanisms underlying PTSD
(Cambridge University Press, 2020-07-29) Patel, Jheel; Dustrude, Erik; Haulcomb, Melissa; Li, Liangping; Jiang, Guanglong; Liu, Yunlong; Lai, Yvonne; Molosh, Andrei; Shekhar, Anantha; Medicine, School of Medicine
OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the amygdala in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecular PSD95-nNOS inhibitor, co-immunoprecipitation, Western blotting, and RNA-sequencing. RESULTS/ANTICIPATED RESULTS: We show that fear conditioning enhances the PSD95-nNOS interaction and that the small-molecule ZL006 inhibits this interaction. Treatment with ZL006 also attenuates rodent cued-fear consolidation and prevents fear-mediated shifts in glutamatergic receptor and current densities in the basolateral amygdala (BLA). With RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored by systemic ZL006 treatment. Network data and gene ontology enrichment analysis with Ingenuity Pathway Analysis and DAVID software found that cell-cell interaction, cognition-related pathways, and insulin-like growth factor binding were significantly altered. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results reveal novel genetic targets that underlie plasticity of fear-memory circuitry via their contribution of NMDAR-mediated fear consolidation and can inform future strategies for targeting fear related disorders like PTSD. CONFLICT OF INTEREST DESCRIPTION: Anantha Shekhar and Yvonne Lai are co-founders of Anagin, Inc., which is developing some of the related molecules for the treatment of PTSD.
Classification and Prediction of Post-Trauma Outcomes Related to PTSD Using Circadian Rhythm Changes Measured via Wrist-Worn Research Watch in a Large Longitudinal Cohort
(IEEE, 2021) Cakmak, Ayse S.; Perez Alday, Erick A.; Da Poian, Giulia; Rad, Ali Bahrami; Metzler, Thomas J.; Neylan, Thomas C.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Linnstaedt, Sarah D.; Jovanovic, Tanja; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Lewandowski, Christopher A.; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I., Jr.; Haran, John P.; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Gentile, Nina T.; McGrath, Meghan E.; Seamon, Mark J.; Mohiuddin, Kamran; Chang, Anna M.; Pearson, Claire; Domeier, Robert M.; Bruce, Steven E.; O’Neil, Brian J.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; Ressler, Kerry J.; Mclean, Samuel A.; Li, Qiao; Clifford, Gari D.; Emergency Medicine, School of Medicine
Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.
Evolution of Irritability, Anger, and Aggression after Traumatic Brain Injury: Identifying and Predicting Subgroups
(Mary Ann Liebert, 2021) Miles, Shannon R.; Hammond, Flora M.; Neumann, Dawn; Silva, Marc A.; Tang, Xinyu; Kajankova, Maria; Dillahunt-Aspillaga, Christina; Nakase-Richardson, Risa; Physical Medicine and Rehabilitation, School of Medicine
The current prospective, multi-center, longitudinal cohort study examined how veterans/service members (V/SM) changed in their irritability, anger, and aggression (IAA) scores from admission to discharge in post-acute rehabilitation settings. The goals were to identify trajectory subgroups, and explore if there were different predictors of the subgroups. V/SM (n = 346) from five Veterans Affairs TBI Model Systems Polytrauma Rehabilitation Centers participated. The sample was mostly men (92%) and identified as white (69%), black (13%), and other races (18%). Median age was 28 years, and 78% had sustained a severe TBI. Staff rated IAA at admission and discharge using the Mayo-Portland Adaptability Inventory-4 item#15. Four IAA trajectory subgroups were identified: (1) no IAA at admission or discharge (n = 89, 25.72%), (2) resolved IAA (n = 61, 17.63%), (3) delayed onset IAA (n = 31, 8.96%), and (4) persistent IAA (n = 165, 47.69%). Greater post-traumatic stress disorder (PTSD) symptoms were the only consistent predictor of belonging to all the subgroups who had IAA compared with the no IAA subgroup. We conclude that IAA had different trajectories after a TBI. The majority of V/SM had persistent impairment from IAA, a quarter of the sample had no impairment from IAA, and fewer participants had resolving or worsening IAA. Findings emphasize the importance of educating providers and family of the different ways and times that IAA can manifest after TBI. Timely diagnosis and treatment of PTSD symptoms during and after rehabilitation are critical treatment targets.
Gene Expression Differences Between Young Adults Based on Trauma History and Post-traumatic Stress Disorder
(Frontiers Media, 2021-04-08) Bountress, Kaitlin E.; Vladimirov, Vladimir; McMichael, Gowon; Taylor, Z. Nathan; Hardiman, Gary; Chung, Dongjun; Adams, Zachary W.; Kmett Danielson, Carla; Amstadter, Ananda B.; Psychiatry, School of Medicine
Background: The purpose of this study was to identify gene expression differences associated with post-traumatic stress disorder (PTSD) and trauma exposure (TE) in a three-group study design comprised of those with and without trauma exposure and PTSD. Methods: We conducted gene expression and gene network analyses in a sample (n = 45) composed of female subjects of European Ancestry (EA) with PTSD, TE without PTSD, and controls. Results: We identified 283 genes differentially expressed between PTSD-TE groups. In an independent sample of Veterans (n = 78) a small minority of these genes were also differentially expressed. We identified 7 gene network modules significantly associated with PTSD and TE (Bonferroni corrected p ≤ 0.05), which at a false discovery rate (FDR) of q ≤ 0.2, were significantly enriched for biological pathways involved in focal adhesion, neuroactive ligand receptor interaction, and immune related processes among others. Conclusions: This study uses gene network analyses to identify significant gene modules associated with PTSD, TE, and controls. On an individual gene level, we identified a large number of differentially expressed genes between PTSD-TE groups, a minority of which were also differentially expressed in the independent sample. We also demonstrate a lack of network module preservation between PTSD and TE, suggesting that the molecular signature of PTSD and trauma are likely independent of each other. Our results provide a basis for the identification of likely disease pathways and biomarkers involved in the etiology of PTSD.
Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk
(Frontiers Media, 2024-03-08) Garrison-Desany, Henri M.; Meyers, Jacquelyn L.; Linnstaedt, Sarah D.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Jovanovic, Tanja; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Gentile, Nina T.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; O’Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Joormann, Jutta; Harte, Steven E.; McLean, Samuel A.; Koenen, Karestan C.; Denckla, Christy A.; Emergency Medicine, School of Medicine
Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.
Post-traumatic stress disorder among individuals with traumatic spinal cord injury in Nepal: a cross-sectional study
(Springer Nature, 2023-04-06) Parajuli, Bikash; Acharya, Khagendra; Grooves, Christine C.; Dhakal, Raju; Shrestha, Jemina; Shrestha, Rahul; Manandhar, Mishu; Physical Medicine and Rehabilitation, School of Medicine
Study design: Cross-sectional study OBJECTIVES: To identify the prevalence of posttraumatic stress disorder (PTSD) among the individuals with traumatic spinal cord injury (TSCI) and to examine the relationships between demographic and clinical characteristics, and PTSD. Setting: Spinal Injury Rehabilitation Center (SIRC) and Dhulikhel Hospital, Kathmandu University Hospital (DH, KUH), Kavrepalanchowk, Nepal. Methods: Individuals above 18 years of age with TSCI of at least one month from trauma and admitted to SIRC and DH, KUH from June 2019 to May 2021 were included. The specific stress version of the PostTraumatic Stress Disorder Checklist (PCL), was utilized. To classify the neurological status of TSCI individuals, International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used. Hierarchical multiple regression analysis between independent variables and normalized PCL score was done to evaluate the predictors of PTSD. Results: Among 163 patients, the overall prevalence of PTSD was 27%, and the mean PCL score was 36 ± 13.9. Factors predictive of PTSD included gender, family type, ethnicity, and literacy rate. No significant association was found between the clinical characteristics and PTSD. Conclusions: PTSD appears to be considerably prevalent among individuals with TSCI in Nepal. Females, individuals from nuclear families, individuals with lower literacy, and individuals from lower caste are significantly vulnerable to developing PTSD. However, clinical characteristics do not appear to be influential in the development of PTSD.
Psychiatric symptoms and their association with sleep disturbances in intensive care unit survivors
(Dovepress, 2019-03-22) Wang, Sophia; Meeker, Jared W.; Perkins, Anthony J.; Gao, Sujuan; Khan, Sikandar H.; Sigua, Ninotchka L.; Manchanda, Shalini; Boustani, Malaz A.; Khan, Babar A.; Psychiatry, School of Medicine
Background: Sleep disturbances in critically ill patients are associated with poorer long-term clinical outcomes and quality of life. Studies are needed to better characterize associations and risk factors for persistent sleep disturbances after intensive care unit (ICU) discharge. Psychiatric disorders are frequently associated with sleep disturbances, but the role of psychiatric symptoms in sleep disturbances in ICU survivors has not been well-studied. Objective: To examine the association between psychiatric symptoms and sleep disturbances in ICU survivors. Methods: 112 adult ICU survivors seen from July 2011 to August 2016 in the Critical Care Recovery Center, an ICU survivor clinic at the Eskenazi Hospital in Indianapolis, IN, USA, were assessed for sleep disturbances (insomnia, hypersomnia, difficulty with sleep onset, difficulty with sleep maintenance, and excessive daytime sleepiness) and psychiatric symptoms (trauma-related symptoms and moderate to severe depressive symptoms) 3 months after ICU discharge. A multivariate logistic regression model was performed to examine the association between psychiatric symptoms and sleep disturbances. Analyses were controlled for age, hypertension, history of depression, and respiratory failure. Results: ICU survivors with both trauma-related and depression symptoms (OR 16.66, 95% CI 2.89-96.00) and trauma-related symptoms alone (OR 4.59, 95% CI 1.11-18.88) had a higher likelihood of sleep disturbances. Depression symptoms alone were no longer significantly associated with sleep disturbances when analysis was controlled for trauma-related symptoms. Conclusion: Trauma-related symptoms and trauma-related plus moderate to severe depressive symptoms were associated with a higher likelihood of sleep disturbances. Future studies are needed to determine whether psychiatric symptoms are associated with objective changes on polysomnography and actigraphy and whether adequate treatment of psychiatric symptoms can improve sleep disturbances.
The Eight Limbs of Yoga can be Maintained in a Veteran Friendly Yoga Program
(Wolters Kluwer, 2021) Schmid, Arlene A.; Sternke, Elizabeth A.; Do, Ai-Nghia L.; Schalk Conner, Nancy; Starnino, Vincent R.; Davis, Louanne W.; School of Social Work
Background: Posttraumatic stress disorder (PTSD) may occur after a traumatic event and has deleterious effects on individuals, including decreased quality of life and function. Yoga is an intervention that may help with the management of PTSD symptoms, however yoga interventions in research studies frequently only include postures and breathwork, not all eight limbs of yoga. Aims and objectives: The aims of this qualitative study was to examine whether participants with PTSD in a group yoga program discussed the benefits of yoga in a way that represented the eight limbs of yoga, when answering questions about their experience of the yoga program. Methods: Qualitative data were collected after participants completed a 16-week yoga intervention. Qualitative data were collected via survey, reviewed, coded, and categorized into themes representing each of the eight limbs of yoga. Results: Overall, 108 people were randomized to the yoga intervention and 67 individuals completed the intervention and follow up questions used in these analyses. The mean age of the 67 participants in this study was 52.4 years (±12.0), the majority were male (70.2%), and most had combat-related trauma (62.7%). All eight limbs of yoga were represented in the data, including each of the five yamas and niyamas, even though the yoga intervention did not explicitly include Sanskrit terms, definitions, or education about yoga philosophy or the eight limbs of yoga. Conclusion: Results may indicate that yoga, even when only including postures, breathwork, intentions, and relaxation/meditation, may still address all of the yamas, niyamas, and the other eight limbs of yoga.
Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers
(Wiley, 2022-06-29) Weiner, Michael W.; Harvey, Danielle; Landau, Susan M.; Veitch, Dallas P.; Neylan, Thomas C.; Grafman, Jordan H.; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford R., Jr.; Tosun, Duygu; Shaw, Leslie M.; Trojanowski, John Q.; Saykin, Andrew J.; Hayes, Jacqueline; DeCarli, Charles; Alzheimer’s Disease Neuroimaging Initiative; Department of Defense Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
Introduction: Epidemiological studies report an association between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and clinically diagnosed Alzheimer's disease (AD). We examined the association between TBI/PTSD and biomarker-defined AD. Methods: We identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aβ) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years. Results: Exposure groups (TBI, PTSD, and TBI + PTSD) had higher prevalence of mild cognitive impairment (MCI: P < .0001) and worse Mini-Mental State Examination scores (PTSD: P = .008; TBI & PTSD: P = .009) than controls. There were no significant differences in other cognitive scores, MRI volumes, Aβ or tau accumulation, or in most longitudinal measures. Discussion: TBI and/or PTSD were not associated with elevated AD biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.
White Matter Microstructure Is Associated with Serum Neuroactive Steroids and Psychological Functioning
(Mary Ann Liebert, 2023) Umminger, Lisa F.; Rojczyk, Philine; Seitz-Holland, Johanna; Sollmann, Nico; Kaufmann, Elisabeth; Kinzel, Philipp; Zhang, Fan; Kochsiek, Janna; Langhein, Mina; Kim, Cara L.; Wiegand, Tim L. T.; Kilts, Jason D.; Naylor, Jennifer C.; Grant, Gerald A.; Rathi, Yogesh; Coleman, Michael J.; Bouix, Sylvain; Tripodis, Yorghos; Pasternak, Ofer; George, Mark S.; McAllister, Thomas W.; Zafonte, Ross; Stein, Murray B.; O'Donnell, Lauren J.; Marx, Christine E.; Shenton, Martha E.; Koerte, Inga K.; Psychiatry, School of Medicine
Military service members are at increased risk for mental health issues, and comorbidity with mild traumatic brain injury (mTBI) is common. Largely overlapping symptoms between conditions suggest a shared pathophysiology. The present work investigates the associations among white matter microstructure, psychological functioning, and serum neuroactive steroids that are part of the stress-response system. Diffusion-weighted brain imaging was acquired from 163 participants (with and without military affiliation) and free-water-corrected fractional anisotropy (FAT) was extracted. Associations between serum neurosteroid levels of allopregnanolone (ALLO) and pregnenolone (PREGNE), psychological functioning, and whole-brain white matter microstructure were assessed using regression models. Moderation models tested the effect of mTBI and comorbid post-traumatic stress disorder (PTSD) and mTBI on these associations. ALLO is associated with whole-brain white matter FAT (β = 0.24, t = 3.05, p = 0.006). This association is significantly modulated by PTSD+mTBI comorbidity (β = 0.00, t = 2.50, p = 0.027), although an mTBI diagnosis alone did not significantly impact this association (p = 0.088). There was no significant association between PREGNE and FAT (p = 0.380). Importantly, lower FAT is associated with poor psychological functioning (β = -0.19, t = -2.35, p = 0.020). This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning.

Browsing by Subject "Post-traumatic stress disorder"

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