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1.
JMIR Res Protoc ; 13: e55692, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743939

ABSTRACT

BACKGROUND: Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment. OBJECTIVE: This study seeks to develop and investigate a targeted PSA intervention in patients undergoing oncological surgery using a single preoperative VR exposure. The primary objectives are to (1) develop a novel VR program for patients undergoing oncological surgery with general anesthesia; (2) assess the feasibility, including acceptability, of a single exposure to this intervention; (3) assess the feasibility, including acceptability, of outcome measures of PSA; and (4) use these results to refine the VR content and outcome measures for a larger trial. A secondary objective is to preliminarily assess the clinical utility of the intervention for PSA. METHODS: This study comprises 3 phases. Phase 1 (completed) involved the development of a VR prototype targeting PSA, using multidisciplinary iterative input. Phase 2 (data collection completed) involves examining the feasibility aspects of the VR intervention. This randomized feasibility trial involves assessing the novel VR preoperative intervention compared to a VR control (ie, nature trek) condition and a treatment-as-usual group among patients undergoing breast cancer surgery. Phase 3 will involve refining the prototype based on feasibility findings and input from people with lived experience for a future clinical trial, using focus groups with participants from phase 2. RESULTS: This study was funded in March 2019. Phase 1 was completed in April 2020. Phase 2 data collection was completed in January 2024 and data analysis is ongoing. Focus groups were completed in February 2024. Both the feasibility study and focus groups will contribute to further refinement of the initial VR prototype (phase 3), with the final simulation to be completed by mid-2024. CONCLUSIONS: The findings from this work will contribute to the limited body of research examining feasible and broadly accessible interventions for PSA. Knowledge gained from this research will contribute to the final development of a novel VR intervention to be tested in a large population of patients with cancer before surgery in a randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04544618; https://www.clinicaltrials.gov/study/NCT04544618. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55692.


Subject(s)
Anxiety , Feasibility Studies , Neoplasms , Adult , Female , Humans , Male , Middle Aged , Anxiety/prevention & control , Anxiety/therapy , Neoplasms/surgery , Preoperative Care/methods , Psychological Distress , Stress, Psychological , Virtual Reality , Virtual Reality Exposure Therapy/methods , Randomized Controlled Trials as Topic
2.
NeuroRehabilitation ; 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38277308

ABSTRACT

BACKGROUND: The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders. OBJECTIVE: This article reviews the EHVP. METHODS: The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans. RESULTS: This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all. CONCLUSION: Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.

3.
PLoS One ; 19(1): e0296071, 2024.
Article in English | MEDLINE | ID: mdl-38166057

ABSTRACT

BACKGROUND: Psychedelic-assisted therapies hold early promise for treating multiple psychiatric conditions. However, absent standards for the care, teams providing psychedelic-assisted therapy pose a major roadblock to safe administration. Psychedelics often produce spiritually and existentially meaningful experiences, and spiritual health practitioners have been involved in administering psychedelic-assisted therapies in multiple settings, suggesting important qualifications for delivering these therapies. However, the roles and competencies of spiritual health practitioners in psychedelic-assisted therapies have not been described in research. METHOD: This study examined interviews with 15 spiritual health practitioners who have facilitated psychedelic-assisted therapy. Thematic analyses focused on their contributions, application of expertise and professional background, and roles in administering these therapies. RESULTS: Seven themes emerged, comprising two domains: unique and general contributions. Unique contributions included: competency to work with spiritual material, awareness of power dynamics, familiarity with non-ordinary states of consciousness, holding space, and offer a counterbalance to biomedical perspectives. General contributions included use of generalizable therapeutic repertoire when conducting PAT, and contributing to interdisciplinary collaboration. IMPLICATIONS: Spiritual health practitioners bring unique and specific expertise to psychedelic-assisted therapy based on their training and professional experience. They are skilled at interprofessional collaboration in a way that complements other clinical team members. Psychedelic-assisted therapy teams may benefit from including spiritual health practitioners. In order to ensure rigorous standards and quality care, further efforts to delineate the roles and necessary qualifications and training of spiritual health clinicians for psychedelic-assisted therapy are needed.


Subject(s)
Hallucinogens , Hallucinogens/therapeutic use , Quality of Health Care
4.
Curr Top Behav Neurosci ; 64: 335-352, 2023.
Article in English | MEDLINE | ID: mdl-37566312

ABSTRACT

The focus of this chapter is an overview of integrating virtual reality (VR) technology within the context of exposure therapy for anxiety disorders, a gold standard treatment, with a focus on how VR can help facilitate extinction learning processes integral to these interventions. The chapter will include an overview of advantages of incorporating VR within exposure therapy, and benefits specifically within an inhibitory learning approach for extinction training. A review of the empirical literature on the effectiveness of VR exposure therapy for specific phobia and PTSD will be provided, as well as practical overview of how to effectively incorporate VR within exposure therapy.


Subject(s)
Implosive Therapy , Phobic Disorders , Virtual Reality Exposure Therapy , Virtual Reality , Humans , Phobic Disorders/therapy , Anxiety Disorders
5.
JAMA Psychiatry ; 80(7): 743-749, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37256584

ABSTRACT

Importance: Mounting evidence supports the role of spiritual, existential, religious, and theological components in mediating psychedelic-assisted therapy, yet integration of these elements into the clinical setting is lagging. Observations: Although psychedelic-assisted therapy commonly produces spiritually, existentially, religiously, or theologically relevant experiences for patients, these have not been systematically integrated into the psychotherapies that accompany therapeutic uses of psychedelics. As a key feature and potential mediator of therapeutic effects, evidence-based psychedelic-assisted therapies should include these topics in the treatment model. Research across multiple diagnostic targets and treatment contexts suggests that spiritually integrated psychotherapies are effective, feasible, and produce add-on benefits in spiritually, existentially, religiously, and theologically relevant outcomes, which are particularly germane to psychedelics. Established standards in spiritually integrated psychotherapy may be fruitfully applied to psychedelic-assisted therapy. Objectives for spiritually, existentially, religiously, and theologically integrated psychedelic-assisted therapy based on these standards and informed by considerations specific to psychedelics are recommended. Conclusions and Relevance: Spiritual, existential, religious, and theological topics' integration in psychedelic-assisted therapy is needed to ensure culturally competent, evidence-based treatment aligned with the highest standards of clinical care. Neglecting to address these topics can detract from cultural competence, contribute to risks for patients, and potentially undermine treatment success.


Subject(s)
Hallucinogens , Humans , Hallucinogens/pharmacology , Hallucinogens/therapeutic use , Psychotherapy , Treatment Outcome
6.
Mil Med ; 188(11-12): e3356-e3362, 2023 11 03.
Article in English | MEDLINE | ID: mdl-36564939

ABSTRACT

INTRODUCTION: Posttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA. MATERIALS AND METHODS: Twenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT. RESULTS: Before psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P = .014) and interest in PAT (M = 3.67, P = .016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers. CONCLUSIONS: This is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.


Subject(s)
Brain Injuries, Traumatic , Hallucinogens , Military Personnel , Stress Disorders, Post-Traumatic , Veterans , Male , Humans , Female , Veterans/psychology , Hallucinogens/pharmacology , Hallucinogens/therapeutic use , Pilot Projects , Military Personnel/psychology , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/diagnosis
8.
N Engl J Med ; 387(18): 1637-1648, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36322843

ABSTRACT

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).


Subject(s)
Antidepressive Agents , Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Psilocybin , Adult , Humans , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Double-Blind Method , Psilocybin/adverse effects , Psilocybin/therapeutic use , Treatment Outcome , Depressive Disorder, Treatment-Resistant/drug therapy , Depressive Disorder, Treatment-Resistant/psychology
9.
J Psychiatr Res ; 155: 559-566, 2022 11.
Article in English | MEDLINE | ID: mdl-36201968

ABSTRACT

OBJECTIVE: Post-9/11 U.S. veterans and servicemembers are at increased risk for suicide, indicating an important need to identify and mitigate suicidal ideation and behaviors in this population. METHOD: Using data modeling techniques, we examined correlates of suicidal ideation and behavior at intake in 261 Post-9/11 veterans and servicemembers seeking mental health treatment. RESULTS: Our sample endorsed high rates of suicidal ideation and behavior. Approximately 40% of our sample scored in a range on the Suicide Behaviors Questionnaire-Revised (SBQ-R), indicating high clinical risk for suicide. Results from multivariate analyses indicate that greater state and/or trait depression severity, greater anger and anger expression, less impulse control, and lower rank were consistently associated with suicidal ideation and behavior across our models. Negative posttraumatic thoughts about the self, gender, and military branch of service were also significantly associated with suicidal ideation and behavior. CONCLUSIONS: Suicidal ideation and behaviors are common in veterans seeking mental health treatment. State and/or trait depression, anger and impulse control were predictors of increased risk for suicidal ideation and behavior across models. Consistencies and differences across models as well as limitations and practical implications for the findings are discussed.


Subject(s)
Military Personnel , Stress Disorders, Post-Traumatic , Veterans , Humans , Military Personnel/psychology , Risk Factors , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Suicidal Ideation , Veterans/psychology
10.
J Trauma Stress ; 35(5): 1521-1534, 2022 10.
Article in English | MEDLINE | ID: mdl-35776892

ABSTRACT

Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD-related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute mTBI, and structural brain alterations longitudinally in civilian patients (N = 504) who experienced a recent Criterion A traumatic event. Participants who reported loss of consciousness (LOC) were characterized as having mTBI; all others were included in the control group. PTSD symptoms were assessed at enrollment and over the following year; a subset of participants (n = 89) underwent volumetric brain MRI (M = 53 days posttrauma). Classes of PTSD symptom trajectories were modeled using latent growth mixture modeling. Associations between PTSD symptom trajectories and cortical thicknesses or subcortical volumes were assessed using a moderator-based regression. mTBI with LOC during trauma was positively correlated with the likelihood of developing a chronic PTSD symptom trajectory. mTBI showed significant interactions with cortical thickness in the rostral anterior cingulate cortex (rACC) in predicting PTSD symptoms, r = .461-.463. Bilateral rACC thickness positively predicted PTSD symptoms but only among participants who endorsed LOC, p < .001. The results demonstrate positive correlations between mTBI with LOC and PTSD symptom trajectories, and findings related to mTBI with LOC and rACC thickness interactions in predicting subsequent chronic PTSD symptoms suggest the importance of further understanding the role of mTBI in the context of PTSD to inform intervention and risk stratification.


Subject(s)
Brain Concussion , Military Personnel , Stress Disorders, Post-Traumatic , Brain/diagnostic imaging , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Brain Concussion/psychology , Humans , Military Personnel/psychology , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/diagnostic imaging , Stress Disorders, Post-Traumatic/psychology , Unconsciousness/diagnostic imaging , Unconsciousness/etiology , Unconsciousness/psychology
11.
J Psychiatr Res ; 152: 313-320, 2022 08.
Article in English | MEDLINE | ID: mdl-35779388

ABSTRACT

Empirically-supported psychotherapies for posttraumatic stress disorder (PTSD) are highly effective and recommended as first-line treatments, yet dropout rates from standard outpatient therapy are high. Intensive outpatient programs (IOPs) that provide these therapies in condensed format with complementary interventions show promise, as they have demonstrated similar efficacy and higher retention rates. The current study examined initial and long-term outcomes up to 12-months following a 2-week PTSD IOP involving daily prolonged exposure therapy (PE) and adjunctive interventions for veterans and military service members. Participants (N = 376) demonstrated high retention (91%) and large effect size reductions in self-reported PTSD and depression symptoms after two weeks. Small increases in symptoms occurred after 3 months but these stabilized and large reductions compared to baseline were maintained up to 12 months. Piecewise multilevel modeling indicated that demographic variables did not predict PTSD or depression symptom trajectories. Higher PTSD and depression severity at intake predicted higher symptomatology across timepoints and larger relative gains during treatment. Greater alcohol use prior to treatment was associated with higher PTSD symptomatology but did not affect the magnitude of gains. A history of childhood sexual abuse was associated with greater reduction in depression symptoms over treatment, although this effect faded over follow-up. Together these findings underscore the long-term effectiveness of a PE-based IOP across a diverse range of veterans and service members.


Subject(s)
Implosive Therapy , Sex Offenses , Stress Disorders, Post-Traumatic , Veterans , Humans , Outpatients , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/therapy , Treatment Outcome
12.
J Psychopharmacol ; 36(3): 368-377, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35166140

ABSTRACT

BACKGROUND: Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention. AIMS: This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans. METHODS: The study involved a randomized placebo-controlled, two-group, parallel design trial in a sample of healthy adults, age 21-55 recruited from a major metropolitan area. The experimental paradigm included a fear acquisition session followed by an extinction training session 24 hours later, and 2 hours after study drug administration. Fear extinction retention was measured 48 hours after extinction training. Participants (N = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events. RESULTS: Results indicated a significant main effect of session between extinction training and retention with no significant group differences. Significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ2 = 7.29, p = 0.007). CONCLUSION: Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) https://clinicaltrials.gov/ct2/show/NCT03181763?term = MDMA&draw = 2&rank = 9.


Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine , Stress Disorders, Post-Traumatic , Animals , Extinction, Psychological , Fear , Female , Humans , Male , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Reflex, Startle , Stress Disorders, Post-Traumatic/drug therapy
13.
Brain Behav Immun ; 101: 84-92, 2022 03.
Article in English | MEDLINE | ID: mdl-34990746

ABSTRACT

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.


Subject(s)
Stress Disorders, Post-Traumatic , Veterans , Biomarkers , C-Reactive Protein/metabolism , Depression/psychology , Depression/therapy , Humans , Psychotherapy , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology
14.
Psychol Trauma ; 14(5): 862-870, 2022 Jul.
Article in English | MEDLINE | ID: mdl-31971423

ABSTRACT

OBJECTIVE: Advocates of massed prolonged exposure (PE) argue an intensive approach may address between-session distraction, avoidance, and demotivation that can result in dropout or interference with treatment engagement. Despite growing empirical support for the efficacy and effectiveness of massed PE, little evidence suggests massed PE matches patient preferences. Further, program evaluation efforts have not assessed unforeseen or underestimated benefits and drawbacks of massed PE. The current study is the first known study to assess patient reactions to massed PE. METHOD: Participants were 25 military veterans diagnosed with posttraumatic stress disorder who were accepted into a 2-week massed PE program. After the final session, participants completed a written survey using open-ended questions regarding their perceived benefits and drawbacks of massing the full PE protocol into 2 weeks. After demonstrating interrater reliability, coders used a thematic analysis approach to identify themes and subthemes in the qualitative data. RESULTS: Overall, participant reactions were much more positive (51.27%) than negative (17.77%). Participants identified benefits that are largely consistent with the justification for massed PE: (a) The structure limits distractions and avoidance, and (b) quick gains enhance motivation and engagement. With respect to drawbacks, participants identified that massed PE causes short-term discomfort and is demanding in terms of effort and time, which is also consistent with clinical theory of PE and justification for massed delivery. CONCLUSIONS: Participant reactions correspond to the rationale for massed PE; that is, participants identified that despite short-term discomfort and demands, they tend to like and benefit from the intensity of massed PE. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Implosive Therapy , Stress Disorders, Post-Traumatic , Veterans , Humans , Implosive Therapy/methods , Reproducibility of Results , Stress Disorders, Post-Traumatic/therapy
15.
Chronic Stress (Thousand Oaks) ; 5: 24705470211032208, 2021.
Article in English | MEDLINE | ID: mdl-34595364

ABSTRACT

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female (n = 179) and male (n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1 ß , TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma (p = 0.04), had lower pro-inflammatory cytokines and testosterone (p's<0.001), and had higher cortisol and progesterone (p's<0.001) concentrations. Estradiol concentrations were not different between the sexes (p = 0.24). Pro-inflammatory cytokines were a significant mediator in the relationship between sex and probability of developing nonremitting PTSD (p < 0.05), such that men had higher concentrations of pro-inflammatory cytokines which were associated with lower risk of nonremitting PTSD development. This effect was significantly moderated by estradiol (p < 0.05), as higher estradiol levels in men were associated with higher pro-inflammatory cytokine concentrations and lower risk for developing nonremitting PTSD. The current results suggest that sex differences in the pro-inflammatory cytokine response to trauma exposure partially mediate the probability of developing nonremitting PTSD, and that the protective ability to mount an pro-inflammatory cytokine response in men may depend on higher estradiol levels in the aftermath of trauma exposure.

16.
Neuropsychopharmacology ; 46(10): 1811-1820, 2021 09.
Article in English | MEDLINE | ID: mdl-34188182

ABSTRACT

Biomarkers that predict symptom trajectories after trauma can facilitate early detection or intervention for posttraumatic stress disorder (PTSD) and may also advance our understanding of its biology. Here, we aimed to identify trajectory-based biomarkers using blood transcriptomes collected in the immediate aftermath of trauma exposure. Participants were recruited from an Emergency Department in the immediate aftermath of trauma exposure and assessed for PTSD symptoms at baseline, 1, 3, 6, and 12 months. Three empirical symptom trajectories (chronic-PTSD, remitting, and resilient) were identified in 377 individuals based on longitudinal symptoms across four data points (1, 3, 6, and 12 months), using latent growth mixture modeling. Blood transcriptomes were examined for association with longitudinal symptom trajectories, followed by expression quantitative trait locus analysis. GRIN3B and AMOTL1 blood mRNA levels were associated with chronic vs. resilient post-trauma symptom trajectories at a transcriptome-wide significant level (N = 153, FDR-corrected p value = 0.0063 and 0.0253, respectively). We identified four genetic variants that regulate mRNA blood expression levels of GRIN3B. Among these, GRIN3B rs10401454 was associated with PTSD in an independent dataset (N = 3521, p = 0.04). Examination of the BrainCloud and GTEx databases revealed that rs10401454 was associated with brain mRNA expression levels of GRIN3B. While further replication and validation studies are needed, our data suggest that GRIN3B, a glutamate ionotropic receptor NMDA type subunit-3B, may be involved in the manifestation of PTSD. In addition, the blood mRNA level of GRIN3B may be a promising early biomarker for the PTSD manifestation and development.


Subject(s)
Stress Disorders, Post-Traumatic , Biomarkers , Humans , Stress Disorders, Post-Traumatic/genetics , Transcriptome
17.
Mol Psychiatry ; 26(7): 3077-3092, 2021 07.
Article in English | MEDLINE | ID: mdl-33963278

ABSTRACT

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification of novel biological targets to understand mechanisms of pathophysiology and prevention, as well as the determination of patients most at risk who may benefit from immediate intervention. Our study utilizes a novel approach to computationally integrate blood-based transcriptomics, genomics, and interactomics to understand the development of risk vs. resilience in the months following trauma exposure. In a two-site longitudinal, observational prospective study, we assessed over 10,000 individuals and enrolled >700 subjects in the immediate aftermath of trauma (average 5.3 h post-trauma (range 0.5-12 h)) in the Grady Memorial Hospital (Atlanta) and Jackson Memorial Hospital (Miami) emergency departments. RNA expression data and 6-month follow-up data were available for 366 individuals, while genotype, transcriptome, and phenotype data were available for 297 patients. To maximize our power and understanding of genes and pathways that predict risk vs. resilience, we utilized a set-cover approach to capture fluctuations of gene expression of PTSD or depression-converting patients and non-converting trauma-exposed controls to find representative sets of disease-relevant dysregulated genes. We annotated such genes with their corresponding expression quantitative trait loci and applied a variant of a current flow algorithm to identify genes that potentially were causal for the observed dysregulation of disease genes involved in the development of depression and PTSD symptoms after trauma exposure. We obtained a final list of 11 driver causal genes related to MDD symptoms, 13 genes for PTSD symptoms, and 22 genes in PTSD and/or MDD. We observed that these individual or combined disorders shared ESR1, RUNX1, PPARA, and WWOX as driver causal genes, while other genes appeared to be causal driver in the PTSD only or MDD only cases. A number of these identified causal pathways have been previously implicated in the biology or genetics of PTSD and MDD, as well as in preclinical models of amygdala function and fear regulation. Our work provides a promising set of initial pathways that may underlie causal mechanisms in the development of PTSD or MDD in the aftermath of trauma.


Subject(s)
Depressive Disorder, Major , Stress Disorders, Post-Traumatic , Depression , Depressive Disorder, Major/genetics , Genomics , Humans , Prospective Studies , Stress Disorders, Post-Traumatic/genetics , Transcriptome/genetics
18.
Am Psychol ; 76(2): 314-325, 2021.
Article in English | MEDLINE | ID: mdl-33734797

ABSTRACT

Adverse childhood experiences (ACEs) disproportionately impact African Americans because of profound subjection to historical-systemic oppression in addition to personal and intergenerational trauma exposure. This article utilizes a biopsychosocial-cultural framework to understand the correlates of ACE exposure in African Americans and attends to the cultural factors that contribute to resilience. We review the evidence base for culturally informed, preventive-interventions, as well as strategies for bolstering this work by capitalizing on cultural strengths that are salient in the African American community. We also highlight pertinent policy initiatives guided by recent strategic outlines by the Centers for Disease Control and Prevention. These policies provide the backdrop for the recommendations offered to facilitate the healthy biopsychosocial development of individuals and families. These recommendations can contribute to the expansion and creation of new policies that aim to strengthen individual coping in the face of adversity, enhance family bonds and resilience, and promote community capacity to reduce ACE exposure in African Americans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Adverse Childhood Experiences/psychology , Black or African American/psychology , Health Policy , Mental Disorders/prevention & control , Adaptation, Psychological , Female , Humans , Male
19.
Personal Disord ; 12(6): 491-502, 2021 11.
Article in English | MEDLINE | ID: mdl-33444034

ABSTRACT

Posttraumatic stress disorder (PTSD) has a specified precipitant (i.e., trauma), and thus, is particularly well-suited to examine risk and maintenance factors for the development of the disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alternative model of personality disorder (AMPD) is based, in part, on a dimensional trait model; previous research suggests that personality traits are related to PTSD symptoms. To date, there is little research examining this model with regard to PTSD symptoms, and such research could elucidate new strategies for identification and prevention. The present study investigates associations between AMPD traits and PTSD symptoms in a cross-sectional high-risk sample (N = 490; 100% female; 97.8% African American) and in a prospective, longitudinal sample of Level 1 trauma center patients (N = 185; 46.8% female; 72.5% African American). The Personality Inventory for DSM-5 Brief Form domains were significantly associated with PTSD total symptom severity and symptom clusters across both self-report and clinical interview measures. Personality Inventory for DSM-5 Negative Affectivity and Psychoticism emerged as significant predictors of concurrent PTSD. When prospectively predicting PTSD symptoms in the longitudinal cohort, Negative Affectivity and Psychoticism were significant predictors of PTSD symptom severity. These findings indicate how the DSM-5 AMPD pathological traits are associated with risk for stress-related disorders cross-sectionally and prospectively. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Stress Disorders, Post-Traumatic , Black or African American , Cross-Sectional Studies , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Personality Disorders/diagnosis , Prospective Studies , Trauma Centers
20.
J Pers Assess ; 103(2): 204-213, 2021.
Article in English | MEDLINE | ID: mdl-31995393

ABSTRACT

In the current study, we used a sample of predominantly African-American women with high rates of trauma exposure (N = 434) to examine psychometric properties of the Personality Inventory for DSM-5-Brief Form (PID-5-BF). We compared model fit between a model with five correlated latent factors and a higher-order model in which the five latent factors were used to estimate a single "general pathology" factor. Additionally, we computed estimates of internal consistency and domain interrelations and examined indices of convergent/discriminant validity of the PID-5-BF domains by examining their relations to relevant criterion variables. The expected five-factor structure demonstrated good fit indices in a confirmatory factor analysis, and the more parsimonious, higher-order model was retained. Within this higher-order model, the first-order factors accounted for more variance in the criterion variables than the general pathology factor in most instances. The PID-5-BF domains were highly interrelated (rs = .38 to .66), and convergent/discriminant validity of the domains varied: Negative Affectivity and Detachment generally showed the hypothesized pattern of relations with external criteria, while Antagonism and Disinhibition displayed less consistent and discriminant relations. Results are discussed in terms of the costs and benefits of using brief pathological trait measures in samples characterized by high levels of psychopathology.


Subject(s)
Black or African American/psychology , Crime Victims/psychology , Personality Disorders/diagnosis , Personality Inventory/standards , Adult , Diagnostic Tests, Routine , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Problem Behavior , Psychometrics , Reproducibility of Results , Stress, Psychological/diagnosis
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