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1.
Psychol Med ; 54(2): 338-349, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37309917

RESUMO

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.


Assuntos
Cannabis , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Depressão/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/complicações , Psicopatologia
2.
Psychol Med ; : 1-11, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775091

RESUMO

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

3.
Mol Psychiatry ; 28(7): 2975-2984, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36725899

RESUMO

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.


Assuntos
Medo , Transtornos de Estresse Pós-Traumáticos , Humanos , Estudos Longitudinais , Medo/fisiologia , Tonsila do Cerebelo , Giro do Cíngulo/patologia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/patologia
4.
Mol Psychiatry ; 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932158

RESUMO

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

5.
J Neurosci ; 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879096

RESUMO

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

6.
Psychol Med ; 53(11): 4952-4961, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35775366

RESUMO

BACKGROUND: Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS. METHODS: Self-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale - Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample). RESULTS: Twenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms. CONCLUSIONS: These analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Dor
7.
Ann Emerg Med ; 81(3): 249-261, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36328855

RESUMO

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Serviço Hospitalar de Emergência , Acidentes de Trânsito , Veículos Automotores
8.
Psychol Med ; 52(10): 1934-1947, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33118917

RESUMO

BACKGROUND: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. METHODS: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. RESULTS: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. CONCLUSIONS: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Depressão/epidemiologia , Estudos Longitudinais , Acidentes de Trânsito/psicologia , Prevalência , Veículos Automotores
9.
Mol Psychiatry ; 26(7): 3108-3121, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33077855

RESUMO

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Acidentes de Trânsito , Feminino , Humanos , Estudos Longitudinais , Veículos Automotores , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia
10.
Depress Anxiety ; 39(1): 56-70, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34783142

RESUMO

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting posttraumatic preventive interventions. METHODS: Data come from 1306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the advancing understanding of recovery after trauma study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative risk = 2.6-7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2- and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as the higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2 and 8 weeks could help target early interventions for psychopathological reactions to MVCs.


Assuntos
Transtorno Depressivo Maior , Transtornos de Estresse Pós-Traumáticos , Acidentes de Trânsito , Depressão , Transtorno Depressivo Maior/epidemiologia , Humanos , Veículos Automotores , Transtornos de Estresse Pós-Traumáticos/epidemiologia
11.
Pharmacogenet Genomics ; 30(9): 201-207, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33017130

RESUMO

OBJECTIVES: The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pediatric bronchodilator response (BDR) during acute asthma exacerbations. METHODS: This is an exploratory pilot study that collected buccal swabs for DNA and measured BDR during ED encounters for pediatric asthma exacerbations. We evaluated the study's feasibility with a qualitative analysis of ED provider surveys and quantitatively by the proportion of eligible patients enrolled. RESULTS: We enrolled 59 out of 90 patients (65%) that were identified and considered eligible during a 5-month period (target enrollment 60 patients over 12 months). The median patient age was 7 years (interquartile range 4-9 years), 61% (N = 36) were male, and 92% (N = 54) were African American. Quality DNA collection was successful for all 59 patients. The ED provider survey response rate was 100%. Most ED providers reported that the study did not impact their workflow (98% of physicians, 88% of nurses, and 90% of respiratory therapists). ED providers did report difficulties with spirometry in the younger age group. CONCLUSIONS: Pharmacogenomic studies can be conducted in the ED setting, and enroll a younger patient population with a high proportion of minority participants. By disseminating this study's methods and feasibility analysis, we aim to increase interest in pharmacogenomic studies set in the ED and aimed toward future ED-based pharmacogenomic decision-making.


Assuntos
Asma/tratamento farmacológico , Asma/genética , Atenção à Saúde/normas , Serviço Hospitalar de Emergência/normas , Implementação de Plano de Saúde/métodos , Testes Farmacogenômicos/métodos , Médicos/normas , Adolescente , Asma/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Projetos Piloto , Guias de Prática Clínica como Assunto/normas , Prognóstico , Inquéritos e Questionários
12.
Ann Emerg Med ; 76(3): 280-290, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32828327

RESUMO

STUDY OBJECTIVE: Emergency department (ED) visits provide an important opportunity for elder abuse identification. Our objective was to assess the accuracy of the ED Senior Abuse Identification (ED Senior AID) tool for the identification of elder abuse. METHODS: We conducted a study of the ED Senior AID tool in 3 US EDs. Participants were English-speaking patients 65 years old and older who provided consent or for whom a legally authorized representative provided consent. Research nurses administered the screening tool, which includes a brief mental status assessment, questions about elder abuse, and a physical examination for patients who lack the ability to report abuse or for whom the presence or absence of abuse was uncertain. The reference standard was based on the majority opinion of a longitudinal, expert, all data (LEAD) panel following review and discussion of medical records, clinical social worker notes, and a structured social and behavioral evaluation. For the reference standard, LEAD panel members were blinded to the results of the screening tool. RESULTS: Of 916 enrolled patients, 33 (3.6%) screened positive for elder abuse. The LEAD panel reviewed 125 cases: all 33 with positive screen results and a 10% random sample of negative screen results. Of these, the panel identified 17 cases as positive for elder abuse, including 16 of the 33 cases that screened positive. The ED Senior AID tool had a sensitivity of 94.1% (95% confidence interval [CI] 71.3% to 99.9%) and specificity of 84.3% (95% CI 76.0% to 90.6%). CONCLUSION: This multicenter study found the ED Senior AID tool to have a high sensitivity and specificity as a screening tool for elder abuse, albeit with wide CIs.


Assuntos
Abuso de Idosos/diagnóstico , Avaliação Geriátrica , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Serviços de Saúde para Idosos , Humanos , Masculino , Sensibilidade e Especificidade , Estados Unidos
13.
Air Med J ; 39(1): 44-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32044068

RESUMO

INTRODUCTION: Pediatric air transport research is limited, especially scene transport. Study purpose was to review transport epidemiology, outcomes, and documentation to inform development of a pediatric flight quality improvement (QI) program and outreach. METHODS: Study design was ongoing review and analysis of flight, ED, EMS and hospital records over 2 years from children ≤ 18 years transported by a regional flight program. Mission type included trauma, medical, scene and interfacility. Records were reviewed monthly by a pediatric medical director (PMD) with ongoing QI and educational initiatives. Peer review was added in year two. Demographic and outcome variables included weight, times, procedures, pain scales, Glasgow Coma Scale (GCS), medications, disposition, etc. Two QI focus areas were studied using QI Macros®: weight and pain documentation. RESULTS: Children accounted for 8% of total flights (165/2076). Transport was 58% scene; 42% interfacility. Median dispatch to arrival time was 21 minutes. Saturday accounted for 24% of flights. Mean scene GCS was 12; 39 (24%) patients were intubated. Scene weight in kilograms improved 18% and pain documentation improved from 49% to 79% during the study. CONCLUSION: Addition of PMD, peer and outcome review processes provided opportunities for improving pediatric transport QI initiatives and targeted outreach education.


Assuntos
Resgate Aéreo/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Serviços Médicos de Emergência/normas , Pediatria/estatística & dados numéricos , Pediatria/normas , Guias de Prática Clínica como Assunto , Melhoria de Qualidade/normas , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade/estatística & dados numéricos , Estudos Retrospectivos
14.
J Neurosci ; 38(39): 8407-8420, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30150364

RESUMO

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene-miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies.SIGNIFICANCE STATEMENTFKBP5 is a critical regulator of the stress response. Previous studies have shown that dysregulation of the expression of this gene plays a role in the pathogenesis of chronic pain development as well as a number of comorbid neuropsychiatric disorders. In the current study, we identified a functional allele (rs3800373) in the 3'UTR of FKBP5 that influences vulnerability to chronic post-traumatic pain in two ethnic cohorts. Using multiple complementary experimental approaches, we show that the FKBP5 rs3800373 minor allele alters the secondary structure of FKBP5 mRNA, decreasing the binding of a stress- and pain-associated microRNA, miR-320a. This results in relatively greater FKBP5 translation, unchecked by miR-320a, increasing glucocorticoid resistance and increasing vulnerability to post-traumatic pain.


Assuntos
Dor Crônica/genética , MicroRNAs/genética , Dor Musculoesquelética/genética , Proteínas de Ligação a Tacrolimo/genética , Regiões 3' não Traduzidas , Adulto , Negro ou Afro-Americano/genética , Alelos , Dor Crônica/metabolismo , Feminino , Genótipo , Humanos , Masculino , MicroRNAs/metabolismo , Dor Musculoesquelética/metabolismo , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estrutura Secundária de Proteína , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , População Branca/genética , Adulto Jovem
15.
Am J Med Genet B Neuropsychiatr Genet ; 180(6): 415-427, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30537437

RESUMO

Co-morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision, are associated with greater disability than either outcome alone, and are more prevalent in women than men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0-10 numeric rating scale) and PTSS (impact of events scale, revised) outcomes were assessed 6 months following motor vehicle collision. Blood RNA were sequenced (n = 101) and the relationship between X chromosome mRNA expression levels and co-morbid CMSP and PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic X chromosome mRNA predicting CMSP and PTSS in women were genes previously found to escape X chromosome inactivation (11/40, z = -2.9, p = .004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of X chromosome inactivation, X-inactive specific transcript (XIST) and Yin Yang 1 (YY1), was different in women developing CMSP and PTSS. Together, these data suggest that X chromosome genes that escape inactivation may contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision.


Assuntos
Dor Musculoesquelética/genética , Transtornos de Estresse Pós-Traumáticos/genética , Inativação do Cromossomo X/genética , Acidentes de Trânsito/psicologia , Adulto , Negro ou Afro-Americano , Cromossomos Humanos X/genética , Cromossomos Humanos X/fisiologia , Comorbidade , Feminino , Regulação da Expressão Gênica/genética , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Prevalência , Inativação do Cromossomo X/fisiologia
16.
Am J Geriatr Psychiatry ; 25(9): 953-963, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28506605

RESUMO

OBJECTIVE: To characterize risk factors for and consequences of post-traumatic stress disorder (PTSD) among older adults evaluated in the emergency department (ED) following motor vehicle collision (MVC). DESIGN: Prospective multicenter longitudinal study (2011-2015). SETTING: 9 EDs across the United States. PARTICIPANTS: Adults aged 65 years and older who presented to an ED after MVC without severe injuries. MEASUREMENTS: PTSD symptoms were assessed 6 months after the ED visit using the Impact of Event Scale-Revised. RESULTS: Of 223 patients, clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%-26%). PTSD symptoms were more common in patients who did not have a college degree, had depressive symptoms prior to the MVC, perceived the MVC as life-threatening, had severe ED pain, and expected their physical or emotional recovery time to be greater than 30 days. Three factors (ED pain severity [0-10 scale], perceived life-threatening MVC [0-10 scale], and pre-MVC depressive symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with an area under the curve of 0.76. Compared to patients without PTSD symptoms, those with PTSD symptoms were at higher risk for persistent pain (72% versus 30%), functional decline (67% versus 42%), and new disability (49% versus 18%). CONCLUSIONS: Among older adults treated in the ED following MVC, clinically significant PTSD symptoms at 6 months were present in 21% of patients and were associated with adverse health outcomes. Increased risk for PTSD development can be identified with moderate accuracy using information readily available in the ED.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Envelhecimento , Atitude Frente a Saúde , Depressão/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Dor/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Acidentes de Trânsito/psicologia , Idoso , Envelhecimento/psicologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Dor/etiologia , Dor/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia
17.
Pediatr Emerg Care ; 33(11): e134-e136, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095782

RESUMO

Infantile myofibromatosis is a disorder of mesenchymal tumors that usually presents within the first 2 years of life. Most patients initially present because of the presence of visible or palpable subcutaneous tumors. We report a case of a fussy 5-week-old infant who presented to an emergency department with bilateral femur fractures initially thought to be due to nonaccidental trauma or a metabolic bone disorder. She was ultimately diagnosed after admission with infantile myofibromatosis after taking an extensive family history and after further laboratory and radiologic evaluation. There are no previously published cases of undiagnosed infantile myofibromatosis presenting to the emergency department, especially with multiple long bone fractures.


Assuntos
Fraturas Múltiplas/etiologia , Miofibromatose/congênito , Diagnóstico Diferencial , Tratamento Farmacológico/métodos , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Miofibromatose/complicações , Miofibromatose/diagnóstico , Miofibromatose/tratamento farmacológico
18.
Psychosom Med ; 78(1): 68-78, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26588823

RESUMO

OBJECTIVES: To determine the influence of epidemiologic factors and the influence of genetic variants affecting FKBP5, a protein known to modulate hypothalamic-pituitary-adrenocortical axis function, on the severity of somatic symptoms commonly termed "postconcussive" 6 and 12 months after motor vehicle collision (MVC). METHODS: European Americans 18 to 65 years of age who presented to one of eight emergency departments (EDs) after MVC were enrolled. Exclusion criteria included hospital admission. Blood samples were collected in the ED for genotyping. Participants completed evaluations including an adapted Rivermead Post-Concussive Symptoms Questionnaire in the ED and at 6 weeks, 6 months, and 1 year. Repeated-measures analysis of covariance was used to evaluate the association between epidemiologic factors (sociodemographic, pre-MVC health, collision characteristics, head injury, peritraumatic pain, and stress), FKBP5 genetic variants, and postconcussive symptom severity. RESULTS: Among 943 patients recruited in the ED, follow-up was completed on 835 (88%) at 6 months and 857 (90%) at 1 year. Self-reported head impact during collision was not associated with chronic postconcussive symptom severity. After correction for multiple testing, three FKBP5 single-nucleotide polymorphisms (rs3800373, rs7753746, and rs9380526) predicted chronic postconcussive symptom severity, with an average symptom severity of 1.10 (95% confidence interval = 0.96-1.24), 1.36 (1.21-1.51), and 1.55 (1.23-1.88) for one, two, or three copies of minor allele at rs3800373 (p = .001). Similar effect sizes were observed for the minor alleles of rs7753746 and rs9380526. CONCLUSIONS: Postconcussive symptoms after minor MVC are not generally related to the severity of mild brain injury. This study shows that neurobiologic stress systems may play a role in the pathogenesis of postconcussive symptoms.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Polimorfismo de Nucleotídeo Único , Síndrome Pós-Concussão/genética , Proteínas de Ligação a Tacrolimo/genética , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Serviço Hospitalar de Emergência , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Síndrome Pós-Concussão/epidemiologia , Síndrome Pós-Concussão/fisiopatologia , Síndrome Pós-Concussão/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Proteínas de Ligação a Tacrolimo/sangue , Adulto Jovem
19.
Ann Emerg Med ; 67(2): 166-176.e1, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26092559

RESUMO

STUDY OBJECTIVE: Motor vehicle crashes are the second most common form of trauma among older adults. We seek to describe the incidence, risk factors, and consequences of persistent pain among older adults evaluated in the emergency department (ED) after a motor vehicle crash. METHODS: We conducted a prospective longitudinal study of patients aged 65 years or older who presented to one of 8 EDs after motor vehicle crash between June 2011 and June 2014 and were discharged home after evaluation. ED evaluation was done through in-person interview; follow-up data were obtained through mail-in survey or telephone call. Pain severity (0 to 10 scale) overall and for 15 parts of the body were assessed at each follow-up point. Principal component analysis was used to assess the dimensionality of the locations of pain data. Participants reporting pain severity greater than or equal to 4 attributed to the motor vehicle crash at 6 months were defined as having persistent pain. RESULTS: Of the 161 participants, 72% reported moderate to severe pain at the ED evaluation. At 6 months, 26% of participants reported moderate to severe motor vehicle crash-related pain. ED characteristics associated with persistent pain included acute pain severity; pain located in the head, neck, and jaw or lower back and legs; poor self-rated health; less formal education; pre-motor vehicle crash depressive symptoms; and patient's expected time to physical recovery more than 30 days. Compared with individuals without persistent pain, those with persistent pain were substantially more likely at 6-month follow-up to have also experienced a decline in their capacity for physical function (73% versus 36%; difference=37%; 95% confidence interval [CI] 19% to 52%), a new difficulty with activities of daily living (42% versus 17%; difference=26%; 95% CI 10% to 43%), a 1-point or more reduction in overall self-rated health on a 5-point scale (54% versus 30%; difference=24%; 95% CI 6% to 41%), and a change in their living situation to obtain additional help (23% versus 8%; difference=15%; 95% CI 2% to 31%). CONCLUSION: Among older adults discharged home from the ED post-evaluation after a motor vehicle crash, persistent pain is common and frequently associated with functional decline and disability.


Assuntos
Acidentes de Trânsito , Dor/epidemiologia , Dor/etiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Serviço Hospitalar de Emergência , Feminino , Avaliação Geriátrica , Humanos , Incidência , Escala de Gravidade do Ferimento , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Medição da Dor , Alta do Paciente , Estudos Prospectivos , Fatores de Risco
20.
BMC Geriatr ; 16: 86, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27094038

RESUMO

BACKGROUND: Restricted physical activity commonly occurs following acute musculoskeletal pain in older adults and may influence long-term outcomes. We sought to examine the relationship between restricted physical activity after motor vehicle collision (MVC) and the development of persistent pain. METHODS: We examined data from a prospective study of adults ≥65 years of age presenting to the emergency department (ED) after MVC without life-threatening injuries. Restricted physical activity 6 weeks after MVC was defined in three different ways: 1) by a ≥25 point decrease in Physical Activity Scale in the Elderly (PASE) score, 2) by the answer "yes" to the question, "during the past two weeks, have you stayed in bed for at least half a day?", and 3) by the answer "yes" to the question, "during the past two weeks, have you cut down on your usual activities as compared to before the accident?" We examined relationships between each definition of restricted activity and pain severity, pain interference, and functional capacity at 6 months with adjustment for confounders. RESULTS: Within the study sample (N = 164), adjusted average pain severity scores at 6 months did not differ between patients with and without restricted physical activity based on decreased PASE score (2.54 vs. 2.07, p = 0.32). In contrast, clinically and statistically important differences in adjusted average pain severity at 6 months were observed for patients who reported spending half a day in bed vs. those who did not (3.56 vs. 1.91, p < 0.01). In adjusted analyses, both decreased PASE score and cutting down on activity were associated with functional capacity at 6 months, but only decreased PASE score was associated with increased ADL difficulty at 6 months (0.70 vs. -0.01, p = 0.02). CONCLUSIONS: Among older adults experiencing MVC, those reporting bed rest or reduced activity 6 weeks after the collision reported higher pain and pain interference scores at 6 months. More research is needed to determine if interventions to promote activity can improve outcomes after MVC in older adults.


Assuntos
Acidentes de Trânsito/tendências , Limitação da Mobilidade , Atividade Motora , Veículos Automotores , Medição da Dor/tendências , Dor/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Serviço Hospitalar de Emergência/tendências , Feminino , Humanos , Estudos Longitudinais , Masculino , Atividade Motora/fisiologia , Dor/epidemiologia , Medição da Dor/métodos , Estudos Prospectivos
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