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Almost three decades have passed since the first posttraumatic stress disorder (PTSD) neuroimaging study was published. Since then, the field of clinical neuroscience has made advancements in understanding the neural correlates of PTSD to create more efficacious treatment strategies. While gold-standard psychotherapy options are available, many patients do not respond to them, prematurely drop out, or never initiate treatment. Therefore, elucidating the neurobiological mechanisms that define the disorder can help guide clinician decision-making and develop individualized mechanisms-based treatment options. To this end, this narrative review highlights progress made in the last decade in adult and youth samples on three outstanding questions in PTSD research: (1) Which neural alterations serve as predisposing (pre-exposure) risk factors for PTSD development, and which are acquired (post-exposure) alterations? (2) Which neural alterations can predict treatment outcomes and define clinical improvement? and (3) Can neuroimaging measures be used to define brain-based biotypes of PTSD? While the studies highlighted in this review have made progress in answering the three questions, the field still has much to do before implementing these findings into clinical practice. Overall, to better answer these questions, we suggest that future neuroimaging studies of PTSD should (A) utilize prospective longitudinal designs, collecting brain measures before experiencing trauma and at multiple follow-up time points post-trauma, taking advantage of multi-site collaborations/consortiums; (B) collect two scans to explore changes in brain alterations from pre-to-post treatment and compare changes in neural activation between treatment groups, including longitudinal follow up assessments; and (C) replicate brain-based biotypes of PTSD. By synthesizing recent findings, this narrative review will pave the way for personalized treatment approaches grounded in neurobiological evidence.
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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.
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Cannabis , Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Humanos , Femenino , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/diagnóstico , Depresión/diagnóstico , Trastornos Relacionados con Sustancias/complicaciones , PsicopatologíaRESUMEN
Background: Although alcohol and nicotine are often used together, the biological consequences of these substances are not well understood. Identifying shared targets will inform cessation pharmacotherapies and provide a deeper understanding of how co-use of alcohol and nicotine impacts health, including biomarkers of stress and inflammation.Objective: We examined the effects of nicotine exposure and withdrawal on alcohol self-administration (SA), stress and inflammatory biomarkers, and a G-protein coupled receptor subunit (Gß) in brain areas associated with drug use.Methods: Male rats were trained to SA alcohol and then received a nicotine pump (n = 7-8 per group). We assessed alcohol intake for 12 days during nicotine exposure and then following pump removal to elicit withdrawal. After the behavioral studies, we assessed plasma leptin, corticosterone, and interleukin-1ß (IL-1ß), and Gß protein expression in the amygdala, nucleus accumbens (NAc), and prefrontal cortex (PFC).Results: Nicotine exposure or withdrawal did not alter alcohol intake (p > .05). Alcohol and nicotine withdrawal elevated corticosterone levels (p = .015) and decreased Gß levels in the PFC (p = .004). In the absence of nicotine, alcohol SA suppressed IL-1ß levels (p = .039). Chronic exposure to nicotine or withdrawal during alcohol SA did not alter leptin levels or Gß expression in the amygdala or NAc (p's > .05).Conclusions: The combination of alcohol SA and nicotine withdrawal produced a persistent increase in stress biomarkers and a suppression in Gß expression in the PFC, providing an important first step toward understanding the common biological mechanisms of alcohol/nicotine misuse.
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Nicotina , Síndrome de Abstinencia a Sustancias , Ratas , Masculino , Animales , Nicotina/efectos adversos , Leptina/metabolismo , Leptina/farmacología , Leptina/uso terapéutico , Corticosterona/metabolismo , Corticosterona/farmacología , Corticosterona/uso terapéutico , Ratas Wistar , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Corteza Prefrontal , Etanol/efectos adversosRESUMEN
Experiencing racism is linked to lower subjective social status (SSS), defined as one's perception of their position in society. SSS is influenced by power, prestige, and objective socioeconomic status (SES). Previous findings suggest that race-related stress may be related to adverse mental health outcomes through SSS in Black Americans, a population that has been deeply affected by continuing legacies of oppression. The current study examines the indirect association between race-related stress and posttraumatic stress disorder (PTSD) and depression symptoms through SSS in a community sample of largely trauma-exposed Black Americans (N = 173). Hierarchical regression analyses indicated that overall race-related stress significantly predicted lower SSS, higher PTSD symptoms, and higher depression symptoms. Analyses also revealed indirect effects of cultural race-related stress on PTSD and depression symptoms through SSS after controlling for SES. Results suggest that the experience of race-related stress, particularly cultural race-related stress, which involves the degradation and disparagement of one's culture and worldview, is associated with more severe PTSD and depression symptoms potentially due to these experiences decreasing Black Americans' SSS. Findings support the need for systemic intervention strategies to disrupt the cultural oppression of Black Americans and improve the societal value and mental health of this population.
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Depresión , Estatus Social , Trastornos por Estrés Postraumático , Estrés Psicológico , Humanos , Negro o Afroamericano , Depresión/epidemiología , Racismo , Clase Social , Trastornos por Estrés Postraumático/epidemiología , Estrés Psicológico/epidemiología , Trauma Psicológico/epidemiologíaRESUMEN
PURPOSE: The aim of this study was to assess if long-term supplementation of omega-3 fatty acids or a diet rich in omega-6 fatty acids ameliorates disease severity in a murine model of pneumococcal pneumonia. We hypothesize that long-term dietary supplementation of omega-3 fatty acids will reduce inflammation, disease severity and improve survival compared to omega-6 fatty acids. METHODS: Mice receiving diets supplemented with Omega-3 or Omega-6 for two months were intranasally infected with Streptococcus pneumoniae. We analyzed survival, bacterial burden, histopathology and inflammatory biomarkers. RESULTS: Our results showed that Omega-3 supplementation had increased survival (p = 0.005), less bacteremia (p = 0.0001) and lower bacterial burden in the lungs (p = 0.0002) when compared to the Omega-6 supplementation. Overall, Omega-3 reduced lung pathology, in particular peribronchial inflammation and cell death. Analyses of lung homogenates showed the Omega-3 cohort had decreased levels of the inflammatory cytokine interleukin-6 and an increase in anti-inflammatory cytokine interleukin-10. CONCLUSIONS: Supplementation of mouse diets with Omega-3 fatty acids improved survival, bacterial invasion in the blood and lungs as well as decreased overall lung tissue inflammation and cell death when compared to the Omega-6 supplemented diets. Translation of these findings in humans may improve outcomes of patients at risk for pneumonia.
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Antiinflamatorios/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Alimentación Animal , Animales , Carga Bacteriana , Suplementos Dietéticos , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/patología , Ratones , Mortalidad , Neumonía Neumocócica/tratamiento farmacológico , Neumonía Neumocócica/mortalidad , Neumonía Neumocócica/patología , Resultado del TratamientoRESUMEN
RATIONALE: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. OBJECTIVES: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. METHODS: We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. MEASUREMENTS AND MAIN RESULTS: Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P < 0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. CONCLUSIONS: S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in an NHP model of severe pneumonia.
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Cardiotoxicidad/etiología , Miocardio/patología , Neumonía Neumocócica/complicaciones , Streptococcus pneumoniae/patogenicidad , Animales , Antibacterianos/uso terapéutico , Western Blotting , Cardiotoxicidad/sangre , Modelos Animales de Enfermedad , Ecocardiografía , Electrocardiografía , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Corazón/microbiología , Masculino , Papio , Neumonía Neumocócica/sangre , Neumonía Neumocócica/tratamiento farmacológico , Troponina T/sangreRESUMEN
Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1ß in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention.
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Toxinas Bacterianas/toxicidad , Macrófagos Alveolares/microbiología , Neumonía Bacteriana/metabolismo , Neumonía Bacteriana/patología , Proteínas Citotóxicas Formadoras de Poros/toxicidad , Animales , Apoptosis/fisiología , Western Blotting , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Ratones , Ratones Noqueados , Necrosis , Proteínas Quinasas/metabolismo , ARN Interferente Pequeño , Especies Reactivas de OxígenoRESUMEN
Streptococcus pneumoniae is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that S. pneumoniae mutants deficient in NanA and ß-galactosidase A (BgaA) failed to form biofilms in vivo despite normal biofilm-forming abilities in vitro Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation in vivo Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role.
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Biopelículas/crecimiento & desarrollo , Metabolismo de los Hidratos de Carbono/fisiología , Carbohidratos/farmacología , Galactosa/farmacocinética , Neuraminidasa/fisiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/fisiología , Análisis de Varianza , Animales , Biopelículas/efectos de los fármacos , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Femenino , Galactosa/metabolismo , Galactosa/farmacología , Humanos , Ratones , Ratones Endogámicos BALB C , Ácido N-Acetilneuramínico/metabolismo , Líquido del Lavado Nasal/química , Tabique Nasal/metabolismo , Tabique Nasal/microbiología , Nasofaringe/metabolismo , Nasofaringe/microbiología , Neuraminidasa/metabolismo , Infecciones Neumocócicas/metabolismo , Streptococcus pneumoniae/efectos de los fármacos , beta-Galactosidasa/deficiencia , beta-Galactosidasa/metabolismoRESUMEN
OBJECTIVE: To determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. DESIGN: This study was a secondary data analysis of a prospective cohort study. SETTING: Patients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. PATIENTS: Patients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. INTERVENTIONS: None. MEASUREMENTS: Baseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72h of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (⩾2 organ dysfunction) and in-hospital mortality, respectively. MAIN RESULTS: Forty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. CONCLUSIONS: High levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality.
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Mortalidad Hospitalaria , Molécula 1 de Adhesión Intercelular/sangre , Insuficiencia Multiorgánica , Sepsis , Molécula 1 de Adhesión Celular Vascular/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/mortalidad , Sepsis/sangre , Sepsis/mortalidad , Índice de Severidad de la Enfermedad , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
Serratia marcescens, a member of the carbapenem-resistant Enterobacteriaceae, is an important emerging pathogen that causes a wide variety of nosocomial infections, spreads rapidly within hospitals, and has a systemic mortality rate of ≤41%. Despite multiple clinical descriptions of S. marcescens nosocomial pneumonia, little is known regarding the mechanisms of bacterial pathogenesis and the host immune response. To address this gap, we developed an oropharyngeal aspiration model of lethal and sublethal S. marcescens pneumonia in BALB/c mice and extensively characterized the latter. Lethal challenge (>4.0 × 10(6) CFU) was characterized by fulminate hemorrhagic pneumonia with rapid loss of lung function and death. Mice challenged with a sublethal dose (<2.0 × 10(6) CFU) rapidly lost weight, had diminished lung compliance, experienced lung hemorrhage, and responded to the infection with extensive neutrophil infiltration and histopathological changes in tissue architecture. Neutrophil extracellular trap formation and the expression of inflammatory cytokines occurred early after infection. Mice depleted of neutrophils were exquisitely susceptible to an otherwise nonlethal inoculum, thereby demonstrating the requirement for neutrophils in host protection. Mutation of the genes encoding the cytolysin ShlA and its transporter ShlB resulted in attenuated S. marcescens strains that failed to cause profound weight loss, extended illness, hemorrhage, and prolonged lung pathology in mice. This study describes a model of S. marcescens pneumonia that mimics known clinical features of human illness, identifies neutrophils and the toxin ShlA as a key factors important for defense and infection, respectively, and provides a solid foundation for future studies of novel therapeutics for this important opportunistic pathogen.
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Proteínas Bacterianas/genética , Proteínas Hemolisinas/genética , Neumonía/patología , Infecciones por Serratia/inmunología , Serratia marcescens/inmunología , Animales , Líquido del Lavado Bronquioalveolar/citología , Infección Hospitalaria , Citocinas/biosíntesis , Citocinas/inmunología , Modelos Animales de Enfermedad , Femenino , Hemorragia/microbiología , Hemorragia/patología , Inflamación/inmunología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Neumonía/inmunología , Neumonía/microbiología , Neumonía/mortalidad , Infecciones por Serratia/microbiología , Infecciones por Serratia/mortalidad , Serratia marcescens/patogenicidadRESUMEN
CONTEXT: Chromogranin A (CgA) is a novel biomarker with potential to assess mortality risk of patients with severe sepsis. OBJECTIVE: Assess association of CgA levels and mortality risk of severely septic patients. METHODS: Serum CgA levels were measured in 50 hospitalized, severely septic patients with organ failure <48 h. RESULTS: Higher CgA levels trended toward higher ICU and hospital mortality. Patients without cardiovascular disease who died in the ICU had higher median (IQR) CgA levels 602.3 (343.3, 1134.3) ng/ml versus 205.5 (130.7, 325.9) ng/ml, p = 0.01. CONCLUSIONS: High CgA levels predict ICU mortality in severely septic patients without prior cardiovascular disease.
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Cromogranina A/sangre , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/mortalidad , Sepsis/diagnóstico , Sepsis/mortalidad , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/patología , Pronóstico , Sepsis/sangre , Sepsis/patología , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Black pregnant individuals are at disproportionate risk for posttraumatic stress disorder (PTSD) compared to other groups. A wealth of literature suggests racial stress contributes to this inequity, but cultural and structural mechanisms, such as perceived barriers to mental health treatment, underlying the relationship between racial stress and PTSD symptoms remain understudied. Negative evaluations of psychotherapy and stigma represent potential mechanisms, though no previous studies have examined these associations. To address this gap, we tested an indirect effect of racial stress on PTSD symptoms through perceived barriers to mental health treatment in pregnant Black individuals. METHOD: Mediation analyses were used to assess an indirect relationship between racial stress and PTSD symptoms through perceived barriers to mental health treatment. RESULTS: At the bivariate level, racial stress was significantly associated with PTSD symptoms (r = .20, p = .03) and negative evaluations of therapy (r = .22, p = .02), but not with stigma (r = .140, p = .147). Negative evaluations of therapy were also associated with PTSD symptoms (r = .43, p < .001). There was an indirect effect of racial stress on PTSD symptoms through a negative evaluation of therapy, ß = .08, SE = 0.04, CI [0.01, 0.18]. More specifically, racial stress was associated with a more negative evaluation of therapy, which was in turn associated with more PTSD symptoms. CONCLUSIONS: Results highlight the need for accessible and culturally competent mental health care for pregnant Black individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Mujeres Embarazadas , Racismo , Trastornos por Estrés Postraumático , Femenino , Humanos , Embarazo , Negro o Afroamericano , Psicoterapia , Grupos Raciales , Trastornos por Estrés Postraumático/psicología , Racismo/psicología , Mujeres Embarazadas/psicologíaRESUMEN
Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.
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Black pregnant and postpartum individuals are at risk for intimate partner violence (IPV), and those with a history of childhood maltreatment and IPV are even more likely to be re-victimized during pregnancy. However, it is unknown if specific types of child maltreatment predict later IPV with and without a weapon better than others. The current study sought to (i) document the prevalence of childhood maltreatment and IPV and (ii) examine the relations among types of childhood maltreatment and later IPV with and without a weapon within a sample of Black individuals seeking prenatal care at a large public hospital in the southeastern United States. Participants (n = 186; mean age = 27.2 years, SD = 5.3) completed measures assessing childhood maltreatment and IPV with and without a weapon. Approximately 68.5% of participants (n = 124) endorsed experiencing childhood maltreatment, while 42.6% (n = 78) endorsed experiencing IPV. The bivariate relations among five childhood maltreatment types (i.e., sexual, physical, and emotional abuse, physical and emotional neglect) and IPV with and without a weapon were assessed. All childhood maltreatment subtype scores-except childhood physical neglect-were significantly higher among participants who reported a history of IPV with or without a weapon compared to participants who denied a history of IPV with or without a weapon. Logistic regression models revealed childhood sexual abuse emerged as the only significant predictor of experiencing IPV with a weapon (B = 0.10, p = .003) and IPV without a weapon (B = 0.11, p = .001). For every point increase in childhood sexual abuse subtype score, the odds of experiencing IPV with and without a weapon increased by 10% (OR = 1.10, 95%CI [1.04, 1.18]) and 12% (OR = 1.12, [1.05, 1.20]), respectively. Findings suggest that screening for childhood sexual abuse may provide a critical opportunity for maternity care providers to identify individuals at increased risk for IPV victimization with and without a weapon.
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Posttraumatic Stress Disorder (PTSD) is a heterogeneous mental health disorder that occurs following traumatic experience. Understanding its neurobiological basis is crucial to advance early diagnosis and treatment. Electroencephalography (EEG) can be used to explore the neurobiological basis of PTSD. However, only limited research has explored mobile EEG, which is important for scalability. This proof-of-concept study delves into mobile EEG-derived biomarkers for PTSD and their potential implications. Over four weeks, we measured PTSD symptoms using the PTSD checklist for DSM-5 (PCL-5) at multiple timepoints, and we recorded multiple EEG sessions from 21 individuals using a mobile EEG device. In total, we captured 38 EEG sessions, each comprising two recordings that lasted approximately 180 seconds, to evaluate reproducibility. Next, we extracted Shannon entropy, as a measure of the randomness or unpredictability of the signal and spectral power for the fronto-temporal regions of interest, including electrodes at AF3, AF4, T7, and T8 for each EEG recording session. We calculated the partial correlation between the EEG variables and PCL-5 measured closest to the EEG session, using age, sex, and the grouping variable 'batch' as covariates. We observed a significant negative correlation between Shannon entropy in fronto-temporal regions and PCL-5 scores. Specifically, this association was evident in the AF3 (r = -0.456, FDR-corrected p = 0.01), AF4 (r = -0.362, FDR-corrected p = 0.04), and T7 (r = -0.472, FDR-corrected p = 0.01) regions. Additionally, we found a significant negative association between the alpha power estimated from AF4 and PCL-5 (r=-0.429, FDR-corrected p=0.04). Our findings suggest that EEG data acquired using a mobile EEG device is associated with PTSD symptom severity, offering valuable insights into the neurobiological mechanisms underlying PTSD.
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The co-occurrence of substance use disorder (SUD) and posttraumatic stress disorder (PTSD) is common, and is associated with greater severity of symptoms, poorer treatment prognosis, and increased risk of return to substance use following treatment. Screening for PTSD is not routinely implemented in substance use treatment programs, despite clinical relevance. Identifying screening tools that minimize patient burden and allow for comprehensive treatment in this patient population is critical. The current study examined the utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) in identifying probable PTSD in a predominantly Black sample of 81 socioeconomically disadvantaged substance misusing hospital patients. The majority of the sample (75.3 %; n = 61) were found to meet criteria for probable PTSD using a suggested clinical cut score of 33 on the PTSD Checklist for DSM-5 (PCL-5). Diagnostic utility analyses were completed and determined a cut-score of 5 for the PC-PTSD-5 to demonstrate the best performance (SE = 0.62, κ(1) = 0.22; SP =.80, κ(0) = 0.61; EEF = 0.67, κ(0.5) = 0.32) in this sample. Results provide preliminary support for the use of the PC-PTSD-5 as a brief screening tool for probable PTSD in substance misusing patient populations. Routine use of the PC-PTSD-5 during assessment may be beneficial when treatment planning with those undergoing treatment for SUD because comprehensive assessment and treatment will provide a better chance of long-term recovery.
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Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Humanos , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Atención Primaria de Salud , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Trastornos Relacionados con Sustancias/diagnóstico , Poblaciones Vulnerables , Estatus Socioeconómico BajoRESUMEN
RATIONALE: Mycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. OBJECTIVES: The objectives of this study were to assess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection. METHODS: 7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the M. intracellulare infection were assessed using a series of linear mixed models. MEASUREMENTS AND MAIN RESULTS: Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14-21 days after inoculation. CONCLUSION: Endobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.
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Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Adulto , Animales , Femenino , Complejo Mycobacterium avium , Callithrix , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/microbiología , Callitrichinae , Citocinas , Mycobacterium aviumRESUMEN
Trauma-focused psychotherapy approaches are the first-line treatment option for post-traumatic stress disorder (PTSD); however, up to a third of patients remain symptomatic even after completion of the treatment. Predicting which patients will respond to a given treatment option would support personalized treatments and improve the efficiency of healthcare systems. Although previous neuroimaging studies have examined possible pre-treatment predictors of response to treatment, the findings have been somewhat inconsistent, and no other study has examined habituation to stimuli as a predictor. In this study, 16 treatment-seeking adults (MAge = 43.63, n = 10 women) with a primary diagnosis of PTSD passively viewed pictures of emotional facial expressions during functional magnetic resonance imaging (fMRI). After scanning, participants rated facial expressions on both valence and arousal. Participants then completed eight weekly sessions of prolonged exposure (PE) therapy. PTSD symptom severity was measured before and after treatment. Overall, participants showed symptomatic improvement with PE. Consistent with hypotheses, lesser activation in the amygdala and greater activation in the ventromedial prefrontal cortex during the presentation of fearful vs. happy facial expressions, as well as a greater decline in amygdala activation across blocks of fearful facial expressions at baseline, were associated with greater reduction of PTSD symptoms. Given that the repeated presentation of emotional material underlies PE, changes in brain responses with repeated stimulus presentations warrant further studies as potential predictors of response to exposure therapies.
RESUMEN
Streptococcus pneumoniae is a gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H(2)O(2)) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.