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1.
Stress ; 27(1)2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022295

RESUMO

Objective: People living with HIV (PLWH) experience high rates of childhood trauma exposure, which is a significant risk factor for the development of posttraumatic stress disorder (PTSD). Because Black Americans living in urban environments are exposed to high levels of trauma, suffer from chronic PTSD, and are at increased risk for HIV infection, it is important to understand how HIV status interacts with childhood maltreatment to influence PTSD symptom severity and underlying psychophysiology. Methods: The current cross-sectional study assessed whether HIV status interacts with childhood maltreatment to influence PTSD symptom severity and heart rate variability during a dark-enhanced startle (DES) task in 88 Black women with (n=30) and without HIV (n=58). Results: HIV was associated with greater PTSD symptom severity only in women with low levels of childhood maltreatment (p=.024). Startle potentiation during DES was highest in women living without HIV and with high childhood maltreatment (p=.018). In women who had experienced low levels of childhood maltreatment, respiratory sinus arrhythmia (RSA) was lower during the dark phase of DES in women living without HIV than women living with HIV (WLWH), (p=.046). RSA during the light phase of DES was lower in WLWH than in women living without HIV (p=.042). Conclusion: In the current sample of Black women, HIV status was associated with PTSD symptom severity in a manner dependent on level of childhood maltreatment, suggesting that HIV status may be an important factor to consider for behavioral and pharmacological treatment strategies for PTSD. Additionally, HIV status is associated with lower percent potentiation to darkness and lower RSA during the light phase of DES, suggesting physiological mechanisms by which HIV may contribute to PTSD symptoms in individuals exposed to low levels of childhood maltreatment.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Negro ou Afro-Americano , Infecções por HIV , Frequência Cardíaca , Reflexo de Sobressalto , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Frequência Cardíaca/fisiologia , Adulto , Estudos Transversais , Reflexo de Sobressalto/fisiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Psicofisiologia , Arritmia Sinusal Respiratória/fisiologia
2.
Nucleic Acids Res ; 50(19): 10964-10980, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36271797

RESUMO

Bacterial gene expression depends on the efficient functioning of global transcriptional networks, however their interconnectivity and orchestration rely mainly on the action of individual DNA binding proteins called transcription factors (TFs). TFs interact not only with their specific target sites, but also with secondary (off-target) sites, and vary in their promiscuity. It is not clear yet what mechanisms govern the interactions with secondary sites, and how such rewiring affects the overall regulatory network, but this could clearly constrain horizontal gene transfer. Here, we show the molecular mechanism of one such off-target interaction between two unrelated TFs in Escherichia coli: the C regulatory protein of a Type II restriction-modification system, and the RacR repressor of a defective prophage. We reveal that the C protein interferes with RacR repressor expression, resulting in derepression of the toxic YdaT protein. These results also provide novel insights into regulation of the racR-ydaST operon. We mapped the C regulator interaction to a specific off-target site, and also visualized C protein dynamics, revealing intriguing differences in single molecule dynamics in different genetic contexts. Our results demonstrate an apparent example of horizontal gene transfer leading to adventitious TF cross-talk with negative effects on the recipient's viability. More broadly, this study represents an experimentally-accessible model of a regulatory constraint on horizontal gene transfer.


Assuntos
Enzimas de Restrição-Modificação do DNA , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Enzimas de Restrição-Modificação do DNA/genética , Prófagos/genética , Prófagos/metabolismo , Regulação Bacteriana da Expressão Gênica , Escherichia coli/genética , Escherichia coli/metabolismo , Redes Reguladoras de Genes
3.
Depress Anxiety ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-39015247

RESUMO

Background: Posttraumatic stress disorder (PTSD) symptoms can develop following acute, life-threatening medical events. This study explores a potential biomarker of PTSD risk that is novel to a medical trauma population: a noninvasive, mobile skin conductance (SC) measurement. Methods: Participants (N=64) were enrolled in-hospital following a stroke or transient ischemic attack (TIA). Mobile measurement of SC reactivity to recalling the stroke/TIA traumatic event was conducted at hospital bedside in the days following the stroke/TIA. PTSD symptoms that developed in response to the stroke/TIA were measured at 1-month follow-up. We tested the association between SC reactivity and total 1-month PTSD symptoms, as well as PTSD symptom dimensions of fear and dysphoria. Results: In unadjusted analyses, there were significant positive associations between in-hospital SC reactivity to recalling the stroke/TIA traumatic event and higher-order fear-related symptoms (r=.30, p=.016), as well as lower-order fear-related symptoms of anxious arousal (r=.27, p=.035) and avoidance (r=.25, p=.043) at 1 month. Associations between SC reactivity and the fear, anxious arousal, and avoidance symptom dimensions remained significant in multivariable regression models that adjusted for relevant covariates including age, gender, stroke severity, medical comorbidity, and psychosocial factors. Although there was a positive association observed between SC reactivity to recalling the stroke/TIA event and total PTSD symptom severity at 1-month follow-up, it did not reach the level of statistical significance (r=.23, p=.070). Further, no significant association was detected for dysphoria-related symptoms (r=.11, p=.393). Conclusions: This is the first study to test the prospective association of SC reactivity with PTSD symptom development following a medical trauma. The findings indicate that mobile measures of SC reactivity may be useful for in-hospital identification of individuals at risk for fear-related PTSD symptom development following a medical event and highlight the potential mechanisms involved in the development of these symptoms following a medical event.

4.
Dev Psychopathol ; 35(3): 1159-1170, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-34689856

RESUMO

Early life adversity (ELA) has been linked with increased arousal responses to threat, including increased amygdala reactivity. Effects of ELA on brain function are well recognized, and emerging evidence suggests that caregivers may influence how environmental stressors impact children's brain function. We investigated the hypothesis that positive interaction between mother and child can buffer against ELA effects on children's neural responses to threat, and related symptoms. N = 53 mother-child pairs (children ages 8-14 years) were recruited from an urban population at high risk for violence exposure. Maternal caregiving was measured using the Parenting Questionnaire and in a cooperation challenge task. Children viewed fearful and neutral face stimuli during functional magnetic resonance imaging. Children who experienced greater violence at home showed amygdala sensitization, whereas children experiencing more school and community violence showed amygdala habituation. Sensitization was in turn linked with externalizing symptoms. However, maternal warmth was associated with a normalization of amygdala sensitization in children, and fewer externalizing behaviors prospectively up to 1 year later. Findings suggested that the effects of violence exposure on threat-related neural circuitry depend on trauma context (inside or outside the home) and that primary caregivers can increase resilience.


Assuntos
Exposição à Violência , Violência , Feminino , Humanos , Mães , Tonsila do Cerebelo/diagnóstico por imagem , Medo
5.
Nucleic Acids Res ; 49(19): e112, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34417617

RESUMO

Single-molecule (particle) tracking is a powerful method to study dynamic processes in cells at highest possible spatial and temporal resolution. We have developed SMTracker, a graphical user interface for automatic quantifying, visualizing and managing of data. Version 2.0 determines distributions of positional displacements in x- and y-direction using multi-state diffusion models, discriminates between Brownian, sub- or superdiffusive behaviour, and locates slow or fast diffusing populations in a standardized cell. Using SMTracker, we show that the Bacillus subtilis RNA degradosome consists of a highly dynamic complex of RNase Y and binding partners. We found similar changes in molecule dynamics for RNase Y, CshA, PNPase and enolase, but not for phosphofructokinase, RNase J1 and J2, to inhibition of transcription. However, the absence of PfkA or of RNase J2 affected molecule dynamics of RNase Y-mVenus, indicating that these two proteins are indeed part of the degradosome. Molecule counting suggests that RNase Y is present as a dimer in cells, at an average copy number of about 500, of which 46% are present in a slow-diffusive state and thus likely engaged within degradosomes. Thus, RNase Y, CshA, PNPase and enolase likely play central roles, and RNase J1, J2 and PfkA more peripheral roles, in degradosome architecture.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Endorribonucleases/metabolismo , Complexos Multienzimáticos/metabolismo , Polirribonucleotídeo Nucleotidiltransferase/metabolismo , RNA Helicases/metabolismo , RNA Bacteriano/genética , Imagem Individual de Molécula/métodos , Interface Usuário-Computador , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/ultraestrutura , Proteínas de Bactérias/genética , Difusão , Endorribonucleases/genética , Endorribonucleases/ultraestrutura , Exorribonucleases/genética , Exorribonucleases/metabolismo , Regulação Bacteriana da Expressão Gênica , Cinética , Simulação de Dinâmica Molecular , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/ultraestrutura , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Polirribonucleotídeo Nucleotidiltransferase/genética , Polirribonucleotídeo Nucleotidiltransferase/ultraestrutura , Ligação Proteica , Multimerização Proteica , RNA Helicases/genética , RNA Helicases/ultraestrutura , RNA Bacteriano/metabolismo , Ribonucleases/genética , Ribonucleases/metabolismo , Transcrição Gênica
6.
Nucleic Acids Res ; 49(7): 3826-3840, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744971

RESUMO

Restriction-modification (R-M) systems represent a first line of defense against invasive DNAs, such as bacteriophage DNAs, and are widespread among bacteria and archaea. By acquiring a Type II R-M system via horizontal gene transfer, the new hosts generally become more resistant to phage infection, through the action of a restriction endonuclease (REase), which cleaves DNA at or near specific sequences. A modification methyltransferase (MTase) serves to protect the host genome against its cognate REase activity. The production of R-M system components upon entering a new host cell must be finely tuned to confer protective methylation before the REase acts, to avoid host genome damage. Some type II R-M systems rely on a third component, the controller (C) protein, which is a transcription factor that regulates the production of REase and/or MTase. Previous studies have suggested C protein effects on the dynamics of expression of an R-M system during its establishment in a new host cell. Here, we directly examine these effects. By fluorescently labelling REase and MTase, we demonstrate that lack of a C protein reduces the delay of REase production, to the point of being simultaneous with, or even preceding, production of the MTase. Single molecule tracking suggests that a REase and a MTase employ different strategies for their target search within host cells, with the MTase spending much more time diffusing in proximity to the nucleoid than does the REase. This difference may partially ameliorate the toxic effects of premature REase expression.


Assuntos
Enzimas de Restrição-Modificação do DNA/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli , Escherichia coli/enzimologia , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Transferência Genética Horizontal
7.
J Trauma Stress ; 35(5): 1521-1534, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35776892

RESUMO

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.


Assuntos
Concussão Encefálica , Militares , Transtornos de Estresse Pós-Traumáticos , Encéfalo/diagnóstico por imagem , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/psicologia , Humanos , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/psicologia , Inconsciência/diagnóstico por imagem , Inconsciência/etiologia , Inconsciência/psicologia
8.
J Clin Psychol ; 78(6): 1220-1239, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34862625

RESUMO

OBJECTIVE: A large body of research has shown that alcohol use, drug use, aggression, and self-harm often co-occur within the same individuals, suggesting the possibility of shared etiologies. Research has yet to determine the factor structure of these dysregulated behaviors. METHODS: Participants (Mage = 40.33; 74% women) completed self-report and interview-based measures of dysregulated behaviors (alcohol use, drug use, aggression, and self-harm), emotion dysregulation, maladaptive personality traits, and symptoms of DSM disorders (e.g., borderline personality disorder [BPD], depression). RESULTS: Results showed support for a bifactor model (i.e., all indicators load on a common dysregulated behavior factor and on unique alcohol, drug, aggression, and self-harm factors), which provided a better fit to the data than other models. In line with our hypotheses, the general dysregulated behavior factor was positively associated with emotion regulation difficulties, negative affect, and BPD symptoms. CONCLUSIONS: These results have implications for several areas of psychopathology and intervention research.


Assuntos
Transtorno da Personalidade Borderline , Regulação Emocional , Comportamento Autodestrutivo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Agressão/psicologia , Transtorno da Personalidade Borderline/diagnóstico , Transtorno da Personalidade Borderline/epidemiologia , Feminino , Humanos , Masculino , Autorrelato
9.
Brain Behav Immun ; 91: 429-436, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152445

RESUMO

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.


Assuntos
Proteínas do Citoesqueleto/genética , Metilação de DNA , Cadeias beta de HLA-DP/genética , Transtornos de Estresse Pós-Traumáticos , Epigênese Genética , Epigenômica , Humanos , Transtornos de Estresse Pós-Traumáticos/genética
10.
Dev Sci ; 24(1): e13000, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497415

RESUMO

Risk for adverse outcomes, including the onset of mental illness, increases during adolescence. This increase may be linked to both new exposures, such as violence at home or in the community, or to physiological changes driven by puberty. There are significant sex differences in adolescent risk, for instance, anxiety disorders are significantly more prevalent in girls than boys. Fear learning is linked to mental health and may develop during adolescence, but the role of puberty in adolescent-specific change has not yet been systematically evaluated. We conducted a longitudinal study of fear learning that tested fear-potentiated startle (FPS) in 78 children (40 girls) aged 8-16 years. Participants completed two to three visits that included a differential fear conditioning task and self-report of both pubertal status and violence exposure. We tested for effects of sex, pubertal status, and violence exposure on FPS over time with latent growth curve models. We also examined the association between FPS and later anxiety symptoms. We found significant changes in FPS to the threat cue, but not the safety cue, across visits. Higher pubertal status was significantly associated with increased FPS to threat cues at each visit, whereas sex and violence exposure were not. FPS to threat during the baseline visit also predicted later anxiety symptoms. These findings suggest that puberty drives increased fear response to threat cues similarly for girls and boys, and that this effect may not be significantly impacted by individual differences in violence exposure during early adolescence.


Assuntos
Medo , Reflexo de Sobressalto , Adolescente , Ansiedade , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Puberdade
11.
Depress Anxiety ; 37(5): 429-437, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32248637

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is linked to a specific event, providing the opportunity to intervene in the immediate aftermath of trauma to prevent the development of this disorder. A previous trial demonstrated that trauma survivors who received three sessions of modified prolonged exposure therapy demonstrated decreased PTSD and depression prospectively compared to assessment only. The present study investigated the optimal dosing of this early intervention to test one versus three sessions of exposure therapy in the immediate aftermath of trauma. METHODS: Participants (n = 95) recruited from a Level 1 Trauma Center were randomly assigned in a 1.5:1.5:1 ratio in a parallel-group design to the three conditions: one-session exposure therapy, three-session exposure therapy, and assessment only. Follow-up assessments were conducted by study assessors blind to study condition. RESULTS: Mixed-effects model results found no significant differences in PTSD or depression symptoms between the control condition and those who received one or three exposure therapy sessions across 1-12-month follow-up assessment. Results indicate that the intervention did not interfere with natural recovery. Receiver operating characteristic curve analyses on the screening measure used for study inclusion (Predicting PTSD Questionnaire; PPQ) in the larger sample from which the treatment sample was drawn (n = 481) found that the PPQ was a poor predictor of likely PTSD at all follow-up time points (Area under the curve's = 0.55-0.62). CONCLUSIONS: This likely impacted study results as many participants demonstrated natural recovery. Recommendations for future early intervention research are reviewed, including strategies to identify more accurately those at risk for PTSD and oversampling more severe trauma types.


Assuntos
Terapia Implosiva/métodos , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes , Resultado do Tratamento
12.
Depress Anxiety ; 34(6): 502-507, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28221710

RESUMO

BACKGROUND: Increased psychophysiological reactivity is a hallmark intermediate phenotype of posttraumatic stress disorder (PTSD). Individuals with PTSD exhibit greater skin conductance (SC) responses to trauma scripts than trauma survivors without PTSD. However, trauma scripts require time for development and cannot be easily used in a single visit. Thus, there is a need for a low-cost, easy-to-use, SC recording protocol for PTSD assessment. METHODS: Using a mobile device (eSense) connected to a portable tablet computer, we assessed SC reactivity to a standard trauma interview (STI) in 63 participants recruited from Grady Memorial Hospital in Atlanta, GA, approximately 1 year after trauma exposure. SC response (SCR) was calculated by subtracting the SC level (SCL) at the end of the baseline recording from the maximum SCL during the STI. RESULTS: SCL was significantly higher during the STI compared to baseline (P < .001), and individuals with PTSD showed significantly greater SCR than individuals without PTSD (P = .006). Logistic regression using SCR with PTSD diagnosis as the outcome showed an odds ratio of 1.76 (95% CI: 1.11-2.78). Lastly, higher SCR during the STI was also significantly associated with PTSD symptom total score controlling for demographics and trauma severity (b = 0.42, P = .001). CONCLUSIONS: The current study demonstrated feasibility of the use of a mobile device for assessing psychophysiological reactivity in those with PTSD. The use of this low-cost, easy-to-use mobile device to collect objective physiological data in concert with a STI can be easily disseminated in clinical and research settings.


Assuntos
Resposta Galvânica da Pele/fisiologia , Entrevista Psicológica/métodos , Aplicativos Móveis , Monitorização Ambulatorial/métodos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Monitorização Ambulatorial/instrumentação
13.
Artigo em Inglês | MEDLINE | ID: mdl-38606374

RESUMO

Mindfulness-based cognitive therapy (MBCT) offers promise as a group-based intervention to alleviate posttraumatic stress disorder (PTSD) and depression symptoms in traumatized Black adults. Given the high level of barriers that exist for low-income Black adults, virtual delivery of MBCT may be helpful. This pilot randomized controlled trial assessed feasibility and acceptability of an adapted 8-week virtual MBCT group intervention for Black adults screening positive for PTSD and depression. Forty-six participants (89.3% women) recruited from an urban safety net hospital were randomized to MBCT or waitlist control (WLC). Overall feasibility was fair (70%); however, completion rates were higher for WLC than MBCT (90% vs. 54%). Group acceptability was high across quantitative and qualitative measures for study completers. Perceived barriers to psychological treatment were high (>9). While showing potential via improved coping skills and positive health changes, this intervention's success hinges on mitigating engagement barriers for future delivery; additional studies are warranted.

14.
Biol Sex Differ ; 15(1): 28, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549155

RESUMO

BACKGROUND: Traumatic events experienced in childhood can lead to increased risk of cardiovascular disorders in adulthood. Black Americans are disproportionately affected, as they are at increased risk for experiencing childhood trauma and cardiovascular diseases in adulthood. One of the hypothesized mechanisms of this association is through long-lasting dysregulation of the autonomic nervous system, a hallmark physiological biomarker of posttraumatic stress disorder (PTSD), which is twice as prevalent in women compared to men. METHODS: Ninety-one, majority Black American children, aged 9 were recruited to be a part of our longitudinal study of child development at research centers in Atlanta, GA and Detroit, MI. Resting HR was measured through a electrocardiogram (ECG) recording using the Biopac MP150. Self-report measures of violence exposure and PTSD symptoms were administered by research staff. RESULTS: Children with more violence exposure reported increased PTSS as well as lower resting HR. Regression analysis showed evidence of sex modifying this relationship, (B = -0.64, p < 0.05), such that the association between resting HR and PTSS was stronger in girls than in boys. In our exploratory analysis with standard clinical cutoffs of resting HR, the normative HR group was found to significantly moderate the relationship between violence exposure and PTSS in boys, (B = -2.14, p < 0.01), but not girls (B = -0.94, p = 0.27). CONCLUSION: In our sample of primarily Black urban children, we found that violence exposure was associated with slower, more adult-like HR, that girls showed greater PTSS associated with slower HR while boys did not, and that girls with lower than normative HR showed significantly higher PTSS compared to girls with normative HR. Our sample's demonstration of psychological consequences in addition to the physiological implications could provide new information about a psychobiological sequelae of violence exposure.


Experiencing traumatic events in childhood can lead to increased risk of heart disease in adulthood. One of the ways this might happen is through long-lasting changes of the autonomic nervous system. This system is dysregulated in posttraumatic stress disorder (PTSD), which is twice as common in women compared to men. We explored whether resting heart rate (HR), a measure of autonomic functioning was associated with violence exposure in children, and whether this relationship was different in boys and girls. We also explored whether categorizing our sample into resting HR groups based off standardized norms for HR predicted differing relationships between violence exposure and posttraumatic stress symptoms (PTSS). Because childhood trauma and heart disease impact Black Americans at greater rates, we recruited our sample of 92 nine-year-old children from research centers in Atlanta, GA and Detroit, MI. We measured their resting HR, exposure to violence, and PTSS. We found that violence exposure was associated with lower HR overall, that girls showed greater PTSS associated with lower HR when compared to boys, and that boys with lower than normative HR showed a stronger association between violence exposure and PTSS compared to boys with normative HR. Future studies should examine potential mechanisms underlying this sex difference to best understand the long-term cardiovascular consequences for sex-related health disparities. Specifically, longitudinal studies may be able to help researchers understand how reduced HR during adolescents might lead to future cardiovascular disease and psychopathology.


Assuntos
Exposição à Violência , Transtornos de Estresse Pós-Traumáticos , Criança , Adulto , Humanos , Masculino , Feminino , Estudos Longitudinais , Caracteres Sexuais , Frequência Cardíaca
15.
Front Psychiatry ; 15: 1140376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469033

RESUMO

Background: Mood disorders such as major depressive and bipolar disorders, along with posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and other psychotic disorders, constitute serious mental illnesses (SMI) and often lead to inpatient psychiatric care for adults. Risk factors associated with increased hospitalization rate in SMI (H-SMI) are largely unknown but likely involve a combination of genetic, environmental, and socio-behavioral factors. We performed a genome-wide association study in an African American cohort to identify possible genes associated with hospitalization due to SMI (H-SMI). Methods: Patients hospitalized for psychiatric disorders (H-SMI; n=690) were compared with demographically matched controls (n=4467). Quality control and imputation of genome-wide data were performed following the Psychiatric Genetic Consortium (PGC)-PTSD guidelines. Imputation of the Human Leukocyte Antigen (HLA) locus was performed using the HIBAG package. Results: Genome-wide association analysis revealed a genome-wide significant association at 6p22.1 locus in the ubiquitin D (UBD/FAT10) gene (rs362514, p=9.43x10-9) and around the HLA locus. Heritability of H-SMI (14.6%) was comparable to other psychiatric disorders (4% to 45%). We observed a nominally significant association with 2 HLA alleles: HLA-A*23:01 (OR=1.04, p=2.3x10-3) and HLA-C*06:02 (OR=1.04, p=1.5x10-3). Two other genes (VSP13D and TSPAN9), possibly associated with immune response, were found to be associated with H-SMI using gene-based analyses. Conclusion: We observed a strong association between H-SMI and a locus that has been consistently and strongly associated with SCZ in multiple studies (6p21.32-p22.1), possibly indicating an involvement of the immune system and the immune response in the development of severe transdiagnostic SMI.

16.
Psychol Trauma ; 15(5): 858-867, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36265048

RESUMO

OBJECTIVE: There is support for the use of mindfulness-based approaches with trauma-exposed adults. However, limited data are available on feasibility and acceptability of group-based mindfulness interventions in urban medical clinics serving primarily Black adults with low socioeconomic resources, where rates of trauma exposure are high. The present randomized pilot study evaluated the feasibility and acceptability of an 8-week adapted mindfulness-based cognitive therapy (MBCT) group for trauma-exposed Black adults who screened positive for posttraumatic stress disorder (PTSD) and depression in an urban primary care clinic setting. METHOD: Participants were randomized to waitlist control (WLC) or MBCT. Feasibility and acceptability were assessed through examination of retention rates, measures of group satisfaction and treatment barriers, and qualitative interview. Forty-two Black adults (85% women) were consented; of those, 34 (81%) completed preassessment and randomization. RESULTS: Feasibility of study design was shown, with > 75% (n = 26) of randomized participants completing the study through postassessment. Twenty-four individuals (70.5%) completed through 1-month follow-up. Results showed high levels of group acceptability across quantitative and qualitative measures. Perceived barriers to psychological treatment were high, with an average of > 6 barriers present. CONCLUSIONS: The findings indicate feasibility and acceptability of MBCT group interventions in urban primary care settings with trauma-exposed patients with significant psychopathology. However, substantial barriers to treatment engagement were endorsed and to improve numbers for successful engagement in the intervention, continued efforts to reduce treatment barriers and increase access to mindfulness-based interventions in underresourced communities are needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Atenção Plena , Transtornos de Estresse Pós-Traumáticos , Humanos , Adulto , Feminino , Masculino , Atenção Plena/métodos , Depressão/psicologia , Projetos Piloto , Estudos de Viabilidade , Atenção Primária à Saúde
17.
Chronic Stress (Thousand Oaks) ; 7: 24705470231156571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814781

RESUMO

Objective: Although several risk factors for stroke-induced posttraumatic stress disorder (PTSD) have been identified, objective risk measures that can be detected in the acute aftermath of these events are needed. This study is the first to collect an objective measure of psychophysiological arousal-skin conductance (SC) reactivity to a trauma interview-in patients after stroke or transient ischemic attack (TIA) and investigate correlates of SC reactivity. Methods: Mobile SC measurement during a resting baseline and standardized trauma interview was performed in-hospital in 98 individuals following stroke/TIA. We examined associations between several stroke-induced PTSD risk factors (sociodemographic, psychosocial, and medical characteristics) and SC reactivity to a trauma interview involving a free-response recalling of the stroke/TIA event. Results: Of the sociodemographic, psychosocial, medical characteristics examined as correlates to SC reactivity to recalling the stroke/TIA event, 2 factors reflecting aspects of prior and in-hospital experience were significantly associated with this indicator of sympathetic nervous system activation. A greater cumulative trauma burden was significantly associated with greater SC reactivity (r = .23, P = .04). Additionally, individuals administered benzodiazepines in-hospital had significantly greater SC reactivity to recalling the stroke/TIA event (M = 1.51, SD = 1.52) than those who were not (M = 0.76, SD = 1.16; P = .01). Greater cumulative trauma burden remained significantly associated with greater SC reactivity when adjusting for age and in-hospital benzodiazepine administration (ß=0.22, P = .04). Conclusion: This study demonstrated that SC reactivity was related to both behavioral and psychological risk factors for PTSD after a stroke/TIA event. Additionally, we demonstrated the feasibility of a low-cost, mobile measurement of SC that can be conducted in-hospital in a novel patient population: individuals with a medical trauma. With this measure, we were able to identify those individuals with the greatest trauma-related sympathetic nervous system reactivity in the days following a medical trauma. Future research is needed to determine whether SC reactivity may be leveraged in the development of brief, noninvasive screening measures for enhancing PTSD risk prediction.

18.
Cells ; 11(6)2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35326384

RESUMO

Bacteria are dependent on rapid alterations in gene expression. A prerequisite for rapid adaptations is efficient RNA turnover, with endonuclease RNase Y playing a crucial role in mRNA stability as well as in maturation. In Bacillus subtilis, RNase Y in turn interacts with the so-called "Y-complex" consisting of three proteins, which play important functions in sporulation, natural transformation and biofilm formation. It is thought that the Y-complex acts as an accessory factor in RNase Y regulation but might also have independent functions. Using single-molecule tracking, we show that all three Y-complex proteins exhibit three distinct mobilities, including movement through the cytosol and confined motion, predominantly at membrane-proximal sites but also within the cell center. A transcriptional arrest leads to a strong change in localization and dynamics of YmcA, YlbF and YaaT, supporting their involvement in global RNA degradation. However, Y-complex proteins show distinguishable protein dynamics, and the deletion of yaaT or ylbF shows a minor effect on the dynamics of YmcA. Cell fractionation reveals that YaaT displays a mixture of membrane association and presence in the cytosol, while YlbF and YmcA do not show direct membrane attachment. Taken together, our experiments reveal membrane-associated and membrane-independent activities of Y-complex proteins and a dynamic interplay between them with indirect membrane association of YmcA and YlbF via YaaT.


Assuntos
Bacillus subtilis , Proteínas de Bactérias , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Membrana Celular/metabolismo , Endorribonucleases/metabolismo , RNA/metabolismo , Ribonucleases/genética
19.
Psychol Trauma ; 14(7): 1089-1098, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31916804

RESUMO

OBJECTIVES: Parental posttraumatic stress disorder (PTSD) increases children's risk for emotional and behavioral problems. We examined parenting stress and parenting behavior quality as mediators of the relation between maternal PTSD and problematic child behaviors in a sample at high risk for trauma exposure. We also examined whether child sex moderated this association. METHOD: Participants were 141 African American mother-child dyads (children aged 8-12). Mothers reported PTSD severity, parenting stress, and child behavior (externalizing, internalizing, and emotional self-control). Parenting behavior quality (accounting for factors including parental warmth and engagement) was assessed from an observational parent-child interaction task. RESULTS: Parenting stress, but not observed parenting behavior quality, mediated the relation between maternal PTSD severity and child behaviors. Child sex moderated this association, such that the effect was stronger for girls. CONCLUSIONS: Maternal PTSD may be associated with negative child behavior outcomes, and this relation appears to be mediated by increased parenting stress. Stress-reducing interventions for parents with PTSD could improve child outcomes, especially for girls. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Comportamento Problema , Transtornos de Estresse Pós-Traumáticos , Criança , Comportamento Infantil/psicologia , Feminino , Humanos , Mães/psicologia , Poder Familiar/psicologia , Comportamento Problema/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia
20.
Neuropsychopharmacology ; 47(13): 2213-2220, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36114284

RESUMO

Female individuals are more likely to be diagnosed with PTSD following trauma exposure than males, potentially due, in part, to underlying neurobiological factors. Several brain regions underlying fear learning and expression have previously been associated with PTSD, with the hippocampus, amygdala, dorsal anterior cingulate cortex (dACC), and rostral ACC (rACC) showing altered volume and function in those with PTSD. However, few studies have examined how sex impacts the predictive value of subcortical volumes and cortical thickness in longitudinal PTSD studies. As part of an emergency department study completed at the Grady Trauma Project in Atlanta, GA, N = 93 (40 Female) participants were enrolled within 24 h following a traumatic event. Multi-echo T1-weighted MRI images were collected one-month post-trauma exposure. Bilateral amygdala and hippocampal volumes and rACC and dACC cortical thickness were segmented. To assess the longitudinal course of PTSD, the PTSD Symptom Scale (PSS) was collected 6 months post-trauma. We investigated whether regional volume/thickness interacted with sex to predict later PTSD symptom severity, controlling for PSS score at time of scan, age, race, and trauma type, as well as intracranial volume (ICV) for subcortical volumes. There was a significant interaction between sex and rACC for 6-month PSS, such that right rACC thickness was positively correlated with 6-month PSS scores in females, but not in males. In examining PTSD symptom subtypes and depression symptoms, greater rACC thickness in females predicted greater avoidance symptoms, while smaller rACC thickness in males predicted greater depression symptoms. Amygdala and hippocampus volume and dACC thickness showed no main effect or interaction with sex. The current findings provide evidence for sex-based differences in how brain volume predicts future PTSD severity and symptoms and supports the rACC as being a vital region regarding PTSD. Gender differences should be assessed in future longitudinal PTSD MRI studies for more accurate identification of future PTSD risk following trauma.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Estudos Prospectivos , Fatores Sexuais , Imageamento por Ressonância Magnética/métodos , Fatores de Risco
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