Interaction between PTSD-PRS and trauma affects PTSD likelihood in women victims of sexual assault.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is triggered by traumatic events, but genetic vulnerability and a history of childhood trauma are additional factors that may increase the risk of PTSD. Thus, our study focused on exploring the interaction between genetic susceptibility, as assessed by polygenic risk score (PRS), and traumatic events. METHODS: We evaluated 68 women with PTSD who had been sexually assaulted and 63 healthy controls without a history of sexual assault. DNA was genotyped using the Infinium Global Screening Array (Illumina), and PRS analysis was performed using PRSice. Furthermore, logistic regression models were employed to examine the interaction between childhood trauma, traumatic life events, and PTSD-PRS and how they contribute to the risk of developing PTSD. RESULTS: We found a significant association between PRS, childhood trauma (p = 0.03; OR = 1.241), and PTSD. Additionally, an interaction was observed between PRS, traumatic life events, and childhood trauma, particularly relating to physical and emotional neglect (p = 0.028; OR = 1.010). When examining neglect separately, we found a modest association between emotional neglect and PTSD (p = 0.014; OR = 1.086). CONCLUSIONS: Our findings highlight the importance of considering genetic vulnerability and traumatic experiences in understanding the etiology of PTSD.

Changes in attachment dimensions during the treatment of acute post-traumatic stress disorder in sexually assaulted Brazilian women.

Introduction: Attachment patterns are established during early childhood; however, extreme experiences throughout life may change this structure, either toward attachment security or insecurity. We analyzed changes in attachment dimensions in women with acute post-traumatic stress disorder (PTSD) following sexual assault, that were randomized to a 14-week treatment with either the medication sertraline or Interpersonal Psychotherapy. Methods: Seventy-four adult women who presented significant reduction in PTSD symptoms across the trial responded to the Revised Adult Attachment Scale at baseline, on week 8 of treatment, and at the end of the trial, on week 14. We fitted a generalized linear model to explain the attachment anxiety and avoidance scores at baseline. A generalized linear mixed model investigated how attachment dimensions changed over time. Socioeconomic data, treatment type, history of childhood trauma, and PTSD severity over the 14-week period were the considered covariates. Results: At baseline, attachment anxiety was associated with a history of early trauma. Attachment anxiety remained stable during the follow-up. Attachment avoidance, on the other hand, significantly increased from baseline to week 14. Higher avoidance was observed in patients with higher total PTSD scores and on the cluster of hyperarousal symptoms. Races other than White (black, mixed-race, or Asian) and younger age were associated with higher attachment avoidance. Discussion: Contrary to our expectations, attachment avoidance increased during follow-up, indicating changes in the interpersonal realm beyond the symptoms of PTSD.

Brazilian Psychiatric Association guidelines for the treatment of generalized anxiety disorder (GAD). Pharmacological and Psychotherapy approach. Perspectives.

OBJECTIVE: To combine elements of a systematic review and critical review to produce best evidence synthesis for the treatament of GAD. METHOD: There was included systematic reviews, metanalysis, and randomized controlled trials. Descriptor used was "generalized anxiety disorder", resulting in 4860 articles and 7 other studies, of which 59 were selected. RESULTS: Antidepressants and benzodiazepines are indicated, as well as pregabalin. From, atypical antipsychotics quetiapine has been studied. Cognitive behavior therapy (third wave of behavioral and cognitive therapies) as well as individual CBT proven to be effective. CONCLUSION: There is extensive literature on many effective treatments for GAD. The present work summarizes the therapeutic possibilities, emphasizing those available in the Brazil. Further studies are still needed to compare other available medications, to assess psychotherapies in more depth, new treatments and specially to assess the ideal time for maintaining therapy.

Antibody responses to Influenza vaccination are diminished in patients with inflammatory bowel disease on infliximab or tofacitinib.

BACKGROUND AND AIMS: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with IBD. METHODS: We conducted a prospective study including 213 IBD patients and 53 healthy controls; 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination and interval between vaccination and sampling. RESULTS: Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (Geometric Mean Ratio 0.35 [95% CI 0.20-0.60], p=0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p=0.0050) and tofacitinib (0.28 [0.14-0.57], p=0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p=0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p=0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p=0.017) and tofacitinib (0.23 [0.10-0.56], p=0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 (r=0.27; p=0.0004) and H1N1 (r=0.33; p<0.0001). CONCLUSIONS: Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to Influenza/A, similar to COVID-19 vaccine-induced antibody responses.

Neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 and wild-type virus in patients with inflammatory bowel disease following three doses of COVID-19 vaccine (VIP): a prospective, multicentre, cohort study.

Background: Patients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant. Methods: In this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664). Findings: Both heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in patients with IBD on infliximab (Geometric Mean Ratio (GMR) 0.19 [0.10, 0.36], p < 0.0001), infliximab and thiopurine combination (GMR 0.25 [0.13, 0.49], p < 0.0001) or tofacitinib (GMR 0.43 [0.20, 0.91], p = 0.028), but not in patients on thiopurine monotherapy, ustekinumab, or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against wild-type (p = 0.037) and BA.4/5 (p = 0.045). Interpretation: A third dose of a COVID-19 mRNA vaccine based on the wild-type spike glycoprotein significantly boosts neutralising antibody titres in patients with IBD. However, responses are lower against the Omicron variant BA.4/5, particularly in patients taking anti-TNF and JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed patients with IBD may receive additional benefit from bivalent vaccine boosters which target Omicron variants. Funding: Pfizer.

The relationship between tonic immobility and the development, severity, and course of posttraumatic stress disorder: Systematic and meta-analytic literature review.

BACKGROUND: Tonic immobility (TI) is a reflexive, involuntary response that causes motor inhibition, vocal suppression, and analgesia. TI is elicited by extreme fear and perception of entrapment in a life-threatening situation. Research suggests that TI is a frequent peritraumatic response and may be related to subsequent posttraumatic stress disorder (PTSD). However, findings are mixed and, as of yet, no systematic or meta-analytic review examining associations between TI and PTSD has been published. OBJECTIVE: We systematically and meta-analytically reviewed the literature and investigated whether TI is associated with the development, severity, and course of PTSD. Additionally, we evaluated whether different types of traumatic events are differentially associated with TI, and whether TI severity differs according to sex. METHODS: A systematic literature search was conducted using Embase, PubMed, PsycINFO, and Scopus. Meta-analyses were performed on the included articles. RESULTS: We identified 27 eligible articles. We found a significant association between TI and PTSD symptom severity (r = 0.39, 95% CI: 0.34-0.44; p < .0001). TI was more severe among females (Cohen's d=0.37, 95% CI: 0.25-0.48; p < .0001) and was more often elicited in situations involving interpersonal violence. We found limited longitudinal data to perform a meta-analysis of the association between TI and the development and/or course of PTSD. However, the literature available seems to support the role of TI in both the development and course of PTSD. CONCLUSIONS: Peritraumatic TI is associated with PTSD symptom severity, occurs more often during interpersonal violence, and is more severe among females. More longitudinal research is needed to investigate the role of TI in psychopathology development and course.

Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims.

Introduction: Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long interspersed nuclear elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA. Methods: This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1 = 19, NW2 = 10; PTSDCSA-: NW1 = 45, NW2 = 21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5'UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpG sites methylation and PTSD symptoms. Results: We found a negative association between CpG2 methylation and hyperarousal symptoms among those in the PTSDCSA+ group in W1 (adjusted p = 0.003) compared to the PTSDCSA- group (p > 0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal analysis, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA. Conclusion: Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.

Sleep characteristics and inflammatory markers in women with post-traumatic stress disorder.

INTRODUCTION: Sexual violence is one of the most severe traumatic events. It is associated with a higher risk for post-traumatic stress disorder (PTSD) development. Sleep disturbances such as insomnia are frequently reported by PTSD patients and play a key role in the development and course of the disorder. Sleep disturbances are associated with higher levels of pro-inflammatory cytokines emphasizing the importance of sleep studies in individuals with PTSD. OBJECTIVES: To investigate the association between subjective and objective sleep measurements and PTSD symptoms with inflammatory markers in women with PTSD following sexual assault. METHODS: In this longitudinal study fifty-seven women with PTSD were evaluated for sleep measurements and inflammatory markers. Participants completed the Clinician-Administered PTSD Scale, the Beck Depression Inventory, the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index. In addition, patients underwent full in-lab polysomnography and serum levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) measurement. All assessments were performed at baseline and after one year. Patients received pharmacological and/or psychological interventions between baseline and one-year follow-up. RESULTS: Despite improving PTSD symptoms severity and sleep quality (expressed in PSQI), we found an increase in the inflammatory markers IL-1ß, TNF-α, IL-6 and CRP after one year of follow-up. These findings suggest that neurobiological processes may advance independently of PTSD symptoms. We found a significant increase in the levels of IL-1ß and TNF-α associated with decreased slow-wave sleep (p = 0.019 and p = 0.018 respectively), IL-6 associated with arousal index (p = 0.024), and CRP associated with insomnia severity (p = 0.012), and sleep duration longer than 6 h per night (p < 0.001). CONCLUSIONS: Sleep impairments in PTSD may be associated with a gradual and persistent alteration in the immune system, resulting in a progressive inflammatory process. Our results suggest that sleep mechanisms are involved in this incident inflammatory process in young women with PTSD.

The Relationship between Lifetime Exposure to Potentially Traumatic Events, Peritraumatic Dissociation, and PTSD in a Sample of Sexually Assaulted Women in Sao Paulo, Brazil.

Sexually assaulted women represent a particularly high-risk group for developing post-traumatic stress disorder (PTSD). Potentially traumatic events (PTEs) and peritraumatic dissociation (PD) are known risk factors for PTSD. However, little is known about how previous trauma affects PD and how this relationship affects PTSD. We aimed to investigate whether PD acts as a mediator between PTEs and PTSD severity in a sample of recently sexually assaulted women in Sao Paulo, Brazil. Seventy-four sexually assaulted women aged 18-44 completed questionnaires and structured interviews on PTSD, PD, and PTEs. We examined direct and indirect effects of variables using causal mediation analysis. Lifetime exposure to PTEs was a risk factor for PD, but PD was not a risk factor for PTSD symptom severity. Also, PD was not a mediator between PTEs and PTSD severity. We provided recommendations on how to further explore the relationship between lifetime traumatic exposure, PTSD, and peritraumatic dissociation.

Peri-Traumatic Dissociation and Tonic Immobility as Severity Predictors of Posttraumatic Stress Disorder After Rape.

Some individuals show abnormal reactions to extreme fear and life-threatening situations, including tonic immobility (TI) and peri-traumatic dissociation (PTD). We aimed to investigate the association of TI and PTD with posttraumatic stress disorder (PTSD) in women who experienced sexual violence and the risk factors for PTD occurrence. We compared PTSD severity in 86 young adult women with PTSD after a sexual violence exposure grouped according to the presence of PTD and TI. In addition, we investigated whether PTD is associated with depression and anxiety symptoms and assessed potential risk factors for PTD reaction. We found a significant positive correlation between PTSD severity and PTD occurrence (R2 = .132; p = .001). PTD was also positively correlated with all clusters of PTSD symptoms except the Clinician-Administered PTSD Scale avoidance cluster (p = .058). PTD was strongly correlated with anxiety (R2 = .619; p < .001) and depressive symptoms (R2 = .547; p < .001). Multiple logistic regression showed that history of physical abuse (odds ratio [OR]: 1.386; p = .011) and sexual abuse (OR: 1.947; p = .004) during childhood were associated with PTD occurrence. Other risk factors for PTD were having less years of study (OR: 0.216; p = .016) and lower income (OR: 7.403; p = .028). TI measures were available for a subsample of 29 women. We found no association between TI and PTSD severity. PTD, but not TI, is significantly associated with more severe PTSD, depressive, and anxiety symptoms. Less-educated women with a history of childhood abuse and a lower income are at risk of PTD occurrence during a sexual violence episode.

Moral injury and mental health among health-care workers during the COVID-19 pandemic: meta-analysis.

Background: During the COVID-19 pandemic, health-care workers (HCWs) may have been confronted with situations that may culminate in moral injury (MI). MI is the psychological distress that may result from perpetrating or witnessing actions that violate one's moral codes. Literature suggests that MI can be associated with mental health problems.Objective: We aimed to meta-analytically review the literature to investigate whether MI is associated with symptoms of posttraumatic stress disorder (PTSD), anxiety, depression, burnout, and suicidal ideation among active HCWs during the COVID-19 pandemic.Method: We searched eight databases for studies conducted after the onset of the COVID-19 pandemic up to 18 July 2023, and performed random-effects meta-analyses to examine the relationship between MI and various mental health outcomes.Results: We retrieved 33 studies from 13 countries, representing 31,849 individuals, and pooled 79 effect sizes. We found a positive association between MI and all investigated mental health problems (rs = .30-.41, all ps < .0001). Between-studies heterogeneity was significant. A higher percentage of nurses in the samples was associated with a stronger relationship between MI and depressive and anxiety symptoms. Samples with a higher percentage of HCWs providing direct care to patients with COVID-19 exhibited a smaller effect between MI and depressive and anxiety symptoms. We observed a stronger effect between MI and PTSD symptoms in US samples compared to non-US samples.Conclusion: We found that higher MI is moderately associated with symptoms of PTSD, anxiety, depression, burnout, and suicidal ideation among HCWs during the COVID-19 pandemic. Our findings carry limitations due to the array of MI scales employed, several of which were not specifically designed for HCWs, but underscore the need to mitigate the effect of potentially morally injurious events on the mental health of HCWs.

We conducted the first meta-analysis of moral injury and mental health among healthcare workers.Moral injury is moderately associated with symptoms of PTSD, depression, anxiety, burnout, and suicidal ideation.There was a stronger association between MI and anxiety and depressive symptoms for samples with more nurses.

The positive impact of an intervention for maternal depression on child emotional and behavioral symptoms in a low-resource setting

Objectives: Children of depressed mothers are at risk of developing mental health problems. We sought to determine whether treatment for maternal depression by community-based health workers would decrease behavioral/emotional symptoms in their children. Interventions for maternal depressive symptoms in a low/middle-income country can have a high global impact. Methods: Community-based health workers were trained to deliver a psychosocial intervention for mothers with depression in a primary care setting. A total of 49 mothers and 60 children were assessed pre-intervention, post-intervention, and at 6 months follow-up. Child behavioral/emotional symptoms were evaluated according to type of change in maternal depressive symptoms: response or remission. Results: An overall decrease in maternal depressive symptoms from baseline to post-intervention and 6 months follow-up were found. Response or remission was associated with better outcomes in child behavioral/emotional symptoms at 6 months follow-up (p = 0.0247, Cohen's d: 0.76; p = 0.0224, Cohen's f: 0.44) but not at post-intervention (p = 0.1636, Cohen's d: 0.48; p = 0.0720, Cohen's f: 0.33). Conclusions: Improvement in maternal depression was related to decreased behavioral/emotional symptoms in their children. Our results suggest that providing interventions for maternal depression in primary care is a viable strategy to prevent behavioral/emotional symptoms in the next generation. Clinical Trial registration: Brazilian Clinical Trials, number RBR-5qhmb5.

Meta-analysis of the effect of racial discrimination on suicidality.

Racial discrimination (RD) is unfair treatment of individuals based on race or ethnicity. It is a pervasive and increasing phenomenon in the lives of many individuals with deleterious effects on mental health. Research implicates RD in diminished well-being, lower life satisfaction and self-esteem, and mental health disorders. Furthermore, there have been reports that minorities and marginalized groups exposed to RD are at a higher risk of suicide. Given that RD negatively impacts mental health and that suicide is a major public health concern, we meta-analytically reviewed the literature to investigate whether RD is associated with suicidal ideation (SI) and suicide attempt (SA). We identified 43 eligible articles investigating the association between RD and suicidality through PubMed, Embase, PsycINFO and Scopus, from which we pooled 39 effect sizes for SI (58,629 individuals) and 15 for SA (30,088 individuals). Results demonstrated that RD has a small but significant effect both on SI (r = 0.16, 95% CI: 0.12 to 0.19; p < 0.0001) and on SA (r = 0.13, 95% CI: 0.02 to 0.23; p = 0.018). We found no indication of publication bias, and fail-safe tests confirmed the robustness of the results. Furthermore, we tested the moderating effects of several study characteristics (e.g., age, race, RD and SI time frame assessment, and categorization of RD measures). The only study characteristic to moderate the effect of RD on SI was SI time frame assessment (r = 0.07; 95% CI: 0.015 to 0.12; p = 0.01). Our findings suggest that SI and SA are phenomena that may be influenced by exposure to RD. Thus, individuals that are discriminated based on race may develop more suicidal thoughts and an increased likelihood of attempting suicide. These findings underscore the need for more prevention and intervention efforts to attenuate the effect of RD on suicidality.

Interpersonal psychotherapy versus sertraline for women with posttraumatic stress disorder following recent sexual assault: a randomized clinical trial.

Background: Sexual assault often triggers posttraumatic stress disorder (PTSD), a potentially chronic severe mental disorder. Most guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and trauma-focused psychotherapies as treatment options. Interpersonal Psychotherapy (IPT), adapted for PTSD (IPT-PTSD), focuses on interpersonal consequences of trauma rather than confronting the trauma itself. Studies have found IPT-PTSD efficaciously reduced PTSD symptoms with limited attrition. No efficacy trials have compared IPT-PTSD and SSRI. We hypothesized IPT would reduce PTSD, anxiety, and depressive symptoms more than sertraline among women with PTSD following a recent sexual assault. Objectives: To compare the efficacy of IPT-PTSD to SSRI sertraline in a 14-week randomized clinical trial for women with PTSD following a recent sexual assault. Methods: Seventy-four women with PTSD who had suffered sexual assault in the last six months were randomly assigned to 14 weeks of IPT-PTSD (n = 39) or sertraline (n = 35). Instruments assessed PTSD, anxiety, and depressive symptoms. This randomized clinical trial was conducted in São Paulo, Brazil, using the Clinician-Administered PTSD Scale-5 (CAPS-5) as the primary outcome measure. Results: Both treatments significantly reduced PTSD, anxiety, and depressive symptoms, without between-group outcome differences. CAPS-5 mean decreased from 42.5 (SD = 9.4) to 27.1 (SD = 15.9) with sertraline and from 42.6 (SD = 9.1) to 29.1 (SD = 15.5) with IPT-PTSD. Attrition was high in both arms (p = .40). Conclusions: This trial showed within-group improvements without differences between IPT-PTSD and sertraline treatment of PTSD. Our findings suggest that non-exposure-based psychotherapies may benefit patients with PTSD, although we did not directly compare these treatments to an exposure therapy. Brazilian Clinical Trials Registry RBR-3z474z.

Antecedentes: La agresión sexual con frecuencia gatilla un trastorno de estrés postraumático (TEPT), un trastorno mental severo potencialmente crónico. La mayoría de las guías clínicas recomiendan los inhibidores selectivos de la receptación de serotonina (ISRSs) y psicoterapias focalizadas en trauma como opciones de tratamiento. La Psicoterapia Interpersonal (PIP), adaptada para TEPT (PIP-TEPT), se focaliza en las consecuencias interpersonales del trauma en lugar de confrontar el trauma en sí. Los estudios han encontrado que la PIP-TEPT eficazmente redujo los síntomas de TEPT con una deserción limitada. Ningún ensayo de eficacia ha comparado PIP-TEPT e ISRS. Hipotetizamos que la PIP-TEPT puede reducir los síntomas de TEPT, ansiedad y depresión más que la sertralina entre las mujeres con TEPT después de una agresión sexual reciente.Objetivos: Comparar la eficacia de la PIP-TEPT con sertralina, un ISRS en un ensayo clínico aleatorizado de 14 semanas para mujeres con TEPT después de una agresión sexual reciente.Métodos: Setenta y cuatro mujeres con TEPT que habían sufrido de una agresión sexual en los últimos seis meses fueron asignadas aleatoriamente a 14 semanas de PIP-TEPT (n = 39) o sertralina (n = 35). Los instrumentos evaluaron síntomas de TEPT, ansiedad y depresión. Este ensayo clínico aleatorizado se realizó en San Pablo, Brasil, utilizando la Escala de TEPT administrada por el clínico (CAPS-5, por sus siglas en inglés) como medida de resultado primaria.Resultados: Ambos tratamientos redujeron significativamente los síntomas de TEPT, ansiedad y depresión, sin diferencias de resultados entre los grupos. La media del CAPS-5 se redujo de 42.5 (DE = 9.4) a 27.1 (DE = 15.9) con sertralina y de 42.6 (DE = 9.1) a 29.1 (DE = 15.5) con la PIP-TEPT. La deserción fue alta en ambos tratamientos (p = .40).Conclusiones: Este ensayo mostro mejoría entre grupos sin diferencias entre la PIP-TEPT y sertralina en el tratamiento del TEPT. Nuestros hallazgos sugieren que las psicoterapias no basadas en la exposición pueden beneficiar a los pacientes con TEPT, aunque no comparamos directamente estos tratamientos con una terapia de exposición.Registro Brasileño de Ensayos Clínicos RBR-3z474z.

Increased immuno-inflammatory mediators in women with post-traumatic stress disorder after sexual assault: 1-Year follow-up.

BACKGROUND: Sexual violence is a traumatic event that can trigger post-traumatic stress disorder (PTSD) and generate biological responses to stress characterized by inhibiting the hypothalamic-pituitary axis (HPA), altering immune activity, and changing the structure and function of the brain. PTSD is associated with increased levels of inflammatory markers. This study aimed to measure differences in inflammatory markers and HPA hormone levels between women with PTSD due to sexual violence and controls at baseline and after 1-year follow-up. METHODS: Fifty-eight women with PTSD resulting from sexual assault occurring up to 6 months prior were compared to 41 female controls. The patients were followed for 1 year. At baseline (T1), we measured inflammatory biomarkers. We also applied the Mini International Neuropsychiatric Interview (MINI), the Clinician-Administered Post-Traumatic Stress Disorder Scale-5, the Beck Depression Inventory, the Beck Anxiety Inventory, and the Childhood Trauma Questionnaire. The patients were randomized to receive treatment with sertraline or interpersonal psychotherapy for 14 weeks (T2) and then continued the usual treatment if deemed necessary for 1 year. The same interviews and examinations were repeated after 1 year (T3). RESULTS: At baseline, the patients had significantly higher adrenocorticotropic hormone levels, compared to controls; however, there was no baseline difference in inflammatory markers or cortisol. After 1 year, there were significantly higher levels of interleukin-1ß (p < 0.0001), monocyte chemoattractant protein-1 (p < 0.0001), tumor necrosis factor-α (p < 0.0001), c-reactive protein (p < 0.0001), and cortisol (p = 0.046) in the patient group. In addition to PTSD, 56 patients presented with a major depressive episode at T1 (according to the MINI). At the end of 1 year, there was a significant improvement in depressive (p < 0.001), anxiety (p = 0.03), and PTSD symptoms (p < 0.001) regardless of the treatment received. DISCUSSION: The increase of the inflammatory markers after 1 year, even with symptomatic improvement, may indicate that PTSD following sexual violence is associated with high depressive symptoms. This association may have a different pattern of immunoendocrine alterations than PTSD only. Furthermore, these alterations may persist in the long term, even with the improvement of the symptoms, probably generating an immunological imprint that can lead to future clinical consequences. This study adds to the current knowledge of PTSD neurobiology and contributes to broadening approaches to this disorder.

COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study.

BACKGROUND: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose. METHODS: VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28-49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data. FINDINGS: Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11-0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31-0·87]; p=0·012), and thiopurine (0·69 [0·51-0·95]; p=0·021), but not with ustekinumab (0·64 [0·39-1·06]; p=0·083), or vedolizumab (0·84 [0·54-1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22-2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80-0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021). INTERPRETATION: A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors. FUNDING: Pfizer.

The positive impact of maternal depression intervention on children's emotional and behavioral symptoms in a low-resource setting.

OBJECTIVE: Children of depressed mothers are at risk of developing mental health problems. We sought to determine whether treatment for maternal depression delivered by community health workers (CHW) would decrease behavioral/emotional symptoms in their child. An intervention treating maternal depressive symptoms in a low-middle-income country can have a high global impact. METHODS: CHW were trained to deliver a psychosocial intervention for mothers with depression in a primary care setting. 49 mothers and 60 children were assessed pre-intervention, post-intervention, and at a 6-months follow-up. Child behavioral/emotional symptoms were evaluated by type of change in maternal depressive symptoms: remission and response. RESULTS: An overall decrease in maternal depressive symptoms from baseline to post-intervention and 6-month follow-up were found. Remission and response of maternal depression was associated with better outcomes related to child´s behavioral/emotional symptoms at the 6-month follow-up (p = 0.0247, Cohen's d: 0.76; p = 0.0224, Cohen's f: 0.44) but not at post-intervention (p = 0.1636, Cohen's d: 0.48; p = 0.0720, Cohen's f: 0.33). CONCLUSION: Maternal depression improvement was related to their child's decreased behavioral/emotional symptoms. Our results suggest that interventions addressing maternal depression in primary care is a viable strategy to prevent behavioral/emotional symptoms in the next generation.

Shorter Telomeres Related to Posttraumatic Stress Disorder Re-experiencing Symptoms in Sexually Assaulted Civilian Women.

Telomeres are short tandem repeats of "TTAGGG" that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls - HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = -0.16; confidence interval (CI) 95% = -0.027--0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.