Can you remember silence? Epigenetic memory and reversibility as a site of intervention.

Just over 20 years ago, molecular biologists Leonie Ringrose and Renato Paro published an article with a provocative title, "Remembering Silence", in BioEssays. The article focused on how epigenetic elements could return to their silent state, operationally defined as their epigenetic status before their modulation by experimental or environmental factors. Though Ringrose and Paro's article was on fruit flies and factors affecting embryological growth, the article asked a question of considerable importance to rapidly expanding research in neuroepigenetics on the correlation between trauma and neuropsychiatric risk: If you experience a traumatic event and, as a result, acquire an epigenetic trait that is considered pathological, can you free yourself of that trait? Ultimately, we are interested in how a return to silence is envisioned in neuroepigenetics research, how interventions purported to bring about that silence might function, and what this might mean for people who live in the aftermath of trauma.

Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Prevalence of anxiety, depression, and post-traumatic stress disorder among Omani children and adolescents diagnosed with cancer: a prospective cross-sectional study.

BACKGROUND: Children and adolescents diagnosed with cancer often experience psychological distress, encompassing anxiety, depression, and post-traumatic stress disorder (PTSD). This study aimed to evaluate the prevalence of these conditions among Omani children and adolescents diagnosed with cancer, alongside identifying contributing factors. METHODS: A prospective cross-sectional study was conducted from October 2021 to June 2023 among a cohort of Omani children and adolescents (6-18 years old) diagnosed with cancer at three primary cancer referral centres in Oman. Validated Arabic-language versions of the Screen for Child Anxiety Related Disorders, the Center for Epidemiologic Studies Depression Scale for Children, and the Impact of Event Scale-Revised instruments were used to assess symptoms of anxiety, depression, and PTSD, respectively. An initial assessment (T1) was undertaken within the first 3 months of diagnosis, followed by a second assessment (T2) 3-6 months later. RESULTS: Of 113 eligible participants, 101 agreed to participate in the study (response rate: 95.6%), with 92 (91.0%) completing both assessments and included in the final analysis. Prevalence rates of anxiety, depression, and PTSD decreased from 43.5%, 56.5%, and 32.6%, respectively, at T1, to 38.0%, 35.9%, and 23.9% at T2. All average scores were below diagnostic cut-off points, except for the depression score at T1. Anxiety and depression scores decreased significantly (p = 0.043 and 0.001, respectively) between T1 and T2, as did the overall prevalence of depression (p = 0.004). At T1, linear regression analysis showed significant correlations between anxiety scores and the child's age and PTSD score (p < 0.05); these variables were also correlated with depression scores (p ≤ 0.001). At T2, significant correlations were observed between anxiety scores and the child's age and PTSD scores (p < 0.001). At both T1 and T2, anxiety, depression, and PTSD scores remained significantly correlated (p < 0.001). CONCLUSIONS: Omani children and adolescents recently diagnosed with cancer exhibit a high prevalence of anxiety, depression, and PTSD over time. Age-appropriate communication, ongoing support, and mental health services are recommended to help this patient group cope with their diagnosis and manage their emotional wellbeing. There is a need for future research to determine the effectiveness of specific psychological interventions in reducing the frequency of these disorders.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

BACKGROUND: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. METHODS: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. RESULTS: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. CONCLUSIONS: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Neighborhood social composition and refugee mental health - quasi-experimental evidence of associations from a Danish population register study.

BACKGROUND: Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design. METHODS: We followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders. RESULTS: Refugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06-1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05-1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03-1.50). We found no statistically significant associations with proportion of migrants. CONCLUSIONS: For refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.

A longitudinal investigation of caregiving and adolescent post-traumatic stress symptoms during COVID-19: evidence for high resting RSA as a susceptibility factor.

BACKGROUND: Post-traumatic stress symptoms (PTSS) were the most frequently reported mental health concern for youth during COVID-19, yet variations in youth's PTSS responses warrant empirical consideration. Features of the caregiving environment influence youth's responses to environmental stressors, and youth's parasympathetic nervous system regulation may qualify the magnitude and/or direction of these effects. This prospective investigation evaluated diathesis stress and differential susceptibility models of caregiving and parasympathetic influences on youth's PTSS responses to COVID-19. METHOD: Participants were 225 caregiver-youth dyads (youth 49.8% female at birth; 88.4% non-white) followed from childhood through adolescence and COVID-19. Youth's resting respiratory sinus arrhythmia (RSA; Mage = 6.11, s.d. = 0.21), caregiving features (i.e. attachment security [youth Mage = 12.24, s.d. = 0.35] and caregiver internalizing psychopathology [caregiver Mage = 39.29, s.d. = 6.78]) were assessed pre-pandemic. Youth's PTSS was assessed one year prior to the US COVID-19 pandemic (Mage = 14.24, s.d. = 0.50) and during the spring of 2020 at the height of the pandemic (Mage = 15.23, s.d. = 0.57). RESULTS: Youth's PTSS increased during COVID-19. Youth with relatively high resting RSA evidenced the lowest PTSS when their caregiving environment featured high attachment security or low caregiver internalizing problems, but the highest PTSS when their caregiving environment featured low attachment security or high caregiver internalizing problems. In contrast, PTSS levels of youth with relatively low or average resting RSA did not differ significantly depending on attachment security or caregiver internalizing. CONCLUSIONS: Results are consistent with a differential susceptibility hypothesis, wherein relatively high resting RSA conferred heightened sensitivity to caregiving environments in a for-better-and-for-worse manner during COVID-19.

Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Salivary inflammatory biomarkers as a predictor of post-traumatic stress disorder and depressive symptom severity in trauma patients: A prospective study.

BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression screening are recommended for traumatic injury patients, routine screening is still uncommon. Salivary inflammatory biomarkers have biological plausibility and potential feasibility and acceptability for screening. This study tested prospective associations between several salivary inflammatory biomarkers (proinflammatory cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α; and C-reactive protein), collected during hospitalization and PTSD and depressive symptoms at 5-month follow-up. METHODS: Adult traumatic injury patients (N = 696) at a major urban Level 1 trauma center provided salivary samples and completed PTSD and depressive symptom measures during days 0-13 of inpatient hospitalization. At 5-month follow-up, 368 patients (77 % male, 23 % female) completed the Clinician-Administered PTSD Scale for DSM-IV and the Self-rated Inventory of Depressive Symptomatology. Analyses focused on a latent inflammatory cytokine factor and C-reactive protein at baseline predicting 5-month PTSD and depression symptom outcomes and included baseline symptom levels as covariates. RESULTS: A latent factor representing proinflammatory cytokines was not related to 5-month PTSD or depressive symptom severity. Higher salivary CRP was related to greater PTSD symptom severity (ß = .10, p = .03) at 5-month follow-up and more severity in the following depressive symptoms: changes in weight and appetite, bodily complaints, and constipation/diarrhea (ß's from .14 to .16, p's from .004 -.03). CONCLUSION: In a primarily Latine and Black trauma patient sample, salivary CRP measured after traumatic injury was related to greater PTSD symptom severity and severity in several depressive symptom clusters. Our preliminary findings suggest that salivary or systemic CRP may be useful to include in models predicting post-trauma psychopathology.

The effect of cognitive behavioural therapy and eye movement desensitization and reprocessing techniques on infertile women: a randomized controlled trial.

RESEARCH QUESTION: What effects do training programmes based on cognitive behavioural therapy (CBT) and eye movement desensitization and reprocessing (EMDR) techniques applied to infertile women affected psychologically and emotionally by infertility have on post-traumatic stress disorder (PTSD) and psychological development? DESIGN: This randomized controlled study was conducted between May 2021 and August 2022. The study population included 90 infertile women referred to the IVF unit of a hospital in a province in eastern Turkey: 30 in the CBT group, 30 in the EMDR group and 30 in the control group. Data were collected using a personal information form, the Subjective Units of Disturbance Scale (SUDS), the Validity of Cognition (VoC) scale, the Infertility Distress Scale (IDS), the Impact of Event Scale-Revised (IES-R) and the Post-traumatic Growth Inventory (PTGI). Women in the experimental groups (CBT and EMDR groups) received the intervention in six sessions over 3 weeks. Pre-tests were administered to both experimental groups and the control group, and post-tests were conducted 3 weeks after the intervention. RESULTS: The mean scores on the SUDS, IDS and IES-R for women in the experimental groups were significantly lower compared with those for women in the control group following the interventions (P < 0.001). The mean scores on the VoC scale and PTGI for women in the experimental groups were significantly higher compared with those for women in the control group following the interventions (P < 0.001). CONCLUSION: The use of CBT and EMDR techniques reduced the negative psychological and emotional effects of infertility among infertile women.

Perpetuating and protective factors in insomnia across racial/ethnic groups of veterans.

Few studies have examined racial/ethnic differences in rates and correlates of insomnia among veterans. This study compared rates of insomnia and interest in sleep treatment among veterans of diverse racial/ethnic backgrounds. Consistent with the 3P model, we tested racial discrimination as a predictor of insomnia, with post-traumatic stress disorder symptoms and romantic partners as perpetuating and protective moderators of this association, respectively. A total of 325 veterans (N = 236 veterans of colour; 12% Asian, 36% Black, 14% Hispanic/Latine) completed questionnaires online from remote locations. Descriptive statistics were used to compare patterns across racial/ethnic groups. Linear regression was used to test moderators of the association between racial discrimination and insomnia severity. Overall, 68% of participants screened positive for insomnia: 90% of Asian; 79% of Hispanic/Latine; 65% of Black; and 58% of White participants. Of those, 74% reported interest in sleep treatment, and 76% of those with partners reported interest in including their partner in treatment. Racial discrimination and post-traumatic stress disorder were correlated with more severe insomnia, while romantic partners were correlated with less severe insomnia. Only post-traumatic stress disorder moderated the association between racial discrimination and insomnia severity. Rates of insomnia were highest among Asian and Hispanic/Latine participants, yet these groups were among the least likely to express interest in sleep treatment. Racial discrimination may exacerbate insomnia symptoms among veterans, but only among those who do not already have disturbed sleep in the context of post-traumatic stress disorder. Romantic partners may serve as a protective factor in insomnia, but do not seem to mitigate the impact of racial discrimination.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Evaluating the Effectiveness of Trauma-Informed Care Frameworks in Provider Education and the Care of Traumatized Patients.

INTRODUCTION: Trauma-informed care (TIC) spans many different health care fields and is essential in promoting the well-being and recovery of traumatized individuals. This review aims to assess the efficacy of TIC frameworks in both educating providers and enhancing care for adult and pediatric patients. METHODS: A literature search was conducted using PubMed, EMBASE, Proquest, Cochrane, and Google Scholar to identify relevant articles up to September 28, 2023. Studies implementing TIC frameworks in health care settings as a provider education tool or in patient care were included. Studies were further categorized based on adult or pediatric patient populations and relevant outcomes were extracted. RESULTS: A total of 36 articles were included in this review, evaluating over 7843 providers and patients. When implemented as a provider education tool, TIC frameworks significantly improved provider knowledge, confidence, awareness, and attitudes toward TIC (P < 0.05 to P < 0.001). Trauma screenings and assessments also increased (P < 0.001). When these frameworks were applied in adult patient care, there were positive effects across a multitude of settings, including women's health, intimate partner violence, post-traumatic stress disorder, and inpatient mental health. Findings included reduced depression and anxiety (P < 0.05), increased trauma disclosures (5%-30%), and enhanced mental and physical health (P < 0.001). CONCLUSIONS: This review underscores the multifaceted effectiveness of TIC frameworks, serving both as a valuable educational resource for providers and as a fundamental approach to patient care. Providers reported increased knowledge and comfort with core trauma principles. Patients were also found to derive benefits from these approaches in a variety of settings. These findings demonstrate the extensive applicability of TIC frameworks and highlight the need for a more comprehensive understanding of their applications and long-term effects.

Impedance cardiogram based exploration of cardiac mechanisms in post-traumatic stress disorder during trauma recall.

Post-traumatic stress disorder (PTSD) is an independent risk factor for developing heart failure; however, the underlying cardiac mechanisms are still elusive. This study aims to evaluate the real-time effects of experimentally induced PTSD symptom activation on various cardiac contractility and autonomic measures. We recorded synchronized electrocardiogram and impedance cardiogram from 137 male veterans (17 PTSD, 120 non-PTSD; 48 twin pairs, 41 unpaired singles) during a laboratory-based traumatic reminder stressor. To identify the parameters describing the cardiac mechanisms by which trauma reminders can create stress on the heart, we utilized a feature selection mechanism along with a random forest classifier distinguishing PTSD and non-PTSD. We extracted 99 parameters, including 76 biosignal-based and 23 sociodemographic, medical history, and psychiatric diagnosis features. A subject/twin-wise stratified nested cross-validation procedure was used for parameter tuning and model assessment to identify the important parameters. The identified parameters included biomarkers such as pre-ejection period, acceleration index, velocity index, Heather index, and several physiology-agnostic features. These identified parameters during trauma recall suggested a combination of increased sympathetic nervous system (SNS) activity and deteriorated cardiac contractility that may increase the heart failure risk for PTSD. This indicates that the PTSD symptom activation associates with real-time reductions in several cardiac contractility measures despite SNS activation. This finding may be useful in future cardiac prevention efforts.

Importance of validity testing in psychiatric assessment: evidence from a sample of multimorbid post-9/11 veterans.

OBJECTIVE: Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures. METHOD: Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures. RESULTS: Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen's d = .60-.69), processing speed (Cohen's d = .68), working memory (Cohen's d = .98), and visual memory (Cohen's d = .88-1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; ß = 0.16; p = .0002), and worse self-reported depression (ß = 0.17; p = .0001), anxiety (ß = 0.15; p = .0007), sleep (ß = 0.10; p = .0233), and functional outcomes (ß = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p's < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91). CONCLUSION: PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Stigma and mental health among people living with HIV across the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Mental health (MH) is extremely relevant when referring to people living with a chronic disease, such as people living with HIV (PLWH). In fact - although life expectancy and quality have increased since the advent of antiretroviral therapy (ART) - PLWH carry a high incidence of mental disorders, and this burden has been exacerbated during the COVID-19 pandemic. In this scenario, UNAIDS has set new objectives for 2025, such as the linkage of at least 90% of PLWH to people-centered, context-specific MH services. Aim of this study was to determine the prevalence of MD in PLWH followed at the Clinic of Infectious Diseases of the University of Bari, Italy. METHODS: From January 10th to September 10th, 2022, all PLWH patients accessing our outpatient clinic were offered the following standardized tools: HAM-A for anxiety, BDI-II for depression, PC-PTSD-5 for post-traumatic stress disorder, CAGE-AID for alcohol-drug abuse. Factors associated with testing positive to the four MD were explored with a multivariable logistic regression model. RESULTS: 578 out of 1110 HIV-patients agreed to receive MH screening, with 141 (24.4%) people resulting positive to at least one MH disorder. HAM-A was positive in 15.8% (n = 91), BDI-II in 18% (n = 104), PC-PTSD-5 in 5% (n = 29) and CAGE in 6.1% (n = 35). The multivariable logistic regression showed a higher probability of being diagnosed with anxiety, depression and post-traumatic stress disorder for PLWH who reported severe stigma, social isolation, psychological deterioration during the COVID-19 pandemic and for those receiving a dolutegravir (DTG)-based regimen. Moreover, history of drug use (OR 1.13; [95% CE 1.06-4.35]), family stigma (2.42 [1.65-3.94]) and social isolation (2.72 [1.55;4.84]) were found to be associated to higher risk for substance use disorder. CONCLUSIONS: In this study, stigma was a strong predictor for being diagnosed of a MH disorder among PLWH. Also, the possible role of dolutegravir as a risk factor for the onset of MH disorders should be considered in clinical practice, and MH of patients receiving DTG-containing regimens should be constantly monitored.

Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.