Increasing attention has been recently devoted to treatment-resistant depression (TRD); however, its clinical characteristics, potential risk factors, and course are still debated. Most recently, childhood trauma exposure has been correlated to TRD, but systematic investigation on the role of lifetime trauma is still lacking. The aim of this paper was to revise current evidence on early and recent trauma exposure in TRD.

A systematic search was conducted from the 1st of June to the 20th of February 2024 in accordance with the PRISMA 2020 guidelines and using the electronic databases PubMed, Web of Science, and Embase.

The primary database search produced a total of 1998 record, and finally, the search yielded a total of 22 publications, including 18 clinical studies, 3 case reports, and 1 case series, all from the period 2014 to 2024.

Limitations include a small sample size of some studies and the lack of homogeneity in the definition of TRD. Furthermore, we only considered articles in English, we excluded preprints or abstracts, and we included case reports.

This review highlights the role of early and recent trauma in TRD, even in the absence of a full-blown post-traumatic stress disorder (PTSD), highlighting the need for a thorough assessment of trauma in patients with TRD and of its role as a therapeutic target.

Economic variables such as socioeconomic status and debt are linked with an increased risk of a range of mental health problems and appear to increase the risk of developing of post-traumatic stress disorder (PTSD). Previous research has shown that people living in more deprived areas have more severe symptoms of depression and anxiety after treatment in England’s NHS Talking Therapies services. However, no research has examined if there is a relationship between neighbourhood deprivation and outcomes for PTSD specifically. This study was an audit of existing data from a single NHS Talking Therapies service. The postcodes of 138 service users who had received psychological therapy for PTSD were used to link data from the English Indices of Deprivation. This was analysed with the PCL-5 measure of PTSD symptoms pre- and post-treatment. There was no significant association between neighbourhood deprivation measures on risk of drop-out from therapy for PTSD, number of sessions received or PTSD symptom severity at the start of treatment. However, post-treatment PCL-5 scores were significantly more severe for those living in highly deprived neighbourhoods, with lower estimated income and greater health and disability. There was also a non-significant trend for the same pattern based on employment and crime rates. There was no impact of access to housing and services or living environment. Those living in more deprived neighbourhoods experienced less of a reduction in PTSD symptoms after treatment from NHS Talking Therapies services. Given the small sample size in a single city, this finding needs to be replicated with a larger sample.

1. (1) Previous literature has shown that socioeconomic deprivation increases the risk of a range of mental health problems.

2. (2) Existing research suggests that economic variables such as income and employment are associated with greater incidence of PTSD.

3. (3) In the current study, those living in more deprived areas experienced less of a reduction in PTSD symptoms following psychological therapy through NHS Talking Therapies.

4. (4) The relatively poorer treatment outcomes in the current study are not explained by differences in baseline PTSD severity or drop-out rates, which were not significantly different comparing patients from different socioeconomic strata.

Adverse childhood experiences (ACEs) have been associated with increased risks of autoimmune diseases. However, data are scarce on the role of specific ACEs as well as the potential mediating role of adverse mental health symptoms in this association.

A cohort study using the nationwide Icelandic Stress-And-Gene-Analysis (SAGA, 22,423 women) cohort and the UK Biobank (UKB, 86,492 women) was conducted. Participants self-reported on five ACEs. Twelve autoimmune diseases were self-reported in SAGA and identified via hospital records in UKB. Poisson regression was used to assess the cross-sectional association between ACEs and autoimmune diseases in both cohorts. Using longitudinal data on self-reported mental health symptoms in the UKB, we used causal mediation analyses to study potential mediation by depressive, anxiety, and PTSD symptoms in the association between ACEs and autoimmune diseases.

The prevalence of ACEs was 50% in SAGA and 35% in UKB, while the prevalence of autoimmune diseases was 29% (self-reported) and 14% (clinically confirmed), respectively. In both cohorts, ACEs were associated with an increased prevalence ratio (PR) of any studied autoimmune disease in a dose–response manner (PR = 1.10 (95%CI = 1.08–1.12) per ACE), particularly for Sjögrens (PR = 1.34), polymyalgia rheumatica (PR = 1.20), rheumatoid arthritis (PR = 1.14), systemic lupus erythematosus (PR = 1.13), and thyroid disease (PR = 1.11). Sexual abuse and physical and emotional neglect were consistently associated with an elevated prevalence of autoimmune diseases when including all ACEs in the model. Approximately one fourth of the association was mediated through depression, anxiety, and PTSD.

These findings based on two large cohorts indicate a role of ACEs and corresponding mental health distress in autoimmune diseases among adult women.

Cognitive behavioural therapy (CBT) and eye-movement desensitisation and reprocessing (EMDR) are NICE-recommended evidence-based treatments for post-traumatic stress disorder (PTSD). However, there is less specification of which individuals might find CBT versus EMDR more effective, or whether other factors influence treatment outcomes. This study describes a service evaluation of trauma-focused CBT (CT-PTSD) and EMDR treatment outcomes for PTSD in a London out-patient NHS Talking Therapies (NHS TT) service over 11 years (N=1580). The evaluation was conducted in an adult sample (mean age 37 years), of which 65% were women. The mean number of treatment episodes for PTSD in the service in the sample was 2.39 (SD=1.86), and the mean number of therapy sessions attended was 6.15 (SD=6.43). When using NHS TT recovery criteria, there was no significant difference between PTSD recovery rates in the service for those who received CT-PTSD (40.8%) versus EMDR (43.6%). CT-PTSD was associated with greater reductions in anxious and depressive (but not PTSD-specific) symptoms than EMDR, but this was confounded by the fact that individuals receiving CT-PTSD in the service had higher anxiety and depression scores at start-of-treatment. Older age and non-female gender were associated with higher anxiety and depression scores. PTSD recovery rates were comparable to other NHS TT services. There is no clear indication that either CBT or EMDR is a more effective treatment for PTSD symptoms in the service, although preliminary findings could inform treatment planning regarding differential effects of the treatments on anxious and depressive symptoms. Other clinical implications are discussed.

1. (1) To gain a better understanding of the relative effectiveness of trauma-focused CBT and EMDR for PTSD, as provided in a working NHS TT service.

2. (2) To allow better-informed clinical and treatment pathway planning for individuals with trauma problems in a talking therapies service.

3. (3) To contribute to the wider research literature on effective interventions for trauma within cognitive therapy and NHS frameworks.

Post-traumatic stress disorder (PTSD) is characterized by severe distress and associated with cardiometabolic diseases. Studies in military and clinical populations suggest that dysregulated metabolomic processes may be a key mechanism. Prior work identified and validated a metabolite-based distress score (MDS) linked with depression and anxiety and subsequent cardiometabolic diseases. Here, we assessed whether PTSD shares metabolic alterations with depression and anxiety and if additional metabolites are related to PTSD.

We leveraged plasma metabolomics data from three subsamples nested within the Nurses’ Health Study II, including 2835 women with 2950 blood samples collected across three time points (1996–2014) and 339 known metabolites assayed by mass spectrometry-based techniques. Trauma and PTSD exposures were assessed in 2008 and characterized as follows: lifetime trauma without PTSD, lifetime PTSD in remission, and persistent PTSD symptoms. Associations between the exposures and the MDS or individual metabolites were estimated within each subsample adjusting for potential confounders and combined in random-effects meta-analyses.

Persistent PTSD symptoms were associated with higher levels of the previously developed MDS. Out of 339 metabolites, we identified 29 metabolites (primarily elevated glycerophospholipids and glycerolipids) associated with persistent symptoms (false discovery rate < 0.05; adjusting for technical covariates). No metabolite associations were found with the other PTSD-related exposures.

As the first large-scale, population-based metabolomics analysis of PTSD, our study highlighted shared and distinct metabolic differences linked to PTSD versus depression or anxiety. We identified novel metabolite markers associated with PTSD symptom persistence, suggesting further connections with metabolic dysregulation that may have downstream consequences for health.

Crowd crush disasters result in psychological risks such as anxiety, depression, and post-traumatic stress disorder (PTSD). This descriptive research study identified the mental health status of Koreans after the Itaewon crowd crush disaster and explored related factors.

Data were collected May 2-9, 2023 using an online survey. Participants included 205 adults aged 19-69 years recruited through South Korean local and online university communities. Their mental health and related factors were measured at 6 months post-disaster. Data were analyzed using IBM® SPSS® Statistics 26.0. and R 3.4.2.

Significant differences in anxiety, depression, and PTSD among participants who experienced the disaster as victims; changes in drinking frequency and alcohol consumption; and differences in anxiety and PTSD according to family type were observed. Comparing the 3 and 6 month surveys, there were no significant changes in anxiety, depression, PTSD, general mental health, or mental well-being. When mental health severity was divided according to victimization, a significant difference in the severity of anxiety, depression, and PTSD was observed.

Participants’ levels of anxiety, depression, and PTSD varied according to their direct and indirect experience of the disaster, with higher levels of PTSD even without direct experience with the disaster.

This research aimed to comprehensively explore the impact of diverse challenges encountered by older adults on the development of post-traumatic stress disorder (PTSD). It delved into how these effects vary depending on individuals’ levels of trust in authority and medical professionals, providing a nuanced understanding of the interplay between external challenges, personal trust, and mental health outcomes in the older population.

The COVID-19 pandemic has imposed significant hardships, particularly on the ageing population, with potential psychological repercussions such as PTSD. Notably, there is a dearth of research exploring this association within the context of Chinese older adults, a group that may experience unique impacts due to cultural differences in the face of global crises.

Data were collected from a representative sample of 1,211 participants aged 60 years and above in Shenzhen. Logistic and hierarchical linear regression methods were utilized to investigate the relationship between the challenges posed by COVID-19, public trust, and the manifestation of PTSD symptoms.

Higher levels of challenges related to ‘supplies, services access and safety’, ‘abuse and conflicts’, and ‘anger and fear’ were associated with PTSD. Furthermore, a lower level of challenges related to ‘disease management and information’ was associated with PTSD. Trust in authority or medical professionals was the moderator between the challenges brought about by COVID-19 and PTSD, which helped to lower the impact of challenges. Despite the challenges brought by COVID-19 to people, nurturing a stronger sense of trust in authority and medical professionals would ease older adults’ psychological stress and concerns.

Psychological reactions in response to disasters have been associated with increased mental health (MH) symptomatology, decreased quality of life (QOL), and post-traumatic stress (PTSD). This study provides a rare opportunity to examine post disaster MH longitudinally in a sample of adolescents.

From 2018-20, adolescents (12-18 years, N=228) were interviewed about disaster exposure, QOL using the Adolescent Quality of Life-Mental Health Scale (AQOL-MHS), psychological symptoms, and diagnoses.

Having an MH diagnosis and PTSD are clear indicators of worse Emotional Regulation (ER) (P ≤ 0.03, P ≤ 0.0001) and Self-Concept (SC) (P ≤ 0.006, P ≤ 0.002) QOL. Girls were disproportionately affected in all models for SC and Social Context domains (P ≤ 0.0001, P ≤ 0.01). Interaction models results for ER (P ≤ 0.05) and SC (P ≤ 0.01) indicate that those with PTSD are improving over time at a greater rate than those without PTSD.

Recovery takes time and a clear sex disparity for girls was observed. Results for the different AQOL-MHS domains highlight how the challenges experienced by disasters are multifaceted. Knowing who is at greater risk can allow for better resource allocation and targeted population-based prevention strategies to promote and maintain MH and resolve risk factors for mental illnesses.

Given the US population concentration near coastal areas and increased flooding due to climate change, public health professionals must recognize the psychological burden resulting from exposure to natural hazards.

We performed a systematic search of databases to identify articles with a clearly defined comparison group consisting of either pre-exposure measurements in a disaster-exposed population or disaster-unexposed controls, and assessment of mental health, including but not limited to, depression, post-traumatic stress (PTS), and anxiety.

Twenty-five studies, with a combined total of n =616 657 people were included in a systematic review, and 11 studies with a total of 2012 people were included in a meta-analysis of 3 mental health outcomes. Meta-analytic findings included a positive association between disaster exposure and PTS (n = 5, g = 0.44, 95% CI 0.04, 0.85), as well as depression (n = 9, g = 0.28, 95% CI 0.04, 0.53), and no meaningful effect size in studies assessing anxiety (n = 6, g = 0.05 95% CI −0.30, 0.19).

Hurricanes and flooding were consistently associated with increased depression and PTS in studies with comparison groups representing individuals unaffected by hazards.

Cognitive therapy for PTSD (CT-PTSD) is an efficacious treatment for children and adolescents with post-traumatic stress disorder (PTSD) following single incident trauma, but there is a lack of evidence relating to this approach for youth with PTSD following exposure to multiple traumatic experiences.

To assess the safety, acceptability and feasibility of CT-PTSD for youth following multiple trauma, and obtain a preliminary estimate of its pre–post effect size.

Nine children and adolescents (aged 8–17 years) with multiple-trauma PTSD were recruited to a case series of CT-PTSD. Participants completed a structured interview and mental health questionnaires at baseline, post-treatment and 6-month follow-up, and measures of treatment credibility, therapeutic alliance, and mechanisms proposed to underpin treatment response. A developmentally adjusted algorithm for diagnosing PTSD was used.

No safety concerns or adverse effects were recorded. Suicidal ideation reduced following treatment. No participants withdrew from treatment or from the study. CT-PTSD was rated as highly credible. Participants reported strong working alliances with their therapists. Data completion was good at post-treatment (n=8), but modest at 6-month follow-up (n=6). Only two participants met criteria for PTSD (developmentally adjusted algorithm) at post-treatment. A large within-subjects treatment effect was observed post-treatment and at follow up for PTSD severity (using self-report questionnaire measures; ds>1.65) and general functioning (CGAS; ds<1.23). Participants showed reduced anxiety and depression symptoms at post-treatment and follow-up (RCADS-C; ds>.57).

These findings suggest that CT-PTSD is a safe, acceptable and feasible treatment for children with multiple-trauma PTSD, which warrants further evaluation.

Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.

Migraine and post-traumatic stress disorder (PTSD) are both twice as common in women as men. Cross-sectional studies have shown associations between migraine and several psychiatric conditions, including PTSD. PTSD is disproportionally common among patients in headache clinics, and individuals with migraine and PTSD report greater disability from migraines and more frequent medication use. To further clarify the nature of the relationship between PTSD and migraine, we conducted bidirectional analyses of the association between (1) migraine and incident PTSD and (2) PTSD and incident migraine.

We used longitudinal data from 1989–2020 among the 33,327 Nurses’ Health Study II respondents to the 2018 stress questionnaire. We used log-binomial models to estimate the relative risk of developing PTSD among women with migraine and the relative risk of developing migraine among individuals with PTSD, trauma-exposed individuals without PTSD, and individuals unexposed to trauma, adjusting for race, education, marital status, high blood pressure, high cholesterol, alcohol intake, smoking, and body mass index.

Overall, 48% of respondents reported ever experiencing migraine, 82% reported experiencing trauma and 9% met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for PTSD. Of those reporting migraine and trauma, 67% reported trauma before migraine onset, 2% reported trauma and migraine onset in the same year and 31% reported trauma after migraine onset. We found that migraine was associated with incident PTSD (adjusted relative risk [RR]: 1.26, 95% confidence interval [CI]: 1.14–1.39). PTSD, but not trauma without PTSD, was associated with incident migraine (adjusted RR: 1.20, 95% CI: 1.14–1.27). Findings were consistently stronger in both directions among those experiencing migraine with aura.

Our study provides further evidence that migraine and PTSD are strongly comorbid and found associations of similar magnitude between migraine and incident PTSD and PTSD and incident migraine.

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in posttraumatic stress disorder (PTSD), and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated.

Trauma-exposed individuals (n = 113) underwent a 2-day fear conditioning and extinction protocol. Conditioning and extinction learning phases were followed by extinction recall 24 h later. The association of extinction recall with REM characteristics and REM vagal activity (indexed as heart rate variability) during the intervening consolidation night was examined.

Consistent with our hypotheses, REM disruption was associated with poorer physiological and explicit extinction memory. Furthermore, higher vagal activity during REM was associated with better explicit extinction memory, and physiological extinction memory in males.

These findings support the notion that abnormal REM, including reduced REM vagal activity, may contribute to PTSD by impairing the consolidation of extinction memory.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions—TBI history, PTSD, and vascular risk—and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition.

We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance.

Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p’s >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p’s <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052).

Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.