Fear extinction is foundational to exposure therapy; therefore, the study of strategies to optimize fear extinction is relevant for clinical practice. This article provides a critical review of translational research on pharmacological enhancement of fear extinction, concentrating mostly on d-cycloserine, the agent with the most extensive evidence base across levels of analyses. Despite early promise, results across preclinical, human laboratory, and clinical trials have been mixed. We identify factors that may account for these inconsistent findings, including differences in study design, selection of subjects, sample size, and measurement approaches. We emphasize the need for a rigorous mechanistic research agenda that both assesses extinction processes-acquisition, consolidation, and retrieval-as distinct mechanistic targets and examines the relation between changes in these fear extinction processes and clinical outcomes. Finally, we discuss opportunities to advance translational research in this area by leveraging extant collaborative infrastructures to improve the quality, the efficiency, and ultimately the availability of effective clinical strategies.

Background/Objectives: Trauma-related distress poses significant mental health challenges, with psychotherapy serving as a primary intervention. The Walters Method is a promising new alternative that may help where traditional methods fall short (i.e., in complex or violent cases), but before it can be implemented widely, the existing evidence on the effectiveness of other psychotherapies for trauma-related distress must be mapped to see how and where it relates to other techniques. The aim of this scoping review was to provide an overview of existing evidence on the effectiveness of psychotherapy for trauma-related distress. Methods: A scoping review was conducted to better understand the effectiveness of psychotherapies for trauma-related distress (including PTSD, acute stress disorder, or other serious mental health issues). Results: Thirty-three articles were analysed. Included articles included adults with PTSD, incarcerated women, childbirth trauma survivors, female survivors of sexual abuse, hospitalised COVID-19 patients, adults with serious mental illness, veterans and active soldiers, firefighters, and refugees. Eye Movement Desensitisation and Reprocessing and Cognitive Behavioural Therapy were the most studied and effective treatments. Prolonged Exposure and Narrative Exposure Therapy were less common but noteworthy. Other therapies, including psychodynamic approaches, are seldom studied but have proven effective when explored, highlighting knowledge gaps and potential missed opportunities. Success with these alternative approaches—especially in complex trauma cases like intimate partner violence or child loss where EMDR and CBT may be less effective—suggests they have potential, but further research is needed for validation. Conclusions: This review offers novel contributions to the field by emphasising innovative therapeutic perspectives that extend beyond traditional, more studied, evidence-based approaches such as CBT and EMDR, thereby expanding treatment options for diverse clinical presentations. Alternative therapies show promise, particularly for complex trauma cases like intimate partner violence or child loss where established approaches may be less effective; however, further research is needed to validate their efficacy across diverse populations. Selection of psychotherapy should be based on clients’ goals and comfort, and the cultural and contextual compatibility between the person and intervention. Future research should prioritise underexplored therapies to address current knowledge gaps and improve treatment accessibility for varied clinical needs.

Prolonged Exposure (PE) is an effective evidence-based psychotherapy for posttraumatic stress disorder (PTSD); however, a small subset of veterans fails to achieve meaningful symptom reduction from PE. Given sleep’s role in memory consolidation, poor sleep quality may adversely affect fear extinction learning central to PE. Existing research on sleep and PE response often relies on single-item or global measures that miss nuanced sleep processes, assesses sleep as static (e.g., at baseline) rather than as a dynamic process, or focuses on concurrent rather than prospective associations. This study used a multidimensional measure of sleep quality to evaluate whether changes across several domains of sleep concurrently and prospectively predicted reduced PTSD symptoms. Sleep quality was assessed pre- and post-treatment and PTSD symptoms were measured pre- and post-treatment and at 3- and 6-month follow-ups. Changes in sleep domains were analyzed as predictors of concurrent and prospective PTSD symptoms. Improvements in overall sleep quality, subjective sleep quality, and daytime dysfunction were associated with improvements in PTSD symptom severity from pre- to post-treatment. Greater improvements in overall sleep quality and daytime dysfunction predicted lower PTSD severity at follow-up; however, greater reductions in daytime dysfunction predicted symptom increases across follow-up. Our findings highlight the importance of overall sleep quality in PE response and suggest that daytime dysfunction due to sleep problems may contribute to diminished long-term outcomes. Targeting these aspects of sleep may enhance treatment efficacy.

Can a virtual reality exposure therapy app improve symptoms of Emetophobia? A single-subject Experimental design study.

Is virtual reality always better than 2D videos? A head-to-head randomized controlled trial for fear of flying with long-term follow-up.

Adapting digital anxiety treatments to reduce anorexia nervosa relapse.

Failures in cognitive behavior therapy: The state of the art.

Augmenting in vivo exposure with reward-focused strategies: A randomized controlled trial providing preliminary evidence for improved outcomes in individuals with elevated anhedonia.

Posttraumatic stress disorder (PTSD) presents a significant challenge within the treatment of mental health issues, particularly in veterans and first responders who often experience resistance to standard treatments. This study evaluated the effectiveness of a virtual reality exposure-based treatment with motion as compared to treatment as usual (TAU), as first-line treatment for PTSD within these populations. This multicenter, parallel, single-blind, non-inferiority randomized controlled trial was conducted in three centers across the Netherlands. We included adults diagnosed with occupational or combat-related PTSD, without prior treatment history. Participants were randomized (1:1) to receive either manualized multi-modal motion-assisted memory desensitization and reconsolidation (3MDR) therapy or manualized regular trauma-focused psychotherapy (TAU). 3MDR was applied in fewer sessions than TAU. Primary outcome was self-reported PTSD severity, based on the PTSD Checklist for DSM-5, assessed at baseline, post-treatment, 3 and 6 months post-treatment. Secondary outcomes were clinician-rated PTSD, avoidance, comorbid disorders and symptoms, and functioning. The trial was prospectively registered in the Dutch Trial Register, NL-OMON55588. Between February 15, 2018, and July 22, 2022, 134 participants with PTSD were enrolled, with 67 (50%) randomized to 3MDR and 67 (50%) to TAU of whom 106 (79%) were veterans, and 28 (21%) were first responders. Significant time effects were demonstrated in self-reported and clinician-rated PTSD severity for both groups, as well as in avoidance, comorbid disorders, and functioning. At 6 months post-treatment, 3MDR proved to be non-inferior to TAU in terms of self-reported PTSD (mean difference = -2.91 [95% CI -7.92, 2.10], p = 0.25). 3MDR demonstrates to be an effective alternative first-line treatment for PTSD stemming from occupational traumatic events. Even though it leans on infrastructure with a treadmill and other hardware components, it may offer an alternative over conventional trauma-focused psychotherapies for PTSD that yields savings of a quarter of time spent within therapy.

Joy beyond fear: Positive emotions after exposure in patients with anxiety disorders and their link to threat expectancy and treatment outcome.

Longitudinal network structures in PTSD treatment outcomes: Implications for tailored treatment.

Isradipine enhancement of virtual reality cue exposure therapy is effective for individuals with higher baseline cue-induced craving

Agoraphobic avoidance, fear of situations that seem hard to escape, is common across mental disorders and often remains untreated due to stigma and limited service access. Automated virtual reality (VR) exposure therapy offers a scalable alternative by enabling safe, guided simulations of feared situations. This randomized controlled trial evaluated the efficacy of a culturally adapted version of gameChange VR for reducing agoraphobic avoidance among adults in Hong Kong without psychiatric diagnoses. 272 participants were randomly assigned to either a three-session VR intervention (n = 146) or a waitlist control condition (n = 126). Assessments were conducted at baseline, 3-week, and 1-month follow-ups. Compared to the control condition, participants in the VR intervention condition showed significant reductions in the primary outcome of agoraphobic avoidance (Cohen's d = 0.89), and all the secondary outcomes of agoraphobic distress (d = 1.0), social anxiety (d = 0.91), fear of negative evaluation (d = 0.68), generalized anxiety (d = 0.50), depressive symptoms (d = 0.67), and functional impairment (d = 0.85) at 3 weeks. Significant group differences for all outcomes remained at the 1-month follow-up. Higher baseline levels of agoraphobic symptoms were associated with larger improvements in agoraphobic avoidance. These findings suggest that the automated VR intervention is effective in reducing agoraphobic symptoms in non-clinical populations and appears to be a scalable treatment in Asia where stigma is strong. Future studies could include longer follow-ups and address pandemic-related confounds on avoidance behaviours.

In the shadowed aftermath of trauma, where social bonds fracture and anhedonia calcifies into isolation, oxytocin emerges not merely as a neuropeptide but as a molecular key to reclaiming human connection, yet its therapeutic promise in Post-traumatic stress disorder (PTSD) has long been shackled by profound response heterogeneity. This review unveils the oxytocin receptor gene (OXTR) as the master regulator of this variability, with rs53576 and rs2254298 polymorphisms orchestrating receptor density, synaptic plasticity, and vmPFC-NAcc synchrony in ways that stratify clinical destiny: G-allele carriers, endowed with heightened oxytocin sensitivity, exhibit robust fear extinction and social trust restoration under genotype-guided intranasal oxytocin (IN-OT) augmentation of prolonged exposure therapy, achieving effect sizes rivaling first-line pharmacotherapies; A-allele bearers, by contrast, confront epigenetic silencing and receptor desensitization, demanding escalation to 3,4-Methylenedioxymethamphetamine (MDMA), epigenetic editing, or exosomal delivery. Synthesizing stratified Randomized Controlled Trials (RCTs), functional neuroimaging, and a novel three-tier pharmacogenetic algorithm validated at 78% accuracy across 312 veterans, we chart a precision pathway that transforms oxytocin from probabilistic intervention to predictable recovery heralding routine OXTR genotyping in trauma clinics by 2027 and, ultimately, a future where social reward is no longer a casualty of survival.

In Crohn's disease (CD) patients treated with biologics preoperatively, the optimal strategy for postoperative biologic management remains unclear. This was a retrospective multicenter study involving CD patients with ileocolonic anastomosis from 9 medical centers. Patients were divided into "the consistent group" (postoperative biologic previously used before surgery) and "the switched group" (postoperative biologic not used preoperatively). The primary endpoint was postoperative endoscopic recurrence (ER), which was defined as the first endoscopy performed between 6 and 18 months after surgery. Propensity score matching (PSM) was used to minimize baseline differences between groups, and conditional logistic regression was applied to identify factors associated with ER. In total, 227 patients were included in the study, of whom 177 were in the consistent group. No significant difference was observed in the rate of ER between the switched group and the consistent group (30.0% vs 40.7%, P = .170). In patients with ≤2 risk factors defined by established guidelines, the switched group showed a lower ER rate (20.6% vs 40.0%, P = .038). After 1:1 PSM, the switched group had a lower ER rate (29.4% vs 61.8%, P = .027). Conditional logistic regression analysis revealed that switching biologics was associated with a lower risk of ER (odds ratio = 0.31, 95% confidence interval, 0.11-0.85, P = .023). In CD patients with preoperative biologic exposure, both continuing and switching biologic therapy postoperatively were effective in preventing ER, with switching showing improved endoscopic outcomes after adjustment for confounders.

Written exposure therapy (WET) is a brief, evidence-based treatment for posttraumatic stress disorder (PTSD) that has demonstrated effectiveness in a variety of settings, mostly within the United States. The pilot study described here examined the feasibility, acceptability, and effectiveness of WET in Azerbaijan, where access to evidence-based trauma-focused treatments is limited. Patients diagnosed with PTSD (N = 62) received five weekly sessions of WET delivered by trained clinicians. Self-report measures were used to assess PTSD and depressive symptoms, as well as maladaptive beliefs, at pre- and posttreatment. Working alliance was also assessed using the patient version of the Brief Revised Working Alliance Inventory (BR-WAI). Treatment dropout was low, with only four participants (6.4%) dropping out. Treatment outcome findings indicated that there were significant decreases in PTSD symptoms, d = 1.84; depressive symptoms, d = 1.43; and maladaptive beliefs, d = 0.85. At posttreatment, most (87.1%) participants showed a reliable reduction in PTSD symptoms, and 71.0% met the criteria for clinical recovery. Working alliance moderated PTSD symptom reductions, with stronger agreement on goals and tasks associated with larger reductions in PTSD symptoms, B = -0.18, p =.049. Exploratory analyses revealed that reductions in maladaptive trauma-related beliefs were significantly associated with reductions in PTSD symptoms, B = -0.46, p <.001. Overall, the findings suggest that WET is both feasible and acceptable to implement in Azerbaijan. Moreover, WET was effective, with large treatment effects observed. These findings support the broader implementation of WET in low-resource settings.

The distribution of antimicrobial resistance in major pathogens was analyzed in a tertiary care hospital of Lodhran, Pakistan. Altogether, 1910 patients diagnosed and treated at Shahida Islam Medical Complex Hospital from December 2023 to August 2025 were selected. The antimicrobial resistance of major bacterial and fungal pathogens was quantified, and logistic regression analysis was used to identify the risk factors for infection. Methicillin-resistant Staphylococcus aureus (MRSA) isolates retained susceptibility tovancomycin (58.3%), while ceftazidime/avibactam showed activity against Escherichia coli (80%), Klebsiella pneumoniae (82%), and Pseudomonas aeruginosa (78%). Vancomycin-resistant Enterococcus (VRE) demonstrated resistance to nearly all antibiotics. PCR confirmed TEM and SHV in 23/51 (45%) of E. coli isolates, while in K. pneumoniae TEM and SHV were each detected in 20/35 (56%). Among P.aeruginosa isolates, VIM, NDM, and OXA-48 were each present in 14/37 (37%). The mecA was found in 47/49 (95%) of S. aureus isolates (MRSA), vanA in 34/49 (70%) of S. aureus (VRSA), and vanA in 34/43 (80%) of Enterococcus isolates (VRE). MLST analysis of representative multidrug-resistant isolates identified ST131 (1/3, 33%) among E. coli, ST11 (1/3, 33%) and ST258 (1/3, 33%) among K. pneumoniae, ST175 (1/3, 33%) and ST233 (1/3, 33%) among P. aeruginosa, ST5 (1/3, 33%) and ST22 (1/3, 33%) among S. aureus, and ST17 (1/3, 33%) among Enterococcus spp. PCA revealed distinct clustering of species, with Gram-negatives overlapping, Gram-positives forming separate groups, and fungi clustering independently. Logistic regression identified age ≥65, ICU admission, comorbidities, prior antibiotic exposure, invasive procedures, and immunosuppressive therapy as significant AMR risk factors, while infection control and stewardship reduced risk (P < 0.05). This study demonstrates a high burden of antimicrobial resistance, primarily mediated by TEM and SHV β-lactamases in E. coli and K. pneumoniae, and by VIM, NDM, and OXA-48 carbapenemases in P. aeruginosa. Additionally, MRSA, VRSA, and VRE showed multidrug resistance. Effective infection control and antibiotic stewardship remain critical to limit the spread of resistant pathogens and to reduce hospital-acquired AMR risk.

This study examines the efficacy of virtual reality exposure therapy (VRET) in alleviating foreign language anxiety (FLA) among university students. Although research exists on FLA, interventions have relied on self-reporting measures, leaving a gap in understanding physiological indicators and anxiety reduction. While previous research has explored either the therapeutic potential of virtual reality or the neurophysiological correlations of anxiety through electroencephalography (EEG), few have integrated these methodologies within a single experimental framework. This study combined the foreign language classroom anxiety scale (FLCAS) with (EEG) data to capture subjective and neural responses to anxiety in second language (L2) speaking. The participants (n = 20) completed language speaking tasks both before and after VR intervention, which exposed them to anxiety-inducing conditions replicating language challenges. During these tasks, brainwave signals were recorded, focusing on frontal alpha asymmetry (FAA) and alpha power (F3, F4), indicating neural activity associated with stress and emotional regulation. Results showed participants experienced a significant decrease (p = 0.017 &lt; 0.05) in self-reported FLCAS scores after VRET. The reduction in FLA showed a negative correlation with increased alpha power at F3 (r = −0.55, p = 0.012), suggesting a link between left frontal neural regulation and anxiety reduction. These findings underscored VRET’s effectiveness in influencing emotional responses during L2-speaking tasks.

Abstract Background The intrauterine device (IUD) is an effective form of birth control, but its utilization worldwide is low due to discomfort and anxiety during insertion. Virtual reality (VR) technology shows promise in reducing pain during IUD insertion. Aim &amp; objectives This study aims to evaluate the efficacy of VR technology exposure in reducing pain associated with IUD insertions. Search strategy We comprehensively searched Midline, Scopus, Web of Science, and Cochrane Library from inception to April 2024 to include all studies assessing the efficacy of VR integration during IUD insertion. Selection criteria We selected randomized controlled trials that investigate the benefits of VR technology on women undergoing IUD insertion. Data collection and analysis The primary study endpoint was the degree of pain during IUD insertion assessed by the Visual Analogue Scale (VAS). Quality evaluation for included studies was done using the Cochrane Risk of Bias assessment. Results Our search strategy revealed 531 search results. Four clinical trials enrolling 315 women were found adherent to our preselected eligibility criteria. We found a significant reduction in the degree of pain during IUD insertion in the VR group compared to the standard practice group (SMD= -1.69, 95% CI: [-3.20,-0.18]; P= 0.03). None of the meta-analyses for the patients’ anxiety during IUD insertion or post-insertion satisfaction showed statistical significance between the two study groups. Conclusion VR technology demonstrated a notable decrease in pain during IUD insertion compared to standard practice, while no significant differences were observed in patients' anxiety or post-insertion satisfaction between the study groups.

Extended reality (XR) encompasses various immersive technologies that enhance perception with virtual elements. Previous research has focused in particular on virtual reality-assisted exposure therapy but there are currently dynamic developments in terms of both content and structure of XR research for psychotherapy. This narrative review describes content-related, technical and structural developments in the research of XR applications for psychotherapy, as identified by members of the Extended Reality for Psychotherapy network. The use of mixed reality technologies and artificial intelligence was mentioned as well as the development and testing of creative therapeutic concepts beyond the classical exposure paradigm. In addition, structural developments, such as the establishment of standardized processes, the professionalization of development, barriers to implementation in healthcare practice and regulatory aspects are outlined. The experts point to technical advances and emerging innovative concepts that would not be feasible in the current psychotherapy. Given the complex technology, which must simultaneously meet multiple regulatory requirements, broad-based interdisciplinary research is needed.