Motion-assisted multi-modal memory desensitization and reconsolidation (3MDR) has emerged as a promising advancement in exposure-based therapies, particularly for treatment-resistant posttraumatic stress disorder (PTSD) and related disorders. Integrating treadmill-assisted movement with personalized trauma-related imagery and guided narrative processing, 3MDR promotes emotional engagement and supports memory reconsolidation in ways that traditional therapies often fail to achieve. This article reviews key developments in 3MDR's evolution, validation, and implementation. Randomized controlled trials in the Netherlands, the United Kingdom, the United States, and Canada have demonstrated significant reductions in PTSD symptoms, improved emotional processing, and strong patient adherence. Originating from the Computer-Assisted Rehabilitation Environment system - initially designed for physical rehabilitation - 3MDR was adapted to overcome avoidance and disengagement frequently seen in Veterans and other trauma-exposed groups. Technological improvements, including enhanced software usability, high-definition immersive visuals, and real-time customization, have strengthened its therapeutic impact. Recent expansions include pilot applications for adolescents, moral injury, and complex PTSD, supported by a structured international training framework requiring supervised cases and ongoing coaching through the International Consortium of 3MDR. Emerging innovations, such as HoloLens-based delivery, are also being explored. While acceptance among patients and clinicians is strong, broader adoption will require sustained investment in infrastructure and workforce training.

Posttraumatic stress disorder (PTSD) is a complex disorder that often persists despite the use of evidence-based treatments. This systematic review aims to synthesize existing definitions of treatment-resistant PTSD (TR-PTSD) and examine the criteria used across studies to inform future research and clinical guidelines.

A systematic search was conducted in four databases. Studies were included if they reported on adult participants with TR-PTSD, regardless of definition, or described non-response to one or more treatments. A narrative synthesis was used to categorize findings and suggest refinements to a working TR-PTSD definition.

Of 4,046 screened articles, 55 studies met the inclusion criteria. We found substantial variation in how TR-PTSD was defined across studies. Studies investigated pharmacological (n = 19), psychosocial (n = 16), psychedelic-assisted (n = 7), and emerging treatments (n = 13). Findings highlighted diverse intervention strategies. Some reduced PTSD symptoms significantly, and others showed mixed or limited efficacy.

This study consolidates existing research on TR-PTSD, revealing significant variability in its definitions across studies. The lack of standardized criteria underscores the need for a more consistent framework to guide research and clinical decision-making. The authors propose a dynamic reassessment of treatment resistance that considers adherence, treatment delivery, comorbidities, and mechanisms of action. Future research should incorporate a broader range of treatment response indicators, such as biomarkers and clinical subtypes, to establish a standardized model for TR-PTSD. A clearer definition will improve patient care, aid in therapy selection, and support the development of more effective treatments.

Although clinical practice guidelines (CPG) emphasize several trauma-focused therapies for posttraumatic stress disorder (PTSD) as effective, many persons with PTSD do not experience full recovery, particularly among military and Veteran populations, leading to some individuals being labelled as having treatment-resistant PTSD (TR-PTSD). Recent advancements in neuroscience have enhanced the understanding of PTSD as a disorder driven by dynamic brain networks that contribute to core PTSD symptomatology, dissociation, moral injury, and systemic symptoms, thus highlighting the need for neuroscientifically informed interventions that address PTSD as it is expressed mentally, bodily, and neurally.

This report reviews emerging PTSD interventions guided by neuroscientific advancements, specifically deep brain reorienting (DBR), virtual reality integrative therapy (VRIT), neurofeedback (NFB), and non-invasive brain stimulation (NIBS), as means to augment interventions recommended in CPG.

Each of DBR, VRIT, NFB, and NIBS show promise as neuroscience-informed therapies to augment outcomes of psychotherapies recommended in CPG by directly targeting some of the mind-body-brain mechanisms underlying PTSD symptoms.

The concept of TR-PTSD should be re-evaluated in light of new therapeutic approaches. Consistent with professional practice guidelines, neuroscientifically informed interventions such as DBR, VRIT, NFB, and NIBS offer a path toward more effective, individualized treatment by augmenting outcomes associated with CPG for PTSD by modulating mind-body-brain connections.

There are high rates of co-occurring posttraumatic stress disorder (PTSD) and alcohol use among women Veterans. Given the growing number of midlife women Veterans utilizing Veterans Health Administration (VHA) care and their unique stressors, the purpose of the current study was to examine the unique relationships between PTSD symptom clusters and alcohol use among this group of women.

Fifty treatment-seeking midlife women Veterans (M _age = 50.00; 72% Black/African American) completed self-report measures on demographics, alcohol use and behaviours, and PTSD symptoms as part of their intake at a Veterans Affairs (VA) general mental health clinic.

Findings indicated that alcohol use was associated with PTSD symptom severity, as well as the intrusions, negative cognitions and mood, and arousal PTSD symptom clusters, but not the avoidance PTSD symptom cluster, after accounting for branch of service.

Findings of the current study are in line with previous research highlighting the unique relationship between alcohol use and PTSD symptoms. Our sample was primarily Black/African American midlife women, which may limit the generalizability of our findings. Given high rates of alcohol use and mental health symptoms among women at midlife, providers and researchers alike should aim to better understand the intersection of perimenopause/menopause and mental health outcomes to provide comprehensive health care for at-risk Veterans.

The study aimed to quantify types of premature treatment termination in a psychosomatic hospital and to investigate if patient characteristic at the beginning of inpatient or day-clinic treatment can predict a subsequent premature termination.

Routine clinical data were analysed retrospectively for N = 2017 patients. Based on treatment length and medical discharge reports, patients were categorized as premature treatment termination related to therapeutic reasons (PTT-T) or not (NPTT-T) by two independent raters. Next, two prediction models were built using random forest algorithms. Model 1 included general clinical information, model 2 additional data from self-report measures at treatment admission. Finally, a SHAP feature importance plot was calculated for each model.

In this study, 12.1% of the patients ended treatment prematurely related to therapeutic reasons. Model 1 predicted 29% of PTT-Ts and 95% of NPTT-Ts in the holdout sample correctly. Model 2 was able to identify 59% of PTT-Ts and 80% of NPTT-Ts. The absence of self-report measures at admission was the predictor variable with the greatest influence.

PTT-T in inpatient treatment can substantially be predicted by routine clinical intake data, which can therefore provide a valuable source for identifying patients at risk.

Dementia is a progressive neurodegenerative condition, yet it is frequently under-recognised as terminal, contributing to delayed or inadequate end-of-life care. Accurate prognostication in advanced dementia is essential to support timely palliative interventions. However, prognostic uncertainty remains high, and existing tools are inconsistently validated.

To identify and review current prognostic models designed for survival estimation of people with advanced dementia.

Systematic review prospectively registered on PROSPERO, supported by a narrative synthesis of key findings.

MEDLINE, Embase, CINAHL, and PsycINFO were searched from inception to April 2025, alongside grey literature sources. Eligible studies reported development or validation of prognostic models estimating survival in advanced dementia. Risk of bias was appraised using PROBAST, and certainty of evidence using GRADE guidelines.

Six prognostic tools were identified across seven studies, including 225,553 individuals with advanced dementia across community, hospital, and nursing home settings. Key prognostic indicators included demographic factors, comorbidities, and functional dependency. Reported AUC values ranged from 0.55 to 0.76. The PRO-MADE model demonstrated the highest discrimination (AUC 0.76) and was the only tool to report detailed calibration metrics, though external validation showed reduced performance. Five studies demonstrated high risk of bias due to methodological limitations and lack of external validation.

Current prognostic tools for advanced dementia show limited and inconsistent accuracy and should not be used in isolation. Further research should focus on robust external validation across various countries and healthcare settings before one model can be recommended for widespread application.

Clinical guidelines aid decision-making, but their simplifying strength becomes a limitation in complex, value-laden situations. Once meant to summarise evidence, they now function as prescriptive standards used in quality and legal assessments. Overly rigid directives can undermine autonomy, hide uncertainty and restrict clinical judgement. Using complexity science and 'wicked problem' theory, we introduce 'wicked complexity' to better match guidelines design to real clinical challenges. Applying this to deprescribing psychoactive drugs, we show how traditional, adherence-focused guidance can prompt defensive practice. Guidelines for wicked complexity should instead clarify risks, support moral deliberation and support shared, iterative decision-making across healthcare.

To document and characterize headache and dizziness provocation during mental imagery of real-life symptom-provoking movements in patients with persistent postconcussive symptoms (PPCS).

Outpatient rehabilitation department at Reuth Rehabilitation Hospital, Tel Aviv, Israel.

Thirteen adults (7 females; mean age 34.3 ± 12.6 years) undergoing multidisciplinary rehabilitation for PPCS with functional decline after mild traumatic brain injury. All were ≥3 months postinjury, reported both headache and dizziness, and had a known real-life symptom trigger (eg, movements, activity). Patients with cognitive, linguistic, or psychiatric impairments were excluded.

Case series.

The primary outcome was the result of mental imagery testing of symptom-provoking movements for headache and dizziness, routinely performed as part of vestibular evaluation protocol at the facility. Secondary outcomes included demographics, medical history, clinical trajectory, imaging results, current medications, symptom questionnaires scores (Brief Pain Inventory, Dizziness Handicap Inventory), and vestibular bedside assessments findings.

Headache was provoked in 9 out of 13 patients (69.2%), and dizziness in 11 out of 13 patients (84.6%) during mental imagery of real-life symptom-provoking movements. Five of the 13 patients (38.5%) had oculomotor and vestibular abnormalities (eg, benign paroxysmal positional vertigo, vestibular asymmetry, oculomotor deficits). Symptom reproduction occurred regardless of vestibular pathology in 3 out of 5 cases with oculomotor or vestibular abnormalities. All patients reported additional symptoms, such as musculoskeletal pain, fatigue, and sleep disturbances.

This case series identifies a novel clinical phenomenon in patients with PPCS, where mental imagery of symptom-provoking movements provokes headache and dizziness. These findings suggest a potential link between mental imagery and symptom exacerbation, supporting the notion that PPCS may reflect functional rather than structural mechanisms. This perspective underscores the need for further research to elucidate underlying mechanisms and explore potential therapeutic interventions.

Limitations of current classifications of schizophrenia, schizoaffective disorder, and bipolar disorder are evident from their overlapping symptoms, aetiologies, treatments, and outcomes, and present a barrier to novel treatment discovery. Alternative conceptualisations are needed to address nosological validity, align diagnosis to aetiology, and improve prognostication and treatment choice. We aimed to identify latent classes across the psychosis spectrum based on premorbid functioning and outcomes, and assess these in relation to genetic liability and symptom dimensions.

Participants with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder type 1, were ascertained from four UK clinical cohorts (total n=5,043). Latent class analysis was conducted using phenotypes not included within the diagnostic criteria, including premorbid functioning, age at illness onset, and measures of severity and course. Polygenic scores (PGS) for psychiatric disorders and behavioural traits were tested for associations with latent classes. We tested if diagnosis explained associations between PGS and classes.

A three-class model provided the best fit. Class one had poorer premorbid functioning, lower rates of recovery, and higher PGS for schizophrenia and ADHD. Class three had the highest functioning, higher rates of psychosocial stressors before onset, higher intelligence PGS and lower PGS for psychiatric disorders. Class two was intermediate between classes one and three on measures of functioning, but was characterised by high levels of involuntary hospital admissions and high bipolar disorder PGS. Diagnosis only partially explained associations between PGS and class membership.

We identified classes across the psychosis spectrum characterised by different premorbid functioning and outcomes, that cut across diagnostic categories and captured genetic liability not explained by diagnosis. Our findings suggest alternative conceptualisations of psychotic disorders may complement diagnoses in mapping to the aetiology of these conditions, and could be useful to advance precision psychiatry.

When confronted with negative events, regulating emotions is essential for self-management and mental health. Temporal lobe epilepsy (TLE) patients, particularly right TLE (rTLE) patients, show altered responses towards emotional stimuli. However, neural correlates of emotion regulation and its interplay with stimulus-based emotion processing have not been studied in TLE so far. Therefore, we compared functional MRI activity during up- and downregulation of emotions towards negative scenes among 21 left TLE and 18 rTLE patients, 18 frontal lobe epilepsy (FLE) patients and 17 healthy controls. To assess stimulus-based processing, participants were asked to permit their feelings towards negative or neutral pictures. Voxel-based analyses were complemented by network-based analyses, as epilepsy is a network disorder. During stimulus-based emotion processing, rTLE patients displayed less activation compared to all other groups. Regions of reduced activity were mostly part of the frontoparietal control network and the default mode network (both P _FDR < 0.05) and included the frontal pole, the superior frontal gyrus, parietal regions and the cerebellum (all P _FWE < 0.05). Activation patterns during emotion regulation were highly similar between controls and left TLE and rTLE patients. Direct group comparisons revealed that during upregulation of emotions, controls and left TLE patients displayed higher activity than FLE patients in areas of the left default mode network (all P _FWE < 0.05). Our results dovetail with previous findings of diminished activity towards aversive stimuli in rTLE and show that in the same patients, neural underpinnings of emotion regulation are intact. In contrast, FLE patients displayed the opposite pattern with a largely intact response to aversive stimuli but disrupted neural underpinnings of emotion regulation, pointing to a double dissociation between rTLE and FLE.