This study assessed empathy in clinically stable individuals with SCZ and their first-degree relatives (FDRs).

Empathy, comprising cognitive and affective components, is impaired in schizophrenia (SCZ) and influences functional outcomes.

Thirty individuals with SCZ, their unaffected siblings (n = 30) and matched healthy controls (HCs) participated through purposive sampling. Participants completed the multifaceted empathy test (MET) task, which evaluates both cognitive empathy (CE) and emotional empathy (EE).

Individuals with SCZ scored significantly lower than both FDR and HC on measures of positive (η_p ² = 0.25), negative (η_p ² = 0.15), and composite (η_p ² = 0.27) CE, unlike previous studies. Correlation analysis for individuals with SCZ showed that composite EE was significantly correlated with composite CE.

CE, but not EE, is significantly impaired in individuals with SCZ in remission. This deficit is related to the duration of the illness.

In India, the rights of persons with disabilities (RPwD) Act, 2016, aims to ensure dignity, equality, and autonomy for persons with disabilities, and sets out guidelines for the assessment and certification of various disabilities. Among the disabilities covered under the Act, several critical gaps have been consistently noted in the assessment and certification of specific learning disabilities (SLD) and intellectual impairment-related conditions. These include the rigid application of intelligence quotient (IQ) criterion in SLD assessment, as well as the difficulties in evaluating adults who may have SLD but were never formally diagnosed during childhood. In addition, persons with borderline intellectual functioning (BIF) are often overlooked, as this condition is not recognized as a benchmark disability. Against this backdrop, the present paper proposes changes needed in the RPwD Act Guidelines for assessing and certifying these conditions. To provide context, it first reviews how current diagnostic systems conceptualize SLD and BIF, and traces the major shifts in these conceptualizations over time that inform current understanding.

Nitazenes, a highly potent class of synthetic opioids, have emerged in Canadian unregulated drug markets. We report on their presence and composition, along with overdose trends.

Samples were obtained from January 2019 to July 2024 from two drug checking services (Toronto's Drug Checking Service (TDCS) and drug checking partners affiliated with the British Columbia Centre on Substance Use (BCCSU)) and national police seizure data from Health Canada's Drug Analysis Service (HC-DAS). Overdose data were retrieved from the Office of the Chief Coroner for Ontario from January 2019 to December 2022 and included deaths in which a nitazene was present. We conducted Cochran-Armitage test and logistic regression trend analyses to assess trends over time.

Of 668,486 samples, 4074 (0.61%) contained nitazenes: 532 from drug checking services (489 (0.07%) from TDCS; 43 (0.01%) from BCCSU) and 3542 (0.53%) from police seizures (HC-DAS). Twelve unique nitazenes were detected. Common co-occurring drugs included caffeine, benzodiazepine-related drugs and fentanyl and fentanyl-related drugs. Nitazenes were expected in 3 (< 1%) of 532 drug checking samples. Of 14,103 samples from TDCS, 886 (6.28%) were associated with an overdose, among which 76 (8.58%) contained nitazenes. Of 8719 opioid deaths in Ontario and 1803 in Toronto, nitazenes were present in 79 (0.91%) and 33 (1.83%), respectively. Significant trends (p < 0.001) in nitazene detections and overdoses in Toronto, as well as nitazene detections across Canada, were observed, increasing prior to and peaking in January-March 2022, followed by reductions.

The presence of nitazenes in Canada requires enhanced overdose prevention responses and drug market monitoring.

DNM1L-related disorders are rare mitochondrial diseases characterized by defective fission dynamics, often presenting with severe neurological manifestations. Current diagnostic and prognostic challenges stem from incomplete knowledge of domain-specific genotype-phenotype correlations and limited clinical data. We report a novel GTPase effector domain (GED) variant (p.Val687del) and conduct a systematic analysis of 80 reported DNM1L cases with variants in the GTPase, Middle, or GED domains. Clinical, genetic, and survival data were extracted and analyzed to evaluate associations between mutation localization and clinical outcomes. Statistical comparisons of phenotypic severity, survival, and hotspot prevalence were performed. Functional validation of the novel variant was performed through in vitro overexpression, Western blot, immunofluorescence, and transmission electron microscopy. A novel GED deletion (p.Val687del) associated with peripheral neuropathy was identified, expanding the mutational spectrum. In vitro functional studies confirmed that this variant impairs DRP1 mitochondrial localization and induces severe ultrastructural damage, including fragmentation, swelling, and vacuolation. The preserved protein expression level excludes haploinsufficiency, consistent with a dominant-negative mechanism. Within the total cohort of 81 patients (including our case), de novo variants were predominant (74.1%), with R403C representing a major mutational hotspot (28.4%). Middle domain mutations conferred the most severe prognosis, manifesting high frequencies of developmental delay (90.7%), epilepsy (83.7%), abnormal muscle tone (67.4%), abnormal EEG findings (74.4%), and cerebral atrophy (73.2%). In contrast, GTPase domain mutations primarily affected sensory pathways, with optic atrophy (57.6%) and peripheral neuropathy (27.3%) as hallmark features. Carriers of the R403C variant exhibited a 3.9-year delay in disease onset compared to non-carriers. This study establishes that mutation location in DNM1L dictates clinical severity, with Middle domain variants defining a severe encephalopathic subtype, while GTPase domain mutations predominantly target sensory pathways, leading to optic atrophy and peripheral neuropathy. These findings provide a framework for precision prognostication and targeted therapeutic strategies in DNM1L-related disorders.

To systematically review evidence of the clinical effectiveness of psychosocial interventions for adults with substance use disorder that have a co-occurring common mental health disorder or borderline personality disorder. To identify papers that estimate the cost-effectiveness of interventions for patients with substance use disorder and common mental health disorder or borderline personality disorder.

An umbrella review (a systematic review of systematic reviews) for clinical effectiveness was conducted. Systematic database searches [MEDLINE, EMBASE, PsycInfo^® (American Psychological Association, Washington, DC, USA), Cochrane Database of Systematic Reviews, and Web of Science] were carried out in February 2024. Inclusion criteria: Adults with substance use disorder and common mental health disorder or borderline personality disorder; psychosocial interventions (with or without pharmacological therapies); comparators psychosocial treatments, treatment as usual, waitlist/no treatment; systematic reviews of randomised controlled trials. Data, including critical appraisal, were extracted into a standardised form by one reviewer, and checked by another. Data were discussed in a narrative review. A literature review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and EconLit were undertaken to identify cost-effectiveness papers. An illustrative model was constructed to show how cost-effectiveness could be calculated if data were available.

Of 5420 unique records, 30 systematic reviews were included in the clinical review. The methodological quality of the reviews was generally good. Most of the interventions and many of the active comparators studied resulted in some improvement for patients. Most reviews focused on depression, anxiety or post-traumatic stress disorder; there were some looking at mixed common mental health disorder or borderline personality disorder. There was much heterogeneity both between reviews, and between the randomised controlled trials within the reviews. The results suggested integrated treatment for co-occurring diagnosis patients may be better for common mental health disorder outcomes than treatment as usual of parallel uncoordinated services. One study was identified that met the cost-effectiveness criteria. However, this reported results alongside a clinical study and was not a modelling paper. The illustrative model should aid future researchers.

Heterogeneity made it difficult to reach an overall conclusion about which therapies were best. Most reviews stated the results were not generalisable across all populations or settings. There were few reviews of borderline personality disorder; or of common mental health disorder other than anxiety/depression/post-traumatic stress disorder.

Future research comparing integrated with parallel or sequential treatment, with follow-up of 6 months or longer, and sample size large enough to encompass dropout, may be beneficial.

No implications for current practice could be recommended due to heterogeneity of reviews/randomised controlled trials within reviews.

This study is registered as PROSPERO CRD42024515813.

This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR166951) and is published in full in Health Technology Assessment; Vol. 30, No. 49. See the NIHR Funding and Awards website for further award information.

Introduction Major Depressive Disorder (MDD) is a prevalent global mental health challenge with a multifactorial etiology, including genetic, environmental, and biochemical influences. Current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), face limitations, including delayed therapeutic onset, systemic side effects, and poor permeability across the blood-brain barrier (BBB). To overcome these challenges, intranasal NE (NE) drug delivery systems have emerged as a promising approach for enhancing drug bioavailability and facilitating direct nose-to-brain transport. Methods A comprehensive review of recent advancements in NE-based drug delivery for MDD was conducted, focusing on formulation strategies, pharmacokinetic improvements, and therapeutic outcomes. Studies evaluating the efficacy of NE formulations for delivering antidepressants, antipsychotics, and natural compounds, such as curcumin and resveratrol, were analyzed. The role of mucoadhesive agents like chitosan in enhancing nasal retention and drug absorption was also explored. Results NE formulations demonstrated superior drug delivery to the CNS, bypassing the BBB and reducing systemic toxicity. Preclinical and clinical studies indicate enhanced therapeutic efficacy, increased drug concentration at target sites, and improved patient compliance. The inclusion of mucoadhesive agents further optimized nasal retention, prolonging drug absorption and enhancing therapeutic effects. Additionally, NEs mitigated hepatic first-pass metabolism, leading to lower dosing requirements and reduced side effects. Discussion Nanoemulsion-based intranasal delivery presents a promising strategy for treating MDD, offering physiological and pharmacological advantages over oral routes. By bypassing the blood-brain barrier, these systems enable rapid and targeted brain delivery, enhancing drug efficacy. The nanoscale size improves solubility and absorption of poorly water-soluble compounds like curcumin and resveratrol. Incorporation of mucoadhesive agents such as chitosan further enhances nasal retention and drug uptake. Despite encouraging preclinical results, challenges remain in translating this approach clinically. Conclusion Intranasal NE-based drug delivery presents a transformative strategy for treating MDD and other CNS disorders. By integrating nanoscale formulation approaches with tailored pharmacokinetics, this system offers improved drug efficacy, safety, and patient adherence. Future research should focus on optimizing formulations, ensuring long-term stability, and advancing clinical translation for broader CNS applications.

Mild cognitive impairment and remitted major depressive disorder increase the risk of dementia. The PACt-MD (Prevention of Alzheimer's Dementia With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) trial (NCT02386670) has shown that combined cognitive remediation (CR) and transcranial direct current stimulation (tDCS) improve cognitive outcomes by targeting executive function and presumably leveraging neurophysiological mechanisms. Our study investigated whether the magnitude of electric fields (EFs) induced by tDCS in the dorsolateral prefrontal cortex (DLPFC) predicted cognitive response in PACt-MD participants.

Data from the 143 PACt-MD participants (mean [SD] age = 71.8 [6.34] years) who received active CR+tDCS and had brain magnetic resonance imaging (MRI) were analyzed. EFs were estimated using individual MRI with tDCS electrode placement at Fz (anode) and Iz (cathode). Participants were split into high- and low-EF groups based on the median. We used linear mixed models to assess the effect of EF in the left and right DLPFC on global cognitive decline, the primary outcome of PACt-MD, over 72 months. The global cognitive decline is the average of z scores on all tests on the neuropsychological battery.

EF magnitude in the left DLPFC was associated with global cognitive decline (likelihood ratio test: p = .026). Participants with high EF showed slower cognitive decline than those with low EF, irrespective of diagnosis and APOE ε4 status. No significant association was observed for the right DLPFC.

Our findings support that high EF in the DLPFC is associated with the efficacy of CR+tDCS. In future studies, tDCS dosing that results in a higher EF in the left DLPFC may improve the cognitive outcomes of CR+tDCS.

Effective social decision-making requires understanding interpersonal dynamics involving moral content, a process supported by social cognition. When this ability is impaired, as in Mild Cognitive Impairment (MCI), individuals may struggle to act appropriately, reducing social engagement and accelerating decline.The study investigated moral decision-making and social cognition in individuals with MCI and healthy controls (N = 40; 20 per group). Participants completed tasks assessing Theory of Mind (ToM), emotion attribution, social situation understanding, and moral/conventional distinctions. Moral decisions were measured using interactive scenarios (sacrificial, real-life moral, and neutral), recording choices and response times (RTs). Additional measures included cognitive reserve, social engagement, and perceived social isolation.Results showed that individuals with MCI performed significantly worse than controls in identifying normative behaviours, with no group differences in other social cognition domains. Both groups made similar choices in moral decision-making tasks. However, individuals with MCI exhibited longer response times in morally salient scenarios, while no group differences emerged in neutral scenarios. This pattern may tentatively suggest greater processing demands in morally relevant contexts. Additionally, individuals with MCI reported lower levels of cognitive reserve and social engagement.These findings underscore the importance of assessing moral decision-making in clinical populations to support autonomy and social inclusion in ageing.

Depression is a common mental health disorder which frequently co-occurs with increased body mass index or increased waist circumference (hereafter 'overweight'), causing heightened cardiovascular risk. Unhealthy lifestyle behaviours underlie both conditions. The Multimodal Lifestyle Intervention (MLI) LEEF integrates physical activity, nutrition, and behavioural strategies, tailored to motivational challenges common in depression, offering a dual focus on mental and physical health. However, unpublished process data revealed very limited referral to MLI‑LEEF from both primary and secondary care, and consequently low initiation rates, signalling clear implementation challenges. This study addresses this gap by translating prioritised implementation determinants into conceptually and empirically grounded implementation strategies and examining what works, how, and under which conditions.

This quasi‑experimental, explanatory sequential mixed‑methods study will implement MLI‑LEEF across ten general practices and three secondary mental health care outpatient clinics in the Northern Netherlands. Implementation strategies will be developed and tailored using Causal Pathway Diagramming and applied over a six‑month period. Quantitative data will be collected before, during, and after implementation to assess proximal implementation outcomes (the immediate, observable effects of an implementation strategy), distal implementation outcomes (adoption and sustainability), service‑level penetration, and patient outcomes. Following the implementation period, semi‑structured interviews will be conducted with referrers from each participating organisation. Site‑specific topic guides, informed by each organisation's implementation plan, causal pathway diagrams, and quantitative implementation outcomes, will probe how strategies generate change (mechanisms), how they influence targeted determinants, and which contextual conditions (preconditions, moderators) shape implementation strategy functioning.

This study will respond to fieldwide calls in implementation science for rigorous, transparent, and context-sensitive approaches to developing and evaluating implementation strategies. By examining how strategies shape referral and initiation in routine general practice and specialist mental health services, and by clarifying the mechanisms and contextual conditions under which they are effective, the study will generate actionable insight into why implementation succeeds or falters in real-world care. These insights will provide essential groundwork for strengthening the reach and adoption of MLI-LEEF and will offer transferable guidance for embedding multimodal lifestyle interventions into everyday care, while advancing generalizable knowledge of how implementation strategies produce change.

10.17605/OSF.IO/XJHCB.

Compassion fatigue is a common condition among healthcare professionals continuously exposed to patient suffering, especially in high-pressure care settings such as those experienced during the COVID-19 pandemic. Evidence highlights its negative impact on mental health of staff and quality of care, as well as the need to implement effective preventive programs. Therefore, the aim of this study was to evaluate the impact of a pilot program of secondary prevention of compassion fatigue in healthcare professionals working in COVID-19 units at the Nuestra Señora de Candelaria University Hospital Complex (CHUNSC).

A quasi-experimental, longitudinal and prospective study was carried out, with pretest-posttest measures in a single group. By initial screening with the IDE-ESAPE and ProQOL-IV tools, 30 professionals with high scores of compassion fatigue or burnout were selected. The psychoeducational program, consisting of five group sessions, included mindfulness, emotional regulation and self-care. The results were evaluated at six months.

Significant reductions in compassion fatigue (p < 0.01; r = 0.48) and burnout (p < 0.01; r = 0.53) were observed, as well as an increase in compassion satisfaction (p < 0.01; r = 0.46). A total of 100% of the participants completed the intervention. Improvements were maintained at six-month follow-up.

The program was associated with significant reductions in compassion fatigue and burnout, together with an increase in compassion satisfaction. This suggests its feasibility and potential usefulness for integration into institutional strategies aimed at supporting professional well-being.