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A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20&#xa0;mg/day over 6&#xa0;weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n&#xa0;=&#xa0;31; placebo, n&#xa0;=&#xa0;32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P&#xa0;<&#xa0;0.001), but improvement was greater with memantine for global cognition at week 6 (MD&#xa0;=&#xa0;9.32; 95% CI, 4.84-13.81; P&#xa0;<&#xa0;0.001) and week 18 (MD&#xa0;=&#xa0;12.69; 95% CI, 8.67-16.71; P&#xa0;<&#xa0;0.001). FAB total scores favored memantine at week 18 (MD&#xa0;=&#xa0;2.68; 95% CI, 1.76-3.61; P&#xa0;<&#xa0;0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n&#xa0;=&#xa0;615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3&#xa0;months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k&#xa0;=&#xa0;4). The average follow-up length was 4&#xa0;months (range: 3-6&#xa0;months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6&#xa0;months, whereas only one CR RCT found consistent functional effects at 3&#xa0;months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Short-term psychodynamic psychotherapy for functional neurological disorder: A pilot randomized controlled trial.

BACKGROUND: Evidence-based psychotherapeutic treatments for Functional Neurological Disorder (FND) remain limited. This pilot trial evaluated the preliminary efficacy of Short-term Psychodynamic Psychotherapy (STPP) plus Standard Medical Care (SMC) compared with SMC alone in reducing FND symptom frequency. METHODS: Adults with FND were randomized (1:1) to receive either SMC alone or 12 weekly sessions of STPP plus SMC. The primary outcome was symptom frequency (days with symptoms in the last 4 weeks) assessed at the end of treatment (3 months) and at 6-month follow-up. Secondary outcomes included treatment response (&#x2265;50% reduction in symptom frequency) and scores on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: Of 91 randomized patients (mean age 38.2 years, 75.8% female), 81.3% completed follow-up. Intention-to-treat analysis using Linear Mixed Models showed that STPP plus SMC significantly reduced symptom frequency compared with SMC alone (estimated mean difference -5.72 [95% CI -8.68 to -2.77]; Cohen's d = 0.77; p&#x202f;<&#x202f;0.001).Treatment response was achieved by 65.8% in the intervention group versus 16.7% in controls (OR 8.21 [95% CI 2.79-24.19]; p&#x202f;<&#x202f;0.001; NNT 2.0).Significant improvements were also observed for depression (HAM-D: estimated mean difference -10.80; d = 1.45), anxiety (HAM-A: -7.94; d = 1.06), and disability (WHODAS 2.0: -5.77; d = 0.74), all p&#x202f;<&#x202f;0.001. CONCLUSIONS: STPP was associated with clinically meaningful improvements in FND symptom frequency and all secondary outcomes, with large effect sizes and high treatment response rates. These findings support the preliminary efficacy of STPP for FND and justify larger, multicenter confirmatory trials.

Humans

Acupuncture improves depressive symptoms and prefrontal cortical function in mild to moderate depressive disorder: A randomized sham-controlled trial and fNIRS study.

BACKGROUND: Depressive disorder is a common mental illness associated with substantial functional impairment. Although pharmacotherapy is widely used, its effectiveness is often limited by adverse effects and poor adherence. Acupuncture has been increasingly applied as a complementary treatment for depression, and its neurobiological characteristics remain unclear. OBJECTIVE: This randomized, sham-controlled trial aimed to evaluate the clinical efficacy of acupuncture for mild to moderate depressive disorder and to investigate its effects on prefrontal cortical function using functional near-infrared spectroscopy (fNIRS). METHODS: Patients with mild to moderate depressive disorder were randomly assigned to a real acupuncture (RA) group or a sham acupuncture (SA) group and received standardized treatment for 8 weeks. Clinical outcomes were assessed using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Short Form-36 Health Survey (SF-36), and a traditional Chinese medicine syndrome score. A subset of participants underwent fNIRS assessment during resting-state and task-based conditions to evaluate prefrontal cortical activation and functional connectivity. RESULTS: Compared with baseline, the RA group showed significant reductions in SDS and SAS scores and significant improvements in SF-36 emotional domains, with effects emerging at Week 4 and persisting up to 12 weeks after treatment. Improvements were greater and more stable in the RA group than in the SA group. fNIRS analyses revealed enhanced activation in dorsolateral and medial prefrontal regions and strengthened prefrontal functional connectivity following acupuncture, whereas neural changes in the SA group were limited. CONCLUSION: Acupuncture is effective for improving depressive and anxiety symptoms and quality of life in patients with mild to moderate depressive disorder. Modulation of prefrontal cortical activation and connectivity may underlie its antidepressant effects.

Humans

Investigating telomere length and hTERT-MNS16A VNTR polymorphism in Bipolar disorder: Insights into clinical features.

OBJECTIVE: To compare leukocyte telomere length (LTL; T/S ratio) and hTERT-MNS16A VNTR polymorphism between patients with bipolar disorder (BD) and healthy controls, and to examine their associations with clinical features in BD. METHODS: A total of 179 participants (100 BD patients, 79 healthy controls) were enrolled. Relative LTL was assessed by qPCR-based T/S ratio; hTERT-MNS16A VNTR genotyping by PCR and gel electrophoresis. Clinical variables including episode frequency, illness duration, age at onset, symptom severity scales, first episode polarity, and family history of mood disorder were evaluated. RESULTS: No significant differences were observed between BD patients and healthy controls in T/S ratio or hTERT-MNS16A VNTR genotype distributions (all p > 0.05). Within the BD group, S allele carriers (L/S or S/S) had significantly more depressive episodes than L/L homozygotes (1.45 &#xb1; 2.58 vs. 0.61 &#xb1; 1.52; p = .040). Significant inverse correlations were identified between T/S ratio and depressive episode count (&#x3c1; = -0.220, p = .028) and total mood episodes (&#x3c1; = -0.207, p = .039). Multivariable negative binomial regression revealed four independent predictors of depressive episode frequency: lower T/S ratio (p = 0.005), S allele carriage (L/S or S/S genotypes) (p = 0.001), first depressive episode polarity (p < 0.001), and family history of mood disorder (p = 0.035). CONCLUSION: Although LTL and hTERT-MNS16A VNTR genotype did not differ between BD patients and healthy controls, shorter telomere length and S allele carriage were independently associated with higher depressive episode frequency within the BD group, implicating telomere biology and hTERT genetic variation in the biological substrate of depressive illness burden.

Humans

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

Applications of quantum AI in brain disorder diagnosis: A systematic review.

BACKGROUND AND OBJECTIVE: Brain disorder diagnosis and prediction remain challenging because neuroimaging, electrophysiological, behavioral, and multimodal data are high-dimensional, noisy, heterogeneous, and limited by small clinical cohorts. This systematic review synthesised applications of quantum artificial intelligence (QAI) for brain disorder diagnosis, prediction, detection, and monitoring. METHODS: Following PRISMA guidelines, studies published from 2016 to 13 January 2026 were retrieved from Scopus, Web of Science, and IEEE Xplore. After screening, 36 studies met the eligibility criteria and were qualitatively analysed according to disorder category, data modality, QAI method, implementation setting, validation strategy, and performance. RESULTS: At the broader disease-group level, neurodegenerative disorders were the most frequently investigated, followed by mental health and psychiatric disorders. At the individual level, Parkinson's disease and schizophrenia were the leading applications, followed by depression, anxiety, Alzheimer's disease, and stress-related tasks. MRI-based modalities were the most frequently used data source, followed by multimodal data and EEG. Methodologically, primary QAI approaches were dominated by quantum neural and QDL architectures, followed by quantum-inspired optimization or feature-selection methods and quantum-kernel/conventional QML classifiers. Qiskit/IBM Quantum and PennyLane were the most frequently reported quantum software frameworks. However, most studies relied on simulators, classical quantum-inspired implementations, or unclear implementation settings, with limited real-hardware evaluation. CONCLUSIONS: QAI shows emerging potential for brain disorder analysis, particularly through hybrid quantum-classical learning, quantum neural architectures, quantum-kernel methods, and quantum-inspired optimization. Nevertheless, current evidence remains preliminary and requires larger datasets, subject-level and external validation, fair classical benchmarking, noise-resilient circuits, real quantum hardware evaluation, explainability, and clinical validation.

Humans

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4&#x207a; regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogot&#xe1;, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (&#x223c;2.4-fold decrease in median expression; p&#x202f;=&#x202f;0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p&#x202f;=&#x202f;0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p&#x202f;=&#x202f;0.035) and Amerindian ancestry (p&#x202f;=&#x202f;0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans

Linking women leaving jail to medications for opioid use disorder: Costs to implement pre-release telehealth and peer navigation services.

AIMS: Telehealth and peer navigation are feasible strategies for connecting women in the criminal-legal system with medications for opioid use disorder (MOUD), yet implementation costs are not well understood. This study conducted a microcosting analysis of two interventions for women leaving jail in Kentucky: pre-release, PreTreatment Telehealth with a MOUD provider (TH-Only) and PreTreatment Telehealth combined with peer navigation (TH+PN) through the Justice Community Opioid Innovation Network (JCOIN). METHODS: From the provider perspective, we estimated total start-up costs, total intervention costs, and average cost per participant. Women participating in the clinical trial were randomly assigned to TH-Only (n=299) or TH+PN (n=301). Start-up costs were incurred primarily in 2019 - 2020; intervention costs represent expenses in 2021 - 2023. Cost data were collected from study and agency financial records and interviews with research staff and analyzed using Microsoft Excel (version 16.90.2). RESULTS: Start-up costs were $36,320, comprising planning, meetings, travel, and supplies. The total cost of TH-Only was $60,767, representing 259 telehealth sessions with an average duration of 47 minutes. Total cost of TH+PN was $472,148 based on 270 telehealth sessions (48 minutes), 268 peer navigation (PN) sessions (30 minutes), and 12 weeks of PN support post-release per participant. Average cost per TH-Only participant was $235 and per TH+PN participant was $1,760. CONCLUSIONS: Telehealth may be a relatively low-cost approach for jails lacking on-site MOUD services. Although more costly, combining telehealth with PN may add value by supporting service continuity and facilitating linkage to treatment during the jail to community transition.

Humans

Symptoms of Anxiety in Adults with ADHD: A Systematic Review and Meta-Analysis of Case-Control Studies.

OBJECTIVE: Research suggests there is a higher prevalence of anxiety in individuals with ADHD compared to those without ADHD. However, estimated prevalence rates vary greatly due to differences in methodologies used across studies. This study is the first meta-analysis investigating differences in anxiety measure scores between adults with and without ADHD, and possible moderators of this effect. METHOD: Our analysis included 58 studies that compared anxiety scores in adults with/without ADHD (N = 18,821; k = 112). RESULTS: The average effect size (Hedges's g) of anxiety scores in those with ADHD relative to controls was 0.77 (SE = 0.066); a medium effect. The only significant moderator was the type of comparison group used, with comparisons to non-clinical control groups (g = 0.954, SE = 0.08) yielding significantly larger effects than comparisons to clinical control groups (g = 0.437, SE = 0.09). None of the other moderator variables examined (Method of characterising ADHD, Anxiety Measure Type, Anxiety Measure Focus, Age or Gender) moderated the effect. There was some evidence of publication bias, therefore results should be interpreted with this in mind. CONCLUSION: Overall, this study indicates that ADHD is associated with higher levels of anxiety symptomology. This has important implications in the diagnosis and treatment of individuals presenting with ADHD or anxiety, including the consideration and screening of each of these conditions as potentially co-occurring with the other. Adaptions made to clinical practice in line with this would better support this population, improve symptom management and overall quality of life. Suggestions for future research are discussed.

Humans

Integrated proteomic and acetylomic analyses reveal the metabolic reprogramming associated with increased tylosin-equivalent concentration in Streptomyces xinghaiensis sf106-B1.

Deciphering the metabolic basis of high-yield antibiotic production in Streptomyces is crucial for strain optimization. Atmospheric and room-temperature plasma (ARTP) mutagenesis of Streptomyces xinghaiensis sf106 generated a mutant with a 30% increase in tylosin-equivalent concentration (&#x3bc;g/mL). 4D-FastDIA quantitative proteomics identified 279 differentially abundant proteins enriched in the Type I polyketide synthase (PKS) pathway, with increased abundance of key macrolide-biosynthesis-related proteins. Lysine-acetylome profiling identified 1152 differentially abundant acetylation sites and revealed altered acetylation of enzymes involved in fatty acid metabolism and the tricarboxylic acid (TCA) cycle, suggesting adjustments in central metabolism associated with acyl-CoA precursor availability and energy generation. Integration of proteomic and acetylomic data suggests coordinated changes in protein abundance and lysine acetylation associated with the increased tylosin-equivalent concentration. These results highlight candidate nodes for rational metabolic engineering of S. xinghaiensis.

Streptomyces