BackgroundSocial anxiety disorder (SAD) is characterized by a significant and persistent fear of social or performance situations. The prevalence of SAD has gradually increased recently, and the unique advantages of digital interventions (DIs) have gained traction in psychiatric disorders. However, there is currently no comprehensive review comparing the effectiveness of diverse DIs for SAD.MethodsRandomized controlled trials (RCTs) evaluating DIs for patients with SAD were identified by searching the PubMed, Cochrane Library, and Embase databases from January 1, 1995, to March 31, 2025. The study protocol for this network meta-analysis was registered in PROSPERO. Data were analyzed via Bayesian framework network meta-analysis.ResultsForty-two RCTs were included. The results showed that DIs exerted better efficacy than non-digital interventions and wait-list controls (WLC). Different forms of internet-based cognitive behavioral therapy (ICBT) demonstrated robust effects across all four outcomes. Internet-based cognitive therapy (ICT) yielded favorable effects in reducing social anxiety and depressive symptoms. VR showed relatively large effect sizes for improving quality of life.ConclusionDIs can be recommended as adjunctive or combined treatments for SAD. Different forms of ICBT show consistent efficacy and can serve as the first-line option among digital interventions. We recommend promoting the application of DIs to expand treatment coverage for SAD and overcome the limitations of traditional psychotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251077835.
The ECHO study: compassion-focused therapy for young voice hearers and their caregivers. A pilot study
BackgroundVoice hearing can occur in healthy people without a trigger, be caused by a traumatic event, or occur as part of a psychiatric disorder. There are still many gaps in our understanding of voice hearing, and research in this field can be challenging, maybe because it is associated with shame and stigma. Those who experience distress by voice hearing could benefit from a treatment, aimed directly at that. The ECHO manualized treatment is based on the principles of compassion-focused therapy (CFT).MethodsTreatment will take place on several different psychiatric hospitals in the Region of Southern Denmark. Treatment consists of a 10-session, manualized CFT for voice hearing. Caregivers participate in half of the sessions, and a recording of the voice content is made, which the caregivers are encouraged to listen to. The study is designed as a prospective single-arm pre–post intervention study using a mirror-image approach, in which participants serve as their own controls over time. The intervention group consists of (N = 60) voice-hearing adolescents aged 13–18 years. Additionally, a clinical comparison group (who also receive the intervention) of (N = 20) individuals aged 18–20 years with first-episode schizophrenia and voice hearing is included for descriptive and exploratory analyses. Data are collected 3 months prior to CFT treatment, immediately before the start of treatment, immediately after treatment is completed, and at 1 month follow-up. Data will be centered around social cognition, perceived social safeness, social connectedness, general well being, auditory hallucinations and compassion.DiscussionThe ECHO study addresses the wellbeing and thriving of an overlooked group of young people. The results of this study will provide information about who the voice hearers are, what challenges they face, and how they perceive them. The results will also provide information about the feasibility and efficacy of the treatment manual and, thus, its potential further implementability. Caregivers participate in half of the sessions, to facilitate a common language about mental states and voice hearing. To support their understanding, a recording of the voice content is made and the caregivers are encouraged to listen to it. We suggest that when caregivers understand the young voice hearers’ experiences, they can adjust their expectations and approach accordingly. We also suggest that by sharing the voice content, the young voice hearer will feel less isolated.Study protocol registrationhttps://clinicaltrials.gov/study/NCT07314515, identifier NCT07314515.
New York boys club has a time-tested recipe to protect members’ mental health
NEW YORK — A couple of years ago, a reporter approached the Boys’ Club of New York looking to interview some of its middle-schoolers for a story about the mental health crisis in boys.
It’s easy to see why. Many of the about 2,500 boys who participate in the 150-year-old organization’s after-school and weekend activities come from disadvantaged socioeconomic backgrounds, often living in single-parent households or facing the threat of immigration enforcement. With limited access to academic and developmental support, the risk factors are plentiful.
A novel mutation in SETD1A is associated with early-onset epilepsy—a rare case report
SET Domain Containing 1A (SETD1A) is a histone H3K4 methyltransferase implicated in neurodevelopmental disorders. Pathogenic variants in this gene are associated with schizophrenia, intellectual disability, and epilepsy. Here, whole-exome sequencing and Sanger sequencing were performed on a 4-year-old Chinese girl with early-onset epilepsy and her unaffected parents. A novel de novo heterozygous variant in SETD1A (NM_014712.3: c.1067C > T/p.Ser356Phe) was identified in a patient presenting with focal-to-bilateral tonic–clonic seizures, beginning at 3 months of age. Neuroimaging revealed a normal brain MRI, and comprehensive neuropsychological assessment indicated preserved cognitive function. The variant was absent in 200 local controls and classified as likely pathogenic per ACMG criteria. This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, highlighting the value of genetic testing in infants with unexplained epilepsy.
Local field potentials for target localization in centromedian deep brain stimulation for epilepsy
ObjectiveTo evaluate whether local field potential (LFP) spectral profiles can serve as a candidate “spectral fingerprint” for physiological confirmation of centromedian-parafascicular (CM–Pf) targeting during thalamic deep brain stimulation (DBS) for drug resistant epilepsy (DRE).MethodsThis is a retrospective study of 10 patients (20 leads) who underwent CM-DBS implantation for DRE at a single tertiary center. Postoperative CT and preoperative MRI were co-registered, normalized to the Montreal Neurological Institute (MNI) space, and reconstructed using Lead-DBS software to anatomically localize contacts. BrainSense™ Survey recordings were obtained at least 3 weeks post-implant during routine programming. LFP frequency content was analyzed, and prominent peaks were identified and classified into canonical frequency bands (theta, alpha, beta). These spectral profiles were then mapped to MRI-based anatomical localizations, and statistical tests were applied to assess associations between peak patterns, contact localizations and thalamic subregions.ResultsContacts were distributed as follows: 50 in the CM, 16 in the Parafascicular (Pf), 15 in the Centrolateral, 8 in the Mediodorsal, and 7 in the Ventrolateral (VL) nuclei. Of the 10 representative spectral localizations confined to the CM/CM-Pf region, 8 (80%) displayed a distinct dual-peak spectral profile with peaks in the theta/low alpha (5.5–9 Hz) and high beta (20–30 Hz) bands (mean frequencies: 7.63 Hz and 21.02 Hz, Fisher’s exact test, p < 0.001). Single-peak profiles showed no significant association with specific nuclei (p = 0.871). Contacts overlapping other thalamic nuclei more frequently exhibited narrow 10–15 Hz peaks (p = 0.005) or triple-peak profiles (p = 0.02), suggesting mixed structural contributions.ConclusionA dual- band candidate spectral pattern consisting of theta/low alpha and high beta peaks was associated with the CM-Pf region in this cohort. This finding provides early evidence supporting the feasibility of incorporating passive LFP recordings as a physiologic marker of target engagement. Future work to prospectively compare bipolar survey-based localization with monopolar recording strategies could enable development of a state-based, physiologically informed spectral atlas to refine CM-Pf targeting in thalamic neuromodulation for DRE.
Autistic- and attention-deficit/hyperactivity disorder-like traits: differential associations with burnout, depression and anxiety, and empathy among Japanese junior residents
IntroductionBurnout, depression, and anxiety are major concerns among physicians because they affect individual well-being, patient care, and healthcare systems. Neurodevelopmental traits, including autistic-like traits (ALTs) and attention-deficit/hyperactivity disorder (ADHD)-like traits (ADHLTs), may increase vulnerability to psychological distress. However, little is known about how these traits relate to burnout, depression and anxiety, and empathy among junior residents.MethodsIn this cross-sectional study, 148 junior residents from two teaching hospitals in Japan completed validated measures of ALTs (21-item Japanese version of the Autism-Spectrum Quotient), ADHLTs (Adult ADHD Self-Report Scale Screener), burnout (Maslach Burnout Inventory), depression and anxiety (Hospital Anxiety and Depression Scale), physician–patient empathy (Jefferson Scale of Physician Empathy), and psychological flexibility and inflexibility processes (Valuing Questionnaire, Cognitive Fusion Questionnaire-7, and Work-related Acceptance and Action Questionnaire). Associations were examined using multivariable logistic and linear regression analyses. Exploratory statistical mediation analyses using structural equation modeling examined indirect associations through psychological flexibility and inflexibility processes.ResultsThe prevalence of ALTs and ADHLTs was 23.6% for each trait. ALTs were associated with lower personal accomplishment, a burnout dimension; higher depression and anxiety; and lower physician–patient empathy. ADHLTs were associated with greater emotional exhaustion, another burnout dimension. In exploratory statistical mediation analyses, progress toward values, a core process of psychological flexibility, showed a significant indirect association between ALTs and personal accomplishment, and the direct association was attenuated and no longer statistically significant after including the process variables. Significant indirect associations through progress toward values were also observed for the associations of ALT with depression and anxiety and empathy. Cognitive fusion, a core process of psychological inflexibility, showed a significant indirect association between ADHLTs and emotional exhaustion. Overall, neurodevelopmental traits were associated with distinct patterns of psychological functioning, suggesting variability in both vulnerability and adaptive processes.DiscussionNeurodevelopmental traits such as ALTs and ADHLTs were significantly associated with burnout dimensions, depression and anxiety, and physician–patient empathy among junior residents. Psychological flexibility and inflexibility processes, particularly progress toward values and cognitive fusion, may be relevant to these associations. Process-based support strategies may warrant further investigation for residents with elevated neurodevelopmental traits.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R00005, identifier UMIN000046897.
Autism service barriers for Latine children and their families: a participatory approach to adapting autism diagnostic care
IntroductionLatine children from families with limited English proficiency (LEP) experience barriers to timely autism diagnosis resulting in persistent health inequities. This participatory mixed-methods study examined these barriers and identified multi-level strategies to adapt diagnostic care models for Spanish-speaking Latine families.MethodsParticipants included twelve caregivers of thirteen autistic children with parent reported diagnosis of autism, twelve clinicians, and six care coordinators. All participants completed surveys and participated in qualitative interviews or focus groups.ResultsQuantitative findings revealed significant lag between caregiver’s first developmental concern and diagnosis, limited autism knowledge, and difficulty navigating care. Qualitative results highlighted systemic barriers, including clinician-patient language discordance, interpreter inaccuracies and quality variability, cultural stigma, and long waitlists. Clinicians reported challenges with communicating about autism with Spanish-speaking families and emphasized language and cultural differences as primary barriers. Caregivers described social isolation, mistrust of health systems, and emotional distress compounded by immigration-related stressors.DiscussionFindings underscore the need for structural adaptation of care approaches beyond translation services.
Loneliness, rumination, and adolescent psychological crisis in China: a pilot moderated mediation study
BackgroundAdolescent psychological crisis—encompassing depressive disorder, anxiety disorder, and suicidal ideation—is a major public health challenge. One in five adolescents experiences a clinically significant mental health condition globally. Loneliness is a well-documented, modifiable risk factor for these outcomes. However, the exact cognitive-emotional pathways linking loneliness to acute psychological crisis remain unclear. This is particularly true in China, where rapid social change and intense academic pressure increasingly strain adolescent mental health. We do not yet fully understand how protective resources might buffer these specific pathways.Objectives and methodsThis pilot study tests a moderated mediation model based on the Evolutionary Theory of Loneliness and the stress-vulnerability framework. We investigate ruminative thinking as a cognitive-emotional mediator between loneliness and psychological crisis. We also test whether perceived social support and psychological resilience moderate distinct stages of this pathway. Based on a pilot sample of N = 312 Chinese adolescents (ages 12–18), we use structural equation modelling (SEM), confirmatory factor analysis (CFA), and Hayes’ PROCESS Macro (Model 14) with 5, 000 bootstrap replications. Two-wave longitudinal data (n = 187, 8-week interval) were available for the depression outcome only; the anxiety and suicidal-ideation pathways were examined cross-sectionally.ResultsLoneliness is significantly associated with depressive symptoms (β = 0.43, p < 0.001), anxiety (β = 0.38, p < 0.001), and suicidal ideation (β = 0.27, p < 0.001). Ruminative thinking accounts for 40–46% of the total indirect association across all three outcomes. Social support buffers the transmission from loneliness to rumination (b = −0.16, p = 0.002, ΔR2 = 0.023), while resilience buffers the transmission from rumination to crisis (b = −0.19, p < 0.001, ΔR2 = 0.031).ConclusionsThese preliminary, exploratory findings are consistent with the possibility that ruminative thinking partially accounts for the cross-sectional association between loneliness and adolescent psychological crisis in China, and with social support and resilience attenuating this association at potentially distinct stages. Because the pilot is underpowered for the moderated mediation model and the available longitudinal evidence covers depression only, the moderation and stage-specificity results should be read as hypothesis-generating rather than confirmatory. A planned full-scale study (N ≥ 1, 200) will test these mechanisms further. We also outline initial practical implications for school-based interventions.
Treating addiction with an addictive drug: the ketamine paradox revisited
BackgroundSubstance use disorders (SUDs) and treatment-resistant depression (TRD) remain a major global health challenge, marked by high relapse rates and limited long-term effectiveness of existing treatments. Ketamine, a glutamatergic modulator with rapid neuroplastic effects, has emerged as a novel intervention for TRD and is increasingly investigated as an adjunctive treatment for addiction, yet concerns about its abuse liability persist.ObjectiveThis review critically evaluates ketamine’s therapeutic potential for SUDs while examining its neurobiological mechanisms, clinical efficacy, and risk of misuse within a unified risk–benefit framework.MethodsA structured narrative review conducted in accordance with the SANRA framework using the PubMed, Scopus, PsycINFO, and Web of Science databases, covering literature published until March 2026. Eligible studies included clinical trials, experimental studies, and mechanistic investigations relevant to ketamine use in addiction and depression. Evidence was synthesized thematically across the domains of efficacy, mechanisms, and safety.ResultsAcross alcohol and cocaine use disorders, ketamine combined with psychotherapy has demonstrated promising reductions in craving and increases in abstinent days in small-to moderate-sized Phase 2 trials. However, findings remain difficult to generalize due to considerable variability in dosing strategies, comparator conditions, and follow-up periods. Effects on relapse prevention have been more inconsistent and less reliably positive. Mechanistically, ketamine promotes synaptic plasticity via NMDA receptor antagonism and downstream glutamatergic signaling, potentially disrupting maladaptive reward-related memories and reversing maladaptive neurocircuitry involved in both depression and addiction. While acute adverse effects are generally transient under clinical supervision, ketamine carries a well-established risk of misuse, particularly in unsupervised or high-dose settings.ConclusionsKetamine represents a promising but still experimental intervention for both refractory depression and selected SUDs. Its clinical use depends on careful patient selection, structured delivery, and integration with psychotherapy. Although ketamine may redefine treatment paradigms for TRD and addiction, larger-scale trials and long-term safety data are essential to define its role within psychiatric and addiction treatment frameworks.
Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study
IntroductionIntravenous (IV) ketamine and intranasal esketamine are NMDA receptor antagonists used for treatment-resistant depression (TRD). Both have demonstrated efficacy in controlled trials, but observational evidence from real-world community settings is limited.MethodsWe conducted a single-center retrospective cohort study of adults aged 18 to 65 receiving induction therapy for TRD with intranasal esketamine or IV ketamine at a community psychiatric clinic from January 1 through December 31, 2025. Patients with prior exposure to either medication or to oral ketamine derivatives were excluded. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to end of induction. Secondary outcomes included response (≥50% PHQ-9 reduction), remission (final PHQ-9 ≤4), clinically meaningful improvement (≥5 PHQ-9 reduction), induction completion, and adverse events. Within-group and per-protocol analyses were exploratory.ResultsSixty-three patients met inclusion criteria (esketamine n=37; IV ketamine n=26). Baseline PHQ-9 scores were similar (18.22±4.49 vs. 18.27±5.41; P = 0.967), as was mean change from baseline (-10.31±5.59 vs. -9.50±5.69; mean difference 0.81, 95% CI -2.12 to 3.75; P = 0.589). Response rates were 64.9% vs. 69.2% (RR 0.94, 95% CI 0.66 to 1.33; P = 0.790), remission 32.4% vs. 23.1% (RR 1.41, 95% CI 0.61 to 3.26; P = 0.573), and clinically meaningful improvement 83.8% vs 73.1% (RR 1.15, 95% CI 0.87 to 1.51; P = 0.353). Induction completion exceeded 90% in both groups; one patient per cohort discontinued from intolerable side effects, and no serious adverse events occurred. Within-group PHQ-9 reduction was large: 10.31±5.59 points (paired t[34]=10.91; P<0.001; Cohen’s d=1.84) for esketamine and 9.50±5.69 points (paired t[23]=8.18; P<0.001; Cohen’s d=1.67) for ketamine. Findings remained statistically significant and clinically large under a pre-specified baseline observation carried forward (BOCF) sensitivity analysis (Cohen’s d=1.65 and 1.45).ConclusionsInduction therapy with intranasal esketamine and intravenous ketamine was associated with robust antidepressant effects in a community outpatient setting, consistent with prior trial data. The modest sample size limits power to detect between-group differences and increases the risk of type II error; the absence of statistically significant between-group differences should therefore not be interpreted as evidence of equivalence. Protocol asymmetry between arms (esketamine: 12 sessions over 8 weeks; IV ketamine: 6 sessions over 3 weeks) further limits direct comparison of endpoint values between groups. Practical considerations including insurance coverage, cost, and administration logistics may help guide treatment selection. Longitudinal follow-up is planned to characterize treatment durability.