Synaptic development and functionality have been considered as fundamental mechanisms underlying a range of neuropsychiatric disorders, including schizophrenia. Emerging evidence from biological and clinical studies implicates mutations in the Disrupted-in-Schizophrenia-1 (DISC1) gene in the pathogenesis of schizophrenia. In this study, genetic interactions among a select set of risk factor genes are examined using the unique model system: neuromuscular junctions (NMJs) in Drosophila. We found that dnlg1, the Drosophila homolog of the human Neuroligin-1, which encodes the NLGN1 protein, genetically interacts with DISC1 in synaptic development. We show that DISC1 overexpression in the dnlg1null heterozygous background causes synaptic alterations at the NMJs that are distinct from those in the wild-type background. Loss of dnlg1 enhanced the DISC1 overexpression phenotype in synaptic formation, strongly suppressing the formation of synaptic boutons. These results thus suggest an intriguing converging mechanism regulated by DISC1 and Neuroligin in the developing glutamatergic synapses.
Plant-derived bioactives, the gut–brain axis, and neurodegenerative diseases: mechanistic roles of diet–microbiota interactions
Diet is increasingly recognized as a potential upstream modulator of the gut-brain axis (GBA) through its effects on the microbiome, microbial metabolites, and host immune and endocrine responses. The GBA is a complex, bidirectional network connecting the gastrointestinal tract and central nervous system, with diet influencing microbial community structure and metabolic output. Plant-based diets, such as Mediterranean and MIND, have been associated with increased production of anti-inflammatory microbial metabolites and improved barrier function, while high calorie/low nutrient diets are often linked to increased immune activation and barrier dysfunction. However, while microbial metabolites, especially short-chain fatty acids, indoles, bile acids, and isothiocyanates, have been proposed as mediators of neuroprotective effects, their role in neurodegenerative diseases remains an area of active investigation, with evidence largely derived from preclinical and associative human studies. Cruciferous vegetables, especially broccoli sprouts, are an emerging focus of research for their bioactive compound sulforaphane, which activates Nrf2-centered cytoprotective pathways. Animal and early human studies suggest sulforaphane can improve cognitive and behavioral outcomes, though larger clinical trials are needed. Personalized, microbiota-targeted dietary interventions may offer scalable strategies for managing neuroinflammatory and neurodegenerative conditions, and we emphasize the need for integrated research across diet, microbiome, and brain health.
Perceived stress and depression among Chinese nurses: a cross-sectional mediation analysis of psychological flexibility and its components
BackgroundPerceived stress is a significant risk factor for depression among healthcare professionals. While this fundamental relationship is well-documented, the potential mediating mechanisms—specifically the role of psychological flexibility and its distinct components—in buffering the impact of perceived stress on depression within the nursing community remain poorly understood.MethodsThis cross-sectional study recruited 3,920 nurses from three tertiary Grade A public hospitals in Xi’an, China, using convenience sampling, of whom 3,611 were included in the final analysis. Data were collected online using the Chinese versions of Cohen’s Perceived Stress Scale and the Comprehensive Assessment of Acceptance and Commitment Therapy Processes, as well as the Patient Health Questionnaire-9. Pearson correlation analyzes and mediation analysis were conducted to examine the associations among perceived stress, psychological flexibility, and depression.ResultsDepression was positively correlated with perceived stress (r = 0.63, p < 0.01). Mediation analysis indicated that perceived stress was significantly associated with depression both directly (b = 0.47, 95% CI: 0.45 to 0.49) and indirectly via psychological flexibility (b = 0.12, 95% CI: 0.11 to 0.13) and its components, including acceptance and cognitive defusion (b = 0.14, 95% CI: 0.13 to 0.15), and values and committed action (b = 0.06, 95% CI: 0.04 to 0.08). The indirect association through mindfulness and self-as-context was not significant (b = 0.01, 95% CI: 0.00 to 0.02).ConclusionsPsychological flexibility and some of its components were involved in partial indirect associations between perceived stress and depression among Chinese nurses. These findings suggest that psychological flexibility may help understand how perceived stress is statistically associated with depression in this population. Given the cross-sectional design, however, the results should be interpreted as statistical associations rather than evidence of causal relationships.
Beyond empirically supported treatments: a new contextualized evidence framework for evidence based psychology
Over the past three decades, criteria for Empirically Supported Treatments (ESTs) have strengthened methodological rigor in psychotherapy research by prioritizing randomized controlled trials and systematic evidence synthesis. However, prevailing frameworks remain largely centered on efficacy under controlled conditions, offering limited operational guidance for integrating contextual factors that critically shape real-world effectiveness. We propose the Contextualized Empirically Supported Treatment Framework (C-EST), a normative and operational model that integrates certainty of evidence with structured appraisal of contextual domains essential for clinical decision-making, guideline development, and policy. Building on the Tolin criteria, GRADE, GRADE-CERQual, and the GRADE Evidence-to-Decision approach, C-EST embeds assessment of empirical certainty within five interconnected domains (1): empirical evidence (2), critical appraisal of the body of evidence, (3) functional and cultural impact, (4) contextual factors, including values, acceptability, feasibility, and equity, and (5) transparency and living evidence. Rather than relying on binary classifications (“supported” vs. “unsupported”), the framework enables nuanced judgments such as “supported with contextual concerns,” explicitly documenting boundaries of applicability. Using Cognitive Behavioral Therapy for depression and psychological interventions for postpartum depression as illustrative cases, we demonstrate how contextual appraisal refines, rather than weakens, established evidence classifications. By aligning internal validity with external, cultural, and equity relevance, C-EST transforms evidence evaluation from a static designation into a dynamic decision-support tool. Integrating contextual evidence is not an ethical add-on but a methodological imperative to ensure that psychological treatments are not only efficacious, but applicable, equitable, and responsive to diverse real-world mental health needs.
Non-invasive electrical stimulation for sleep disturbances in adults: protocol for an evidence−mapping umbrella review of systematic reviews and meta−analyses with subgroup analysis by intervention type and population
BackgroundSleep disturbances affect 10%–30% of adults worldwide. Non−invasive electrical stimulation (e.g., transcranial electrical stimulation) has emerged as a promising non−pharmacological intervention. Although numerous systematic reviews and meta−analyses have been published, they vary considerably in methodological quality, populations, intervention types, and conclusions. No umbrella review has yet synthesised the evidence across different modalities and populations. This evidence mapping umbrella review aims to systematically chart the existing systematic reviews, assess methodological quality, quantify overlap, and describe evidence patterns across diverse modalities and populations.MethodsFollowing JBI guidelines, we will search PubMed, Embase, Cochrane Database of Systematic Reviews, Web of Science, PsycINFO, and Scopus (inception to April 2026), restricted to English. Grey literature will be searched via PROSPERO, ClinicalTrials.gov, Google Scholar (first 200 records), and reference list screening (snowballing). We will include systematic reviews and meta−analyses of randomised controlled trials evaluating any non−invasive electrical stimulation for sleep outcomes. Two reviewers will independently screen, extract data, and assess methodological quality using AMSTAR 2. Primary study overlap will be quantified by the Corrected Covered Area. Where feasible, we will calculate 95% prediction intervals, perform Egger’s regression tests, and conduct excess significance tests using review-level summary estimates. Subgroup analyses will be stratified by intervention and population type. Sensitivity analyses will exclude: (1) reviews with critically low AMSTAR 2 ratings, (2) preprints, (3) reviews at high risk of reporting bias, and (4) studies where sleep is not the primary outcome. The primary outcome is subjective sleep quality; total sleep time is a key secondary outcome. Evidence will be graded using the Fusar−Poli classification, with GRADE for key outcomes.DiscussionThis umbrella review will provide the highest level of evidence synthesis, identifying modalities with more consistent or higher certainty evidence and highlighting areas where evidence remains uncertain. Limitations include restriction to English (which may disproportionately impact modalities such as TEAS), expected heterogeneity, and possible insufficient data for some subgroup analyses. All amendments have been documented in PROSPERO (CRD420261357590).Clinical Trial Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261357590.
A bidirectional relationship between atrial fibrillation and depression: epidemiology, mechanisms, and clinical implications
Atrial fibrillation (AF) represents a common cardiac arrhythmia that carries substantial morbidity and mortality risks, whereas depression serves as a significant psychological factor affecting cardiovascular health. Recent findings underscore a reciprocal relationship between AF and depression, suggesting that depression may heighten the likelihood of developing AF, while AF may, in turn, worsen depressive symptoms. This review aims to provide a thorough examination of the epidemiological features that underpin this relationship, focusing on population-based research that clarifies prevalence rates and associated risk factors. Furthermore, it delves into the intricate biological and psychosocial mechanisms that connect these two conditions, which include dysregulation of the autonomic nervous system, inflammation, neurohormonal pathways, and behavioral influences. The clinical ramifications of this reciprocal association are also addressed, highlighting the necessity for integrated screening and management approaches to enhance patient outcomes. By consolidating existing research, this article seeks to enrich the understanding of the relationship between AF and depression, as well as to assist clinicians in optimizing therapeutic strategies tailored to address this dual burden.
Plasma microRNA signatures in drug-naïve Romanian adolescents with first-episode psychosis
Psychotic disorders are a group of severe psychiatric conditions with onset typically occurring in adolescence or early adulthood. Despite significant efforts to identify clinically useful candidates, no validated biomarkers for psychiatric disorders currently exist. The diagnosis of psychotic disorders is exclusively based on clinical assessment, significantly affected by individual differences and symptom overlap. Although circulating microRNAs (miRNAs) have emerged as potential peripheral biomarkers for early diagnosis and disease evolution, most studies concentrate on adult, medicated cohorts. Studies on miRNA profiles in drug-naïve adolescents with first-episode psychosis (FEP) are scarce. This study aims to identify the plasma miRNA profile in treatment-naïve Romanian adolescents with first-episode psychosis and to compare it with that of age- and sex-matched healthy controls. The plasma from 14 adolescents, seven drug-naïve FEP and seven and age-matched controls (CTRL) aged 15–18 years was collected. Psychiatric symptoms were assessed using PANSS, HAM-D, and YMRS scales. The levels of 179 miRNAs were assessed using qRT-PCR. A case-control analysis on miRNAs levels between FEP and CTRL was performed, as well as correlations with clinical measures. Twenty-one miRNAs showed significantly lower levels and two higher levels in FEP patients compared to controls. After adjustment for multiple comparisons, miR-125a-5p, miR-205-5p, miR-145-5p, miR-363-3p, and miR-23b-3p remained statistically significant (FDR<0.05). Notably, miR-125a-5p, miR-23b-3p, and miR-146a-5p levels negatively correlated with psychotic, depressive, and manic symptom severity, while miR-16-5p and miR-363-3p positively correlated with symptom scores. Comparison with previous studies indicated limited overlap, reflecting potential influences of age, treatment status, and genetic or environmental factors. This work demonstrates that Romanian treatment-naïve adolescents with first-episode psychosis had a unique circulating miRNA profile correlated with symptom severity, indicating their potential as early-stage biomarkers. The results underscore the necessity of accounting for age, treatment status, and environmental variables in the interpretation of miRNA modifications in psychotic illnesses.
Genetic–exposome interactions and aging clocks in dementia: the ReDLat2 initiative
Nature Medicine, Published online: 28 May 2026; doi:10.1038/s41591-026-04433-3
Genetic–exposome interactions and aging clocks in dementia: the ReDLat2 initiative
STAT+: Blood pressure tech floods the market after FDA relaxes wearables oversight
In early January, the Food and Drug Administration delivered on the Trump administration’s deregulatory promises by allowing more wellness products to be marketed without the agency’s authorization. Leaders at smart ring maker Oura swiftly planted the pivot foot.
“As soon as this guidance came out, literally the same day, we started having conversations with our product team around what our roadmap looks like, features that we could bring in and actually ship sooner,” Ricky Bloomfield, the company’s chief medical officer, told STAT less than a week after the FDA announcement. He added: “this guidance helps give us more confidence that we can release features sooner and not have to spend months getting additional clarification from the FDA.”
One thing FDA clarified in the updated guidance is that companies can release products that use sensors to “estimate, infer, or output” blood pressure and blood glucose readings without approval, if they are intended for wellness purposes. In a speech at the Consumer Electronics Show the day the guidance was announced, the FDA commissioner at the time, Marty Makary, said his agency would “get out of the way” of products that weren’t making medical or clinical claims. “This reduces the amount of subjectivity by regulators and guesswork by developers,” he said.
Five months later, consumer technology giants have already taken advantage. Oura on Thursday announced a refreshed model of its ring and a battery of new features, including two aimed at providing users with insights on blood pressure. In March, Samsung released a smartwatch feature that offers users readings of their systolic and diastolic blood pressure.
Elsewhere, upstart developers are racing to market with do-it-all devices. A smart ring called the Pin Pulse, which claims to offer readings of blood pressure, blood glucose, sleep insights, and more, raised $260,000 in a Kickstarter campaign that ended in April. The product was conceived by recent University of California, Berkeley graduate students who partially outsourced technical development to a team in China.
Optimistically, the new wave of blood pressure products may help raise awareness about a deadly hypertension epidemic, regulatory and clinical experts told STAT. After all, nearly half of American adults have high blood pressure, and many people have no idea until they have a heart attack. Realistically, experts are concerned that the underlying technology is still novel and unproven, and that a flood of confusing features may mislead users about the state of their health and prevent them from pursuing necessary care.
STAT+: An ASCO preview: What to watch for at cancer research’s big meeting
This is the online version of Adam’s Biotech Scorecard, a subscriber-only newsletter. STAT+ subscribers can sign up here to get it delivered to their inbox. STAT is also producing a free pop-up newsletter about this year’s ASCO meeting. Sign up here.
Chicago, here I come. The annual meeting of the American Society of Clinical Oncology kicks off tomorrow and runs through Tuesday, June 2.
Let’s set the table for cancer research’s big event, starting with the obvious headliner: Revolution Medicines and its RAS-blocking pancreatic cancer drug daraxonrasib. Full results from the company’s Phase 3 RASolute 302 study will feature prominently at ASCO’s plenary session on Sunday afternoon. The arena-sized exhibition hall will be jam-packed.