Context-dependent interaction between oxytocin gene polymorphisms and alcohol dependence in modulating negative emotions during acute alcohol withdrawal in adult males

ObjectiveThe importance of multiple gene-environment interaction (G × E) has been highlighted in understanding the etiology of negative emotions. This study examines the impact of oxytocin (OXT) polymorphisms (rs2740210, rs6133010, and rs2740209) in combination with alcohol dependence on anxiety and depression symptoms during acute alcohol withdrawal under different social and environmental contexts.MethodA total of 414 Chinese Han male adults undergoing acute alcohol withdrawal were recruited. Participants provided blood samples for genotyping, self-reported measures of depression and anxiety, assessments of alcohol dependence severity, and demographic information regarding social and environmental contexts.ResultsResults revealed a positive correlation between severity of alcohol dependence and symptoms of depression and anxiety, while oxytocin polymorphism did not have a direct effect on depressive and anxiety symptoms. A significant interaction between OXT polymorphism (rs2740210 and rs2740209) and alcohol dependence in relation to anxiety symptoms solely among adults living with family and/or those who were married was observed. Further analyses indicate that the GG and CC genotypes are risk genotypes, while the T allele (rs2740210) and G allele (rs2740209) are non-risk alleles in the interaction between OXT genotypes (rs2740210, rs2740209) and alcohol dependence on anxiety among the aforementioned participants.ConclusionsThese findings provide evidence for distinct G × E interaction effects on anxiety and depression symptoms during acute alcohol withdrawal, supporting the weak diathesis-stress model. Furthermore, the study highlights the importance of considering environmental factors when investigating the role of oxytocin as a biological substrate underlying social bonding and the regulation of negative emotions.

Validation of a criterion-based screening and triage pathway for adult ADHD: a prospective observational study of safety and operational efficiency

BackgroundThe increasing demand for adult attention-deficit hyperactivity disorder (ADHD) assessments has required the development of efficient triage pathways. This study provides a formal assessment of a criterion-based screening model designed to prioritise patient safety and operational efficiency within a National Health Service (NHS) specialist secondary care setting.MethodsA prospective observational validation design was employed, involving 49 consecutive adults referred for ADHD assessment none of whom had a previous ADHD diagnosis. The Comprehensive ADHD Screening Questionnaire (CASQ), a clinician-administered instrument based on DSM-5 criteria, was utilised by four trained Physician Assistants. To ensure an assessment of triage safety, a universal assessment model was adopted: all participants received a blinded, gold-standard diagnostic assessment (NICE-compliant) regardless of the initial triage recommendation thereby eliminating verification bias. The primary outcome measure was the Number Needed to Harm (NNH), defined as the number of people screened before a single false-negative result occurs.ResultsOf the 48 participants who completed the diagnostic process, six (12.5%) received an ADHD diagnosis. The triage pathway correctly identified all six cases, resulting in a sensitivity of 100.0% (95% CI: 61.0%–100.0%) and an infinite NNH. Specificity was 45.2% (95% CI: 31.2%–59.9%), with a positive predictive value of 20.7%. The pathway permitted 39.6% (n = 19) of referrals to be triaged to alternative pathways rather than full ADHD assessment, potentially saving significant specialist clinician time. Exploratory analyses indicated that score magnitude did not reliably distinguish between true and false positives within the group triaged as appropriate for further assessment.ConclusionsThese preliminary findings suggest that criterion-based screening conducted by appropriately trained non-specialist clinicians can achieve high levels of safety whilst improving service efficiency. The findings support the feasibility of task-shifting models in adult ADHD services, provided that triage thresholds are calibrated to prioritise sensitivity. These results require replication in adequately powered multi-site studies before firm conclusions regarding pathway safety can be drawn. Further research is required to establish inter-rater reliability and cost-effectiveness across diverse clinical settings.

Protracted encephalopathy and subacute combined degeneration associated with chronic nitrous oxide use: a case report

Nitrous oxide is a dissociative hallucinogen that is increasingly used recreationally, in part due to its widespread availability. Its use is known to cause subacute combined degeneration via inactivation of vitamin B12; it may also result in acute delirium and chronic progressive encephalopathy. Though current practice guidelines call for treatment of neurological sequelae of nitrous oxide use with vitamin B12 supplementation, a paucity of long-term outcome data limits our ability to guide extended courses of treatment. In this report, we discuss a case of protracted encephalopathy associated with nitrous oxide use. We track the response to vitamin B12 supplementation in the hospital setting using the Mini-Mental Status Exam to assess the severity and improvement of cognitive impairment. We also review the patient’s comorbid medical and psychiatric conditions, which complicate diagnosis and treatment planning in this patient population.

Parsing autism spectrum heterogeneity through fMRI

Nature Neuroscience, Published online: 15 May 2026; doi:10.1038/s41593-026-02269-1

Autism is remarkably heterogeneous, posing a long-standing challenge for linking genetics to brain dynamics. A cross-species study identifies two principal dysconnectivity signatures across 20 mouse models of autism risk, each associated with distinct molecular pathways, and shows analogous connectivity patterns in autistic humans. These results establish a translational framework for biologically grounded fMRI phenotyping.

Family psychoeducation to support patients with psychotic illness: two-year outcomes from a pre–post longitudinal pilot study

BackgroundPsychoeducation for families of young adults with psychosis is an evidence-based intervention that alleviates carer burden. The implementation of programming is limited, leaving family carers shouldering a heavy burden without appropriate support.ObjectiveThis pre-post longitudinal pilot study evaluated the preliminary outcomes of a psychoeducational group intervention for family carers of young adults with psychosis, aimed at building skills and reducing carer burden to support recovery in their loved ones.MethodsThe intervention, co-developed and co-facilitated by healthcare professionals and individuals with family lived experience, was delivered in Edmonton, Canada. Participants (n= 13) completed the Family Burden Interview Schedule (FBIS) at pre-intervention, post-intervention, and at 6, 12, and 24-month follow-up. Linear mixed models assessed burden scores over time.ResultsThe overall model of total burden did not reach statistical significance. Exploratory post-hoc comparisons indicated a significant total burden reduction from pre-intervention to 6-months (p = 0.032), with no other significant changes. The overall family interaction burden subscale model showed no significant effect of time. Exploratory post-hoc analyses indicated a decrease in family interaction burden from pre- to post-intervention (p = 0.026) and to 6- months (p = 0.032), with no other significant changes.ConclusionThis pilot study provides preliminary and hypothesis-generating findings suggesting a co-produced, skills- and knowledge-based psychoeducational intervention may be associated with reductions in carer burden, particularly in the domain of family relations. Given the small sample size, further research with sufficient statistical power is warranted to evaluate the long-term impact and accessibility of the intervention and inform its integration into early psychosis care.

[Comment] How much is enough in ADHD pharmacotherapy?

The evidence base for ADHD pharmacotherapy has answered one question more confidently than any other: whether medications are effective, on average, in reducing core ADHD symptoms. We know that several stimulant and non-stimulant treatments, including methylphenidate, amphetamines, atomoxetine, and guanfacine, improve symptoms at the patient-group level.1 What has remained harder to identify is where titration should stop: the point at which further dose escalation is unlikely to yield meaningful additional benefit and might instead worsen tolerability.