Childhood maltreatment (CM), particularly emotional neglect and abuse, has been associated with an increased risk of anxiety and less favorable psychotherapy outcomes in adulthood. Impairments in personality functioning are a significant mechanism mediating this relation. This naturalistic cross-sectional study examined the mediating role of personality functioning in the relation between CM and anxiety symptoms in a clinical adult sample. A total of 335 adult patients starting individual psychotherapy completed intake self-report questionnaires about CM experiences, personality functioning, and anxiety symptoms. We assessed the two dimensions of personality functioning described in Section III of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), specifically, self-functioning and interpersonal functioning. Bootstrapped mediation analyses were conducted to evaluate the mediating role of personality functioning in the association between each CM type and anxiety symptoms. 64.2% of the sample reported at least one type of CM. Personality functioning explained 73% of the total effect of CM on anxiety symptoms. Only emotional abuse and emotional neglect showed significant total effects. Emotional abuse retained a direct effect, while emotional neglect was fully mediated by personality functioning. Both personality functioning dimensions were significant mediators, yet self-functioning had a larger impact. Psychotherapeutic interventions targeting impairments in personality functioning are essential for treating anxiety symptoms in adults with CM. Findings emphasize the importance of trauma-informed, personalized interventions, and CM prevention strategies.

Obsessive-compulsive disorder (OCD) is characterized by widespread executive function impairments linked to disrupted fronto-striatal circuits. Ablative therapies such as capsulotomy show promise efficacy in treatment-refractory OCD, yet their effects on executive neural substrates remain poorly understood. This study explores how OCD and capsulotomy influence executive prefrontal function. Twenty-three post-capsulotomy OCD patients, thirty OCD controls, and thirty-two health controls (HC) were recruited in the study. Post-capsulotomy patients were recruited at least 6 months following surgery to allow for post-operative stabilization. Participants completed three executive function tasks assessing distinct cognitive domains: the Extra-Dimensional Intra-Dimensional (EDID) task testing set-shifting, the N-back task testing working memory and flanker task measuring conflict processing. The EDID and N-back tasks were administered during concurrent task-based fMRI, while the flanker task provided only behavioral measures. In the EDID task, OCD capsulotomy patients demonstrated greater post-error flexibility towards ID versus ED shifting relative to both OCD controls and healthy controls, despite exhibiting more ED errors. OCD controls showed less shifts after errors compared to HC, which was not revealed in the capsulotomy group. OCD patients showed less neural differentiation between ED versus ID in lateral and mesial prefrontal regions relative to HC. Capsulotomy was associated with decreased pre-supplementary motor area activity to ED shifts compared to HC, indicating impairments in neural reactivity to ED shifting. No evidence supported the influence of capsulotomy in the n-back or the flanker task. Specifically, both OCD groups showed impaired working memory performance at high memory load along with dysfunction in the whole frontoparietal network. In the flanker task, impairment in dissociating congruent and incongruent conditions were found in both OCD groups but not in the HC group. These findings suggest capsulotomy specifically remediates error-monitoring and behavioral flexibility through mesial prefrontal remodeling, while leaving working memory and conflict processing deficits intact. This dissociation implies that cognitive flexibility may represent a state-dependent process amenable to intervention, whereas working memory and conflict processing impairments may reflect trait markers of OCD vulnerability. These results have clinical implications on relative safety profile of capsulotomy and patient selection for precision neuromodulation.

Schizophrenia (SCZ) is frequently accompanied by peripheral immune dysregulation, yet robust and reproducible blood-based molecular markers remain limited.

We sought a compact long non-coding RNA (lncRNA) signal in peripheral blood leukocytes (PBL) and examined how it aligns with immune-linked transcriptional programs and cellular compartments, using bulk RNA sequencing (RNA-seq), targeted validation, and a healthy-donor peripheral blood mononuclear cell (PBMC) single-cell reference for localization.

PBL from 50 first-episode or unmedicated SCZ patients and 50 matched controls underwent RNA-seq. We performed reference-guided transcript annotation and generated lncRNA and mRNA count matrices. Differential expression was assessed with edgeR (TMM normalization). Candidate lncRNAs were prioritized using sample-level lncRNA-mRNA co-variation, followed by qRT-PCR validation in an independent cohort and evaluation with a two-feature logistic regression model using repeated 10-fold cross-validation. Pathway-scale analyses and weighted gene co-expression network analysis (WGCNA) summarized coordinated programs. Single-cell data from healthy donors were used for expression localization only, not case-control testing.

We observed a small set of dysregulated lncRNAs alongside broader mRNA changes. Two candidates at the CCR3 and IL1RAP loci (TCONS_00134168/lncRNA-CCR3 and TCONS_00138311/lncRNA-IL1RAP) showed consistent case-control directionality and were supported by qRT-PCR. The two-lncRNA model showed strong internal discrimination (AUC = 0.933) but weaker, uncertain performance in a small external qRT-PCR set (AUC = 0.656). Enrichment analyses highlighted synapse-related annotations, RNA processing/translation, and immune signaling, with recurrent involvement of IL1RAP-linked IL-1 branches. WGCNA placed lncRNA-IL1RAP and IL1RAP within diagnosis-inversely associated co-expression programs, whereas lncRNA-CCR3 showed a more transcript-specific pattern. In the healthy-reference single-cell atlas, IL1B/IL1RAP/HSF1 signals were most prominent in the monocyte/macrophage compartment.

Together, these findings support an exploratory two-lncRNA candidate marker concept, while underscoring the need for larger multi-center validation and targeted mechanistic follow-up without implying causality.

Mismatch negativity (MMN) is a neural response to unexpected deviations from a regular sequence of stimuli. A diminished MMN is highly replicated in schizophrenia; however, whether this is observed in bipolar disorder (BD) is less clear.

To conduct a meta-analysis of MMN alterations in people with BD compared to healthy controls.

Electronic databases were searched until 20/10/2025, for between-subjects studies examining MMN amplitudes and or latencies in BD patients compared with controls. 15 studies consisting of 437 BD patients and 815 controls were included in this analysis.

The primary outcome was the difference in MMN amplitude between the BD and control groups, from studies using standard MMN paradigms. Meta-analysis revealed diminished MMN amplitudes (n = 14) in BD versus controls (standardised mean difference = 0.47, 95% confidence interval [0.28, 0.66], p < 0.0001). Exploratory secondary meta-regressions revealed no significant relationship between MMN amplitude and age, sex, symptoms, or illness duration. Subgroup analyses revealed MMN amplitude group difference for paradigms using duration versus frequency deviants.

MMN amplitude deficits are observed in bipolar disorder. As MMN deficits are consistently observed in schizophrenia, whether the MMN deficits observed in BD relate to psychotic symptoms or specific BD subtypes remains unclear. Limitations of this meta-analysis include low study numbers for some of the meta-regressions. Most included studies did not separate bipolar subtypes; therefore, it was not possible to determine whether the observed effects relate to affective or psychotic symptoms. Future research should distinguish putative BD subtypes and include measures of symptoms to clarify the potential of MMN as a clinical marker to guide treatment decisions.

Classical serotonergic psychedelics (e.g., LSD, psilocybin, DMT) alter perception and neuroplasticity primarily via 5-HT2A receptor activation and downstream Ca²⁺-dependent signaling cascades. Here we propose a speculative yet falsifiable pharmacological hypothesis that these drug-induced biochemical cascades might interface with quantum-mechanical processes in the brain. We focus on nuclear spin dynamics in phosphate-containing biomolecules-calcium phosphate nanoclusters known as "Posner molecules" (Ca₉(PO₄)₆) - as a candidate substrate for quantum coherence and entanglement in neural tissue. We distinguish the metaphorical "classical" analogies in psychedelic neuroscience from a literal quantum-level mechanism involving nuclear spin coherence and entanglement. The central hypothesis is that intense 5-HT2A-driven neural activity and Ca²⁺ flux during psychedelic exposure foster conditions under which ³¹P nuclear spins in phosphate groups may become entangled and shielded from decoherence within Posner molecules and subsequently influence neuronal signaling when these clusters dissolve and release bursts of Ca²⁺ in different neuronal compartments. Building on Fisher's Posner model of quantum cognition, we reframe Posner molecules as a potential quantum-coherence nexus in psychedelic action, de-emphasizing earlier microtubule-centric models and explore how such quantum effects, if they exist, might influence pharmacological outcomes. We outline translational implications of this hypothesis, including potential insights into inter-individual variability in treatment response and novel experimental paradigms for psychiatry. To ensure falsifiability, we propose concrete experimental directions in the short term (isotopically modified psychedelics and xenon environments), medium term (advanced quantum sensors such as nitrogen-vacancy magnetometry and ultrafast spectroscopy), and long term (entangled ligand studies or quantum neuroimaging modalities). While speculative, this interdisciplinary framework generates specific, disprovable predictions. Confirming or refuting the role of quantum-mechanical phenomena in psychedelic neuropharmacology would profoundly impact our understanding of mind-brain relationships and encourage high-reward innovation in psychiatric treatment and brain-targeted drug design.

Diversity of the multiple sclerosis (MS) population in Canada is unknown, yet demographic and diversity-related characteristics influence health outcomes.

To determine "What strategy would best address the information gaps regarding diversity of the MS population in Canada?"

The virtual nominal group technique involved silent idea generation, recording and discussion of items, preliminary voting, discussion and final ranking.

Eight participants proposed 10 strategies; two were dropped before final voting, after which the top options (tied) were: a national standardized clinic form, novel applications of administrative data, and novel data linkages.

We identified strategies to characterize the diversity of the MS population in Canada.

The NOTCH3-SVD staging system was developed to characterize NOTCH3-related small vessel disease (SVD), but it has not been validated in cohorts carrying a single pathogenic variant. We applied this system to Taiwanese individuals with the NOTCH3 p.R544C variant to evaluate its clinical relevance and prognostic value.

We enrolled individuals carrying the NOTCH3 p.R544C variants from 2 sources: the Taiwan Precision Medicine Initiative, a hospital-based volunteer cohort undergoing genetic screening, and the Taiwan CADASIL Registry, which includes individuals with symptomatic SVD and confirmed NOTCH3 pathogenic variants. Participants were classified using the NOTCH3-SVD staging system, ranging from stage 0 (premanifest stage) to stage 4B (end stage). Baseline characteristics were compared across stages. Multivariable models were used to identify factors associated with prior stroke or cognitive impairment. Stroke-free survival was analyzed using Kaplan-Meier curves and Cox proportional hazards models. Cognitive decline, assessed by Mini-Mental State Examination, was evaluated using a generalized estimating equation.

Among 260 individuals (median age 62 years; 49% male), the median stage was 2A. Higher stages were positively associated with prior stroke, cognitive impairment, gait disturbance, and psychiatric symptoms and inversely associated with headache (all p values < 0.05). Fewer years of education (OR 0.90, 95% CI 0.83-0.98, p = 0.012), hypertension (OR 2.34, 95% CI 1.18-4.67, p = 0.016), and higher NOTCH3-SVD stage (OR 3.70 per 1-substage increase, 95% CI 2.61-5.25, p < 0.001) were significantly associated with prior stroke or cognitive impairment. During a median follow-up of 1.9 years, individuals with stage ≥2B had a higher risk of incident stroke than those with stage <2B (annual risk 6.7% vs 2.0%, log-rank p = 0.023; adjusted hazard ratio 3.38; 95% CI 1.10-10.4, adjusted for age and hypertension). MMSE scores declined progressively over 2 years in individuals with stage ≥2B, whereas those with stage <2B remained cognitively stable (p for interaction = 0.024).

The NOTCH3-SVD staging system effectively stratified disease burden and predicted incident stroke and cognitive decline in individuals with NOTCH3 p.R544C, with stage ≥2B indicating a higher risk.

This single-center retrospective study aims to analyze the clinical characteristics, treatment strategies, and outcome at discharge of neonatal-onset herpes simplex virus encephalitis (NHSE).

We conducted a single-center retrospective case review of infants diagnosed with NHSE at the Children's Hospital of Fudan University between February 1, 2016, and February 1, 2024. Clinical data, including demographics, clinical symptoms, laboratory findings, neuroimaging results, treatment regimens, and outcomes at discharge, were collected and analyzed.

A total of 14 infants with NHSE (7 males, 7 females) were identified at our center, with a median age at diagnosis of 26 days (range: 7-51 days). Initial symptoms predominantly included fever and seizures, with neurological involvement (e.g., seizures, lethargy, irritability or altered mental states) in 13 cases. Physical examinations, such as bulging anterior fontanel, were noted. Herpes simplex virus (HSV)-DNA was detected in 13 cases (6 HSV-1, 7 HSV-2) through cerebrospinal fluid (CSF) polymerase chain reaction (PCR) or metagenomic testing. Among these, 9 cases were identified via CSF-PCR, with 7 testing positive on the initial examination and 2 on repeated testing. Notably, 6 cases were diagnosed using metagenomic next-generation sequencing (mNGS), all of which yielded positive results on the first test. Ten out of the 12 children often exhibited temporal lobe spikes on video electroencephalograms (VEEGs). Early magnetic resonance imaging (MRI) revealed cytotoxic edema, progressing to multicystic encephalomalacia. All received acyclovir antiviral treatment. Seven discontinued treatments, one was referred for ocular lesions, and six improved and were discharged.

In this single-center cohort, NHSE often presents with nonspecific fever and seizures, with late onset and absent indicative rashes, complicating early diagnosis. For newborns suspected of having NHSE, early CSF HSV-DNA testing and prompt antiviral treatment are essential to improve outcomes. Metagenomic sequencing is especially valuable for accurate, rapid diagnosis when conventional methods fail.

Craving and maladaptive choices are intertwined across addictive disorders, yet the specific computational mechanisms mediating their interactions remain elusive. Here we tested a hypothesis that momentary craving and reinforcement learning influence each other during substance-related decision-making. Two substance-using groups with moderate to high addiction risk levels (alcohol drinkers and cannabis users; total n = 132) performed a decision-making task in which they received a group-specific addictive cue or monetary outcomes and reported moment-to-moment subjective craving. Computational modeling revealed that momentary craving biased substance-specific learning rate in both groups, but in opposite directions. In addition, expected values and outcomes jointly influenced elicited craving across groups and decision contexts. Finally, regressions incorporating model-derived parameters best predicted alcohol, but not cannabis, addiction risk scores, supporting the selective utility of using these model-based parameters in making clinical predictions. Together, these findings provide a computational framework that accounts for the interaction between craving and maladaptive choices across addictive domains.

The adoption of remote consultations following the COVID-19 pandemic raised questions about the impact on patient outcomes. Here we assess the relationship between the proportion of remote consultations in primary care and subsequent acute mental health service use, specifically emergency contacts with mental health liaison teams, psychiatric hospital admissions, inpatient bed-days and compulsory admissions under the Mental Health Act. We conducted a retrospective cohort study of patients diagnosed with depression, anxiety or severe mental illness using the Clinical Record Interactive Search platform, which accesses pseudonymized electronic patient records from a large London mental healthcare provider. These records were linked to primary care consultation data from the Lambeth DataNet platform. The study period covered 1 January 2019 to 31 December 2021, spanning prepandemic and pandemic phases. Associations were estimated using generalized estimating equations with a negative binomial distribution to account for overdispersion and clustering by general practice. Multiple imputation by chained equations was used to address missing data. The analytic cohort included 107,993 patients. A higher proportion of remote consultations was associated with a modest increase in the rate of emergency contacts with mental health liaison teams (incidence rate ratio (IRR) 1.04, 95% confidence interval (CI) 1.01-1.07 per 10-percentage-point increase in remote care). By contrast, no significant associations were found between consultation modality and psychiatric hospital admissions (IRR 1.03, 95% CI 1.00-1.07), inpatient bed-days (IRR 1.02, 95% CI 0.95-1.09) or compulsory admissions (IRR 1.03, 95% CI 0.99-1.07). Patients who used remote primary care consultations more frequently, particularly those delivered via telephone, had more emergency contacts with mental health liaison teams, potentially reflecting precautionary referrals or reverse causality. However, remote consulting was not associated with increased psychiatric admissions, longer hospital stays or compulsory detentions, suggesting it is not linked to clinical deterioration requiring hospitalizations.