Psoriasis is a prevalent chronic inflammatory skin condition that is also classified as an autoimmune disorder. There is an established interplay between autoimmune diseases and mental health issues, particularly depression. Consequently, this study aims to explore the association between depression and psoriasis. This cross-sectional study examined data from participants in the National Health and Nutrition Examination Survey from 2009 to 2014. Depression information was gathered through the patient health questionnaire Patient Health Questionnaire-9 (PHQ-9). Weighted logic was applied to investigate the correlation between depression and psoriasis. In addition, subgroup analyses were conducted to investigate potential interactions. Out of the total 15,863 patients enrolled in the study, out of which 438 had a prior diagnosis of psoriasis. Weighted logistic regression analysis showed a direct relationship between the PHQ-9 result and psoriasis. Moreover, the occurrence of psoriasis was more prevalent among males compared to females in the case of depression. The restricted cubic spline curve demonstrated a positive linear correlation between psoriasis and depression, showing a turning point at 2. A subgroup examination was performed and revealed a connection between gender and depression. A significant positive relationship exists between the increase in PHQ-9 depression scores and the increased likelihood of having psoriasis, which varies among different genders.

Clozapine was (1) first introduced in Austria and Switzerland in 1972, (2) associated with 8 Finnish deaths due to agranulocytosis in 1975 (almost leading to its withdrawal), and (3) approved in the United States (US) for treatment-resistant schizophrenia in 1989 (resulting in a worldwide resurrection). This article reviews the 1960s/1970s trials published in German that brought about the first approval of clozapine; they are not included in PubMed and received no attention in previous historical articles. Prior historical manuscripts and the references of identified articles provide us with 13 early trials published in German. The first was unsuccessful. Randomization, double-blindness, and control antipsychotic agents were used in 1 of 10 single-center trials and a multicenter trial. Most trials focused on schizophrenia. The efficacy of clozapine in (1) mania was proposed by Angst in the Swiss trials, and (2) aggression across psychiatric diagnoses by an Austrian trial. These trials did not discuss titrations; a study by Blum and Mauruschat focused on physiological changes and first identified fever in the absence of infection during clozapine titrations (called benign hyperthermia in the US). These limited early trials leading to the introduction of clozapine in the 1970s in German-speaking countries produced many unresolved issues. Our discussion reviews the most important aspects that were clarified but not completely resolved in later years, including (1) risk of agranulocytosis, (2) titration and dosing, and (3) indications. Further clarifications and advances are limited by the lack of funding, as clozapine is a generic drug.

To validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH) and to assess its value as a real-time monitoring biomarker.

Pre-registered multicentre prospective observational cohort study.

Eight neurosurgical tertiary centres in Switzerland, Germany and Austria between August 2021 and June 2024.

366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days).

Daily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested.

CSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI) and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus and 3 month functional outcome.

CSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 µM, IQR 2.64 to 25.90) and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential for same-day SAH-SBI (area under the curve 0.59, 95% CI 0.56 to 0.63), with substantial between-centre heterogeneity. In a post-hoc exploratory analysis, higher CSF methaemoglobin showed a positive point-estimate of association with SAH-SBI (OR 1.18 per log(µM), 95% CI 1.02 to 1.36). Higher acute-phase EVD-derived CSF-Hb was associated with chronic hydrocephalus and a poor 3 month functional outcome. Catheter-related infection rates were low (2.2%).

In this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. Higher CSF methaemoglobin was associated with SAH-SBI; this hypothesis-generating observation requires prospective confirmation and motivates continued investigation of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates.

NCT04998370.

The hypothalamus comprises histologically and functionally distinct subunits critical to major depressive disorder (MDD) pathology; however, its localized neuroanatomical alterations in affected adolescents remain poorly understood. This study aimed to investigated volumetric changes in hypothalamic subunits among drug-naïve adolescents with MDD and explored their associations with clinical symptoms and sleep quality. High-resolution 3D T1-weighted MRI data from 83 drug-naïve adolescents with MDD and 59 matched healthy controls (HCs) were preprocessed and segmented into five bilateral subunits using FreeSurfer software. We investigated volumetric alterations in hypothalamic subunits and examined whether and how these structural changes accounted for the relationships between depressive severity and sleep quality. Adolescents with MDD showed significantly smaller volumes in the left anterior-inferior subunit (a-iHyp) and larger volumes in the right inferior tubular subunit compared to HCs. The volumes of the left a-iHyp were significantly negatively correlated with both sleep quality and depressive severity in adolescents with MDD. Furthermore, exploratory analysis indicated that the volumes of the left a-iHyp partially accounted for the associations between depressive severity and sleep quality. Additionally, the volumes of the left infTub were significantly negatively correlated with cognitive impairment scores in adolescents with MDD. These findings provide new insights into distinct hypothalamic subunit alterations in adolescents with MDD, and these insights enhance our understanding of the associations between subunit-level hypothalamic alterations and clinical symptoms in this clinical population.

Although fine particulate matter (PM_2.5) has been associated with cognitive dysfunction (CD), the roles of specific PM_2.5 components and potential mechanisms remain limited. This study aimed to examine the association of long-term PM_2.5 and its components with CD, identify the relative importance of components in the mixture, and generate hypotheses regarding possible biological pathways.

A total of 14,379 participants aged ≥ 60 from the Henan Rural Cohort were recruited. CD was assessed using the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS). Concentrations of PM_2.5, black carbon (BC), organic matter (OM), ammonium (NH₄⁺), sulfate (SO₄^2-), and nitrate (NO₃^-) were derived from the TAP dataset. Logistic regression and weighted quantile sum (WQS) regression were applied to estimate associations of single pollutants and pollutant mixture with CD. Network toxicology and machine learning analyses were performed to explore biological pathways and prioritize candidate genes.

For each interquartile range (IQR) increase in PM_2.5, BC, OM, NH₄⁺, SO₄^2-, and NO₃^-, the odds of CD increased by 19%-43%. BC consistently ranked as the leading contributor (weights: 86.38% to 54.31%), followed by OM (weights: 7.24% to 34.57%) across the four CD definitions. Network toxicology analysis identified 47 candidate PM_2.5-CD genes, and RPL23, RPL36AL, and RPS25 were prioritized as hypothesis-generating candidate genes by the random forest model (RF).

Long-term exposure to PM_2.5 and its components is associated with higher odds of CD in rural older adults. BC and OM may represent important contributors within the PM_2.5 mixture. Ribosomal and mitochondrial pathways may be dysregulated in PM_2.5-related neurotoxicity, but candidate genes require further validation.

Stress-related psychiatric disorders are increasingly common conditions that are notoriously difficult to treat. Identifying the factors that increase the risk of these conditions and defining the biological mechanisms through which they promote the development of these disorders could inform disease pathophysiology and reveal novel therapeutic strategies to improve mental health. Clinical findings suggest that oral antibiotics increase the risk of depression and anxiety, but preclinical studies have had mixed results. Administering antibiotics to rodents has been reported to induce depression- or anxiety-like behavior in some studies but to protect against stress-induced increases in depression- and anxiety-like behavior in others. The reasons for these discrepancies are unclear. The current study examined the effects of antibiotics on stress susceptibility in a model of sub-chronic stress in male and female c57BL/6 mice. Following exposure to oral antibiotics and/or stress, mice were tested in a panel of behavioral assays prior to their brains being examined for potential changes in hippocampal neurogenesis and microglial number. Overall, our results indicate that antibiotics increased susceptibility to stress in several assays, and some of these effects were more pronounced in females than males. Exposure to antibiotics also reduced the proliferation of progenitor cells in the hippocampus of unstressed, but not stressed, animals of both sexes but did not significantly impact the number of microglia or immature neurons in the hippocampus. Future work should examine additional potential mechanisms through which antibiotics impact stress susceptibility and behavior in males and females.

Stroke is a leading cause of disability, associated with impaired motor function and brain connectivity. Mental Simulation Practices (MSP), including Motor Imagery, Mirror Therapy and Action Observation Therapy, have been proposed as neurorehabilitation strategies capable of modulating neural networks. This review aimed to clarify the effects of MSP on brain connectivity using fMRI.

A PRISMA-based review was conducted and registered in PROSPERO (CRD420251086743). PubMed, Scopus and Web of Science were searched for randomized controlled trials published between 2015 and 2025 evaluating MSP-based rehabilitation versus conventional rehabilitation in stroke patients. Studies were included if they assessed fMRI-based connectivity changes before and after treatment. Meta-analysis was not performed because of heterogeneity in connectivity metrics and neuroimaging methodologies. Risk of bias was assessed using the Cochrane RoB 2 tool, showing low risk or some concerns.

Of 467 identified records, 8 randomized controlled trials involving 249 stroke patients met inclusion criteria. Most studies investigated Motor Imagery-based interventions, while two evaluated Mirror Therapy. Across studies, MSPs were consistently associated with upper limb motor improvement compared with conventional rehabilitation alone, accompanied by significant reorganization of brain networks. Neuroimaging findings demonstrated enhanced connectivity within sensorimotor regions, including the primary motor cortex, postcentral gyrus and inferior parietal lobule, together with modulation of corticospinal and interhemispheric pathways. Several studies also reported normalization of maladaptive activation patterns, reduced excessive sensorimotor connectivity and stronger interactions between motor and cognitive networks, changes correlated with clinical motor recovery. Additional reorganization involved attentional, visual and cognitive systems, suggesting network-level neuroplastic adaptations.

Mental simulation practices may represent promising adjunctive interventions in standard stroke rehabilitation programs, given their potential role in modulating brain connectivity.

The Terminally Ill Adults (End of Life) Bill was introduced for debate in UK Parliament in 2024. Notably, a disorder usually categorized as psychiatric and non-terminal-anorexia nervosa-became a focus. We sought to analyse key themes in this debate and explore implications. We searched transcripts of the UK Parliamentary debate for sections discussing eating disorders. We conducted a reflexive thematic analysis of these sections using methodology described by Braun and Clarke. Four themes were constructed during analysis. Three themes related to conceptual boundaries used to define eligibility for Physician Assisted Death: (1) terminality, (2) capacitous consent, and (3) the distinction between mental and physical disorder. The fourth theme was: Population impact of permitting Physician Assisted Death. Several speakers framed eating disorders as a 'red herring' in the debate on Physician Assisted Death. Others argued that eating disorders exemplified how proposed eligibility criteria for Physician Assisted Death could be interpreted in ways that extend beyond their intended scope. In this way eating disorders functioned as a canary in the coal mine. We conclude that considering complex examples such as eating disorders is not a distraction but offers important opportunities to stress test seemingly intuitive eligibility criteria for Physician Assisted Death.

Well-being is a central dimension of recovery in severe mental disorders (SMD), underscoring that mental health extends beyond the absence of illness. However, well-being may not hold the same meaning for patients, relatives, and professionals, raising key questions about its assessment in clinical practice. Moreover, the perception of well-being is a decisive outcome that can guide clinical decision-making, reinforcing its role as a critical indicator in psychiatric care.

This sequential mixed-methods study examined agreement between 186 patients with SMD (self-informants) and 186 external informants (family, friends, or therapists) on the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Quantitative analyses assessed concordance and tested whether age, gender, relationship type, or relationship duration predicted discrepancies. Complementary qualitative interviews explored how each group conceptualizes well-being.

Quantitative analyses showed moderate concordance between self- and external informants (70%), with professionals tending to rate well-being higher than relatives and patients. Relationship type explained only a small proportion of variance. Qualitative findings indicated that patients primarily linked well-being to experiential recovery processes such as empowerment, freedom, and acceptance, whereas external informants, particularly professionals, focused on observable and behavioral aspects, including self-efficacy and help-seeking.

Well-being is understood differently by stakeholders. Patients emphasize internal, subjective dimensions, while relatives and professionals prioritize behavioral indicators. These complementary but divergent perspectives highlight that self-reports capture unique aspects of well-being not reflected in proxy assessments. Clarifying what well-being means for each agent is essential for individualized rehabilitation planning and ensuring clinical decisions align with patients' recovery goals.