Depression represents a major global disease burden. High-altitude hypoxia is closely associated with an increased incidence of depressive symptoms; however, the underlying mechanisms remain unclear. In this study, mice were subjected to 7 days of hypoxic exposure simulating high-altitude environments at 3000 m (14.4% O2) and 4000 m (12.7% O2). Depressive-like behaviors were assessed using the open field test, tail suspension test, and forced swim test. Enzyme-linked immunosorbent assays were employed to measure markers related to inflammatory responses, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis activity. Additionally, 16S ribosomal RNA sequencing was performed to analyze alterations in the gut microbiota. Untargeted metabolomics was used to examine metabolite changes in the colon and hippocampus. Validation analyses included measurements of hippocampal immunofluorescence density and cortical neurotransmitter levels. Hypoxic exposure induced depressive-like behaviors, as well as colonic and hippocampal tissue damage. It also exacerbated inflammation and oxidative stress, reduced gut microbiota diversity, disrupted tryptophan metabolism, decreased cortical neurotransmitter levels and brain-derived neurotrophic factor (BDNF), and increased the immunofluorescence density of hippocampal neuron-glial antigen 2 and oligodendrocyte transcription factor 2. These effects exhibited an intensity-toxicity relationship. Acute hypoxia is associated with gut microbiota imbalance, disrupted tryptophan metabolism, inflammatory responses, and dysfunction of the HPA axis, alongside negative emotional states. These multidimensional alterations are strongly correlated, suggesting a potential regulatory network involving the gut microbiota-tryptophan metabolism axis in hypoxia-induced emotional changes.

Vitamin D deficiency is prevalent among individuals with depression; however, clinical findings regarding this association have been inconsistent. Additionally, a significant proportion of depressed patients present with dyslipidemia, yet the interplay between vitamin D status, lipid metabolism, and depression remains poorly understood. We aimed to explore the role of vitamin D in depression and to investigate the potential associations between vitamin D status, lipid metabolism, and depressive symptoms. We recruited 412 first-episode, drug-naïve patients with depression and 180 age-matched healthy controls. Fasting venous blood samples were collected in the morning to quantify serum vitamin D and lipid profiles. Depressive symptoms were assessed on the day of blood collection using both the Patient Health Questionnaire-9 (PHQ-9) and the 17-item Hamilton Depression Rating Scale (HAMD-17). Spearman's rank correlation was employed to examine associations between serum vitamin D concentrations and depressive symptom severity. Binary logistic regression analysis was subsequently performed to identify potential risk factors for depression. Compared with healthy controls, depressed patients had significantly lower serum vitamin D and high-density lipoprotein cholesterol (HDL-C) levels. This sex-specific pattern showed that male patients had lower vitamin D, while female patients had lower HDL-C. Spearman's correlation analysis revealed significant inverse correlations of vitamin D and triglyceride (TG) with PHQ-9 and HAMD-17 scores among depressed patients. Logistic regression analysis indicated that individuals with higher vitamin D levels had a reduced likelihood of depression compared with those with low vitamin D levels (adjusted odds ratio (OR) = 0.950, 95% confidence interval (CI): 0.920-0.982, p = 0.002). Similarly, subjects with elevated HDL-C levels were associated with a lower likelihood of depression relative to those with diminished HDL-C levels (adjusted OR = 0.317, 95% CI: 0.173-0.583, p < 0.001). Serum vitamin D and HDL-C levels were lower in patients with depression than in healthy individuals. Both vitamin D and HDL-C may be inversely associated with depression.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Early identification of high-risk infants is crucial for intervention and long-term outcomes. This study explored the association between early neurological development from 12 to 15 months and the related risk factors for ASD, with a primary focus on M-CHAT status at 24 months as the screening outcome, and the impact of family history, prematurity, and sleep disorders. We conducted a retrospective analysis of 50 children aged 24 months who tested positive on the Modified Checklist for Autism in Toddlers (M-CHAT) and 50 matched controls with negative results. Neurodevelopmental status was assessed using the Gesell Developmental Diagnosis Scale (GDDS), the Peabody Developmental Motor Scales, Second Edition (PDMS-2), and the Sensory Integration Schedule (SIS). Statistical analyses, including logistic regression, were used to evaluate associations among baseline characteristics, neurodevelopmental scores, and ASD risk factors. A total of 100 infants were included, with 50 classified as high risk and 50 as low risk. High-risk infants had significantly higher rates of family history of ASD, prematurity, and sleep disorders. They showed impairments across several PDMS-2 subscales, including stationary, locomotion, and grasping, as well as GDDS subscales such as adaptability and language. Logistic regression analysis revealed that neurodevelopmental impairments were significantly associated with M-CHAT positivity at 24 months. Early neurodevelopmental impairments in infants aged 12 to 15 months may serve as important indicators of ASD risk. Identifying these factors may facilitate timely intervention and improve outcomes for high-risk children.

The cerebellum is a critical node implicated in the pathology of schizophrenia. Previous studies have demonstrated that dance interventions can enhance cerebellar functional connectivity in healthy individuals. These findings suggest that dance intervention might represent a promising treatment for patients with schizophrenia. A total of 32 patients with schizophrenia were randomly assigned to two groups: a dance group (n = 18) and an aerobic exercise group (n = 14). Clinical symptoms and cognitive function, along with resting-state functional magnetic resonance imaging (fMRI) data, were collected from all participants at baseline and post-intervention. The cerebellar motor (CBCm) and cerebellar cognitive (CBCc) regions were defined for the calculation of dynamic functional connectivity (dFC). Repeated-measures analyses of covariance (ANCOVAs) were conducted for statistical analysis. Significant interaction effects were observed for cognitive function and dFC. Dance intervention specifically enhanced cognitive function, as assessed by the Continuous Performance Test-Identical Pairs (CPT-IP) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Moreover, increased dFC was observed between the CBCm and the left medial superior frontal gyrus, left superior occipital gyrus, and right cuneus, as well as between the CBCc and the right median cingulate cortex and the left inferior temporal gyrus in the dance intervention group. Additionally, dFC between the CBCc and the median cingulate gyrus showed a positive correlation with CPT-IP (r = 0.412, p = 0.026) and HVLT-R (r = 0.414, p = 0.021) scores. These findings suggest that dance intervention specifically enhances cerebellar connectivity patterns, potentially improving attention and verbal memory in patients with schizophrenia. No: ChiCTR2100049273, https://www.chictr.org.cn/showproj.html?proj=65597.

NCT06524505. Registered 23 July, 2024, https://clinicaltrials.gov/study/NCT06524505.

Background: Deficits in visual working memory (vWM) represent a core cognitive impairment in schizophrenia; however, the dynamic spatiotemporal characterization of their underlying neural mechanisms remains unclear. The present study employed multivariate pattern classification (MVPC) and searchlight analysis to investigate neural signaling differences between patients with schizophrenia (PSZ) and healthy control subjects (HCS) during a vWM task. Methods: A total of 46 participants (22 PSZ, 24 HCS) completed a change detection task comprising three conditions: two targets, zero distractors (2T0D); two targets, two distractors (2T2D); and four targets, zero distractors (4T0D). Contralateral delay activity (CDA) was extracted through event-related potential (ERP) analysis. MVPC was applied in the temporal dimension, while a searchlight approach was employed in the spatial dimension to decode memory load (2T0D/2T2D/4T0D) and memory side (left/right) information. Results: CDA amplitude was significantly reduced in the PSZ group, particularly in the 2T2D condition (p = 0.01), indicating that the scope and control of attention elicited comparable CDA amplitudes. MVPC analysis revealed that decoding accuracy in the PSZ group was significantly lower than in the HCS group during the time window of 93–652 ms (pcorrected &lt; 0.05), suggesting diminished efficiency of neural information encoding during the delay period. The searchlight analysis identified the most pronounced decrease in decoding accuracy within the left parietal region in the PSZ group, consistent with the hypothesis of abnormal functional connectivity in the inferior parietal gyrus (IPG). Conclusions: This study reveals the spatiotemporal dynamics of vWM deficits in schizophrenia, characterized by ERP decoding technology. It offers a novel target for the development of neuromarker-based cognitive interventions.

This opinion piece primarily targets health and ancillary professionals, but it is also intended to serve as an unbiased guide for policymakers and legislators worldwide. It calls for the protection of human rights and advocates for evidence-based, inclusive health and socio-legal policies for all, regardless of gender identity. The article clarifies the distinctions between biological sex, sexual orientation, and gender, and critically examines and refutes the growing misconception that recognizing diverse gender identities is a political matter rather than a medical and human rights issue. In fact, gender diversity has existed across cultures for millennia. A major concern addressed in this piece is how societal norms expose transgender and gender non-conforming (TGNC) persons to stigma, discrimination, and social exclusion. The focus, however, is on the heightened vulnerability of TGNC individuals, particularly those from marginalized groups (for example, immigrants, individuals with low socio-economic status, non-White populations), to mental health conditions such as depression, anxiety, eating disorders, substance misuse, and suicidal ideation. Young TGNC persons and those with intersecting marginalized identities (for example, migratory background, socio-economic disadvantage, skin color) are especially susceptible to victimization. Many of these difficulties are exacerbated by discrimination, lack of legal protections, and societal prejudice. The article also addresses disparities in TGNC rights and protections across different regions, with the highest levels in Western Europe and North America and the lowest in the Middle East and Africa, and highlights how the scarcity of robust TGNC research in the Global South may adversely affect the health and well-being of TGNC individuals in those regions. The authors propose eight actionable recommendations to improve mental health outcomes for gender minorities: (i) collecting more nuanced data that distinguishesdifferentiates TGNC people from other sexsexual and gender minorities (under the Lesbian, Gay, Bisexual, Transgender, Queer + umbrella); (ii) fostering dialogue and research to counter misinformation about TGNC persons; (iii) incorporating gender diversity into early education; (iv) promoting human connectedness and social support; (v) developing inclusive mental healthcare services; (vi) improving professional training on gender diversity; (vii) establishing centres specializing in gender medicine; and (viii) banning harmful practices such as gender identity conversion efforts. The importance of cultural sensitivity when implementing these recommendations is emphasized.

Clinically complex adults referred to ECT for depression presented with prominent memory concerns and performed below expectation compared to their estimated premorbid cognitive functioning at baseline. Naturalistic delivery of ECT did not appear to be associated with prolonged adverse cognitive outcomes; however, subjective memory concerns and below-expected cognitive performance persisted during follow-up. Treatment response impacted subjective memory outcomes, with only 'Responders' endorsing slightly reduced, though still persistent, subjective memory concerns following ECT. Conclusions on the long-term impacts of ECT are tempered by the high lost to follow up (LTFU) rate observed across follow-up assessments (66% LTFU at 6-months, 81% LTFU at 12-months). Nonetheless, these findings emphasize the need to address subtle cognitive deficits and memory complaints that persist following ECT, even in individuals demonstrating clinical improvement.

Background: Schizophrenia primarily depends on pharmacotherapy, which has demonstrated limited efficacy in enhancing cognitive impairments. High-definition transcranial direct current stimulation (HD-tDCS) and computerized cognitive remediation therapy (CCRT) hold potential for improving cognitive impairments. This study aims to investigate the effects of combining HD-tDCS with CCRT on cognition and to explore the mechanisms of this approach in schizophrenia. Study Design: This is the protocol of a randomized controlled trial. Methods: Schizophrenia patients will be randomly assigned to one of 4 groups: HD-tDCS + CCRT group (Group 1), HD-tDCS group (Group 2), CCRT group (Group 3), and a control group (Group 4). The central electrode will be personalized using magnetic resonance imaging (MRI)-guided localization in the medial prefrontal cortex (mPFC). CCRT includes 6 therapeutic modules and 10 distinct tasks. Both HD-tDCS and CCRT will be administered once daily, 5 days per week, for 4 consecutive weeks, culminating in a total of 20 sessions. Assessments will occur at baseline (T0), after 10 sessions (T1), after 20 sessions (T2), and after 6 months of follow-up (T3). The primary outcome measure is the change in cognition. We will employ multimodal MRI, serum concentrations of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to explore the underlying mechanisms. Expected Results: An involvement of mPFC and synaptic plasticity in response to HD-tDCS and CCRT is hypothesized. Conclusion: The study will provide empirical evidence for the effectiveness of combined therapy at an individual level, explore its mechanisms, and may ultimately result in personalized medicine. Clinical Trial Registration: ChiCTR2500102731, https://www.chictr.org.cn/hvshowprojectEN.html?id=276964&amp;v=1.0.

Background:The objective of this study is to develop an easily applicable scale to measure the course of treatment and the level of recovery for mental problems in various dimensions, which can be used in clinical practice and research.Methods:The validity and reliability test of Moodist Outcome Inventory (MOI) were conducted with 293 participants. Criterion-related validity was investigated by assessment with the Brief Psychiatric Rating Scale (BPRS), Disability Assessment Schedule (WHO-DAS-II), and Psychological Distress Scale (K10-PDS). Factor analysis was investigated by assessment with clinical and non-clinical samples. The sample was followed for six clinical assessments and evaluated by repetitive analysis of Variance (ANOVA) measurement.Results:The Cronbach’s alpha coefficient of the total scale was noted to be 0.89 in the reliability analysis. In the exploratory factor analysis, the single factor explaining 75.64% of the total variance was attained, and all items were included in this factor. Forty cases completed six clinical assessments, and the change between the MOI scores during the time interval was noted to be statistically significant. The correlation of the MOI scale with the K-10, WHO-DAS-II, and BPRS scales was noted to be 0.62, 0.73, and 0.65, respectively. In six consecutive assessments, the mean scores of all scales dropped significantly. The cut-off point of the scale was recorded as 7.27, and the reliable change index (RCI) was noted as 2.5.Conclusion:MOI was assessed as a valid and reliable scale for evaluating the course of treatment. The strengths of the scale are that it assesses both symptoms and well-being, is short, and can be implemented in clinical practice.