Tardive dyskinesia (TD) may reflect an intrinsic neurobiological vulnerability associated with schizophrenia, yet metabolic alterations in the caudate nucleu, a key brain region regulating involuntary movements-remain poorly characterized by proton magnetic resonance spectroscopy (1 H-MRS). We investigated the relationship between caudate nucleus metabolite concentrations and TD symptoms using 1 H-MRS. We recruited 117 patients with schizophrenia, including 67 patients with TD and 50 patients without TD (NT). We also recruited 41 healthy controls (HCs). Absolute metabolite concentrations of N-acetylaspartate plus N-acetyl-aspartyl-glutamate (tNAA), creatine (Cr) and glutamine plus glutamate (Glx) in the caudate nucleus were quantified using a 3.0-T MRI scanner with water signal referencing. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS). Among-group differences were analyzed using analysis of covariance with sex, age and years of education as covariates, followed by Bonferroni correction for multiple comparisons. After correction, the adjusted p-value was 0.017. Regression analysis was performed on metabolic indexes in the TD group with disease duration as a covariate. No significant differences in age, sex, or education level were observed among the groups. Additionally, no significant differences in PANSS scores or antipsychotic medication dosage were observed between the TD and NT groups. The TD group exhibited a significantly longer disease duration than the NT group (p < 0.05). Absolute tNAA levels—a marker of neuronal integrity—were significantly lower in the TD group than in the NT group (p < 0.05), while Cr (involved in energy metabolism) and Glx (involved in excitatory neurotransmission) levels did not significantly differ. These findings suggest reduced neuronal viability in the caudate nucleus in TD, though the clinical implications warrant further investigation.

Major depressive disorder (MDD) exhibits substantial clinical and neurobiological heterogeneity, along with marked variability in treatment response, underscoring the need for objective neuroimaging markers to inform personalized interventions. Twenty-two patients with MDD and twenty-one age- and sex-matched healthy controls (HCs) were enrolled. Depressive symptoms were assessed using the 17-item Hamilton Rating Scale for Depression (HAMD17), and the Hamilton Rating Scale for Anxiety (HAMA), while cognitive function was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Structural magnetic resonance imaging (sMRI) was performed to assess cortical features in MDD patients and HCs. Cortical morphological features [fractal dimension (FD), gyrification index (GI), sulcus depth (SD), and cortical thickness (CT)] were quantified using the automated Computational Anatomy Toolbox (CAT12). Multiple regression analyses were conducted to identify cortical regions in which baseline morphology was associated with subsequent depressive and cognitive changes, controlling for age and sex (voxel-wise p < 0.001, family wise error corrected cluster-level p < 0.05). To further assess the stability and potential out-of-sample consistency of these associations, exploratory leave-one-out cross-validation (LOOCV) analyses with permutation testing were performed. Baseline FD in the left superior frontal cortex (SFC), left cuneus, right rostral middle frontal cortex and right lateral occipital cortex (LOC), GI in the left LOC, and CT in the bilateral insula and pericalcarine cortex were significantly associated with greater improvement in depressive symptoms following antidepressant treatment. In addition, lower baseline SD in the left LOC was associated with greater improvement in delayed memory. Single-ROI models (adjusted for age and sex) revealed that baseline left cuneus FD and left SFC FD was significantly correlated with changes in HAMD17 and HAMA, respectively, and the baseline left LOC/lingual SD showed a moderate cross-validated correlation with delayed memory change. These associations were supported by permutation testing, whereas the model for memory improvement showed only exploratory, non-significant cross-validated performance. Baseline cortical morphometric features were associated with clinical and cognitive changes following antidepressant treatment in MDD. Single-ROI LOOCV models based on left cuneus and left SFC FD showed cross-validated associations with symptom improvement. These findings are preliminary and should be interpreted with caution, pending replication in independent cohorts.

White matter abnormalities are important for understanding schizophrenia and related behaviors. However, the relationship between a history of suicide attempts and alterations in white matter microstructure among individuals with schizophrenia, and its impact on neurocognition, remains unclear. This study scanned 283 individuals diagnosed with schizophrenia and 189 healthy controls. Fractional anisotropy (FA) derived from diffusion tensor imaging is used to assess white matter microstructure. Neurocognitive performance was assessed using the MATRICS Consensus Cognitive Battery. Compared to healthy controls, schizophrenia patients with a history of suicide attempts showed widespread reductions in white matter FA across multiple brain regions (FDR-corrected p < 0.05). In uncorrected analyses, patients with a history of suicide attempts showed a significant lower FA in the external capsule (EC) (p = 0.033, Cohen’s d = -0.26) compared to patients without such history; two-week suicidal ideation was also associated with lower FA in the inferior fronto-occipital fasciculus (p = 0.018, d = -0.29). After FDR correction, none remained significant (all adjusted p > 0.05). A significant interaction was observed between suicide‑attempt history and EC FA in relation to the social cognition T‑score (p for interaction = 0.022). Contrary to prior findings in mood disorders, we did not observe robust white matter microstructural alterations associated with suicide attempts in schizophrenia. EC FA was significantly associated with social cognition performance only in patients without a history of suicide attempts. Schizophrenia patients with suicide attempts show widespread FA reductions versus healthy controls. EC FA is associated with social cognition only in non‑attempters, with a significant interaction by suicide history. No FA differences between attempters and non-attempters survive FDR correction.

While EEG features differentiate Major Depressive Disorder (MDD) from healthy controls (HC), their clinical utility as biomarkers depends on a monotonic trajectory across the disease spectrum, from the acute (AC) phase to the maintenance (MA) phase and finally to the healthy baseline. However, the progression of the MA phase remains poorly understood in traditional marker analysis. Analyzing EEG data from 74 individuals (24 AC, 23 MA, and 27 HC), this study provides a comprehensive evaluation of classic ERP and resting-state indices across AC, MA, and HC groups. Our results demonstrate that almost no conventional metrics strictly satisfy the criterion of monotonic progression, likely due to profound inter-individual heterogeneity. These findings highlight the inherent limitations of group-level feature extraction and provide critical insights for developing future paradigms and algorithms to identify neurobiological markers with genuine clinical utility.

Background Visual perceptual functions are frequently disrupted in patients with schizophrenia. The nature and degree of the visual abnormalities experienced by patients provide important information about altered cognitive mechanisms and may serve as potential endophenotypes for classification and diagnosis of schizophrenia. Methods To characterize dynamic and integrative visual functions and distinguish patients with schizophrenia from healthy controls, we compared performance on six visual tasks between patients and healthy controls. The tasks included binocular rivalry (interocular dynamics), structure from motion (3D-surface dynamics), surround suppression of contrast (contextual modulation), contour integration (form integration), coherent motion (motion integration), and motion speed discrimination (motion sensitivity). The same set of tests was conducted in 61 early-stage outpatients and 69 chronic inpatients and controls, allowing us to see the effects of long-term treatment on patients' visual functions. Results Compared with healthy controls, patients experienced slower switching in binocular rivalry but faster switching in structure from motion, along with impaired spatial form integration. Inpatients had reduced motion sensitivity, while outpatients had deficits in motion integration, two groups differed in susceptibility to surround contrast suppression. Multidimensional test data supported more accurate classification between patients and controls. Conclusions Patients with schizophrenia have specific patterns of visual perceptual abnormalities in dynamic and integrative information processing, with deficit in coherent motion (considered more state-linked) more apparent in early-stage outpatients and poor motion speed discrimination (linked to stable traits) seen in chronic inpatients. There is a significant advantage of using multiple independent tests to assist in the classification and diagnosis of schizophrenia.

OBJECTIVE:Currently, there are few studies on the efficacy and safety of lower dose electroconvulsive therapy (ECT) in adolescents with depressive mood and suicidal ideation. This study aims to investigate a preliminary exploration of lower dose ECT on improving depressive symptoms and suicidal ideation in adolescents with major depressive disorder (MDD), as well as to explore its impact on short-term cognitive function. METHOD:This non-randomized controlled study compared a prospective intervention cohort receiving 8 sessions of low-dose ECT (n = 84) with a historical control cohort (n = 89) from the same institution that received antidepressant medication only. A1:1 propensity-score matching (PSM) approach was used to control for confounding factors between the two groups. RESULTS:Compared to the control group, the ECT group showed significant improvements in the suicidal ideation from the end to 6 weeks after the treatment (p < 0.001) as well as improvements in depressive symptoms (p < 0.001). There was no significant statistical difference in short-term cognitive performance between the lower dose ECT group and the control group; however, the long-term effects of ECT on cognition remain to be elucidated. CONCLUSIONS:This study preliminarily indicates that lower dose ECT may alleviate depressive symptoms and suicidal ideation in adolescents with MDD in the short term, and no serious adverse events were recorded during the treatment. No significant impairment in short-term cognitive function was observed in relation to lower dose ECT, but the long-term effects of ECT on cognitive function remain to be clarified.

Background The co-occurrence of depressive and hypomanic symptoms complicates mood disorder assessment and treatment. However, the symptom pathways linking these domains remain poorly understood. This study examined the network structure of depressive and hypomanic symptoms to identify key bridge symptoms. Methods Cross-sectional data from 6,913 psychiatric outpatients were analyzed using the Beck Depression Inventory-II (BDI-II) and Hypomania Checklist-32 (HCL-32). A Gaussian Graphical Model estimated symptom associations, and bridge centrality indices identified symptoms linking depressive and hypomanic communities. A Network Comparison Test evaluated differences between a Depressive Symptoms (DS) group and a Hypomanic-like Symptoms (HyS) group. Results Two distinct but interconnected symptom communities were identified. Irritability (HCL26), suicidal thoughts (BDI-II9), and impatience (HCL25) showed the highest bridge strength, indicating strong cross-domain connectivity. Social activity (HCL15) and loss of interest (BDI-II12) had the highest bridge betweenness, suggesting important roles in linking behavioral activation and depressive symptoms. Although overall network structure did not differ significantly between groups, the DS group showed higher global strength, indicating stronger overall symptom interdependence. Conclusions Irritability, social over-activation, and related symptoms occupy central positions connecting depressive and hypomanic symptom communities. These bridge symptoms may represent transdiagnostic indicators of affective symptom connectivity and provide potential directions for future longitudinal studies examining symptom evolution and clinical relevance.

BACKGROUND:While smoking and drinking are known to influence cognitive function, the future risk of incident dementia among individuals diagnosed with mental and behavioral disorders due to tobacco use (MBT) and mental and behavioral disorders due to alcohol use (MBA) remains unclear. METHODS:Data were sourced from the UK Biobank, a publicly accessible database in the United Kingdom. The analysis included 362,934 participants free of dementia at baseline. MBT and MBA were identified using ICD-10 codes from first occurrence data in the UK Biobank dataset. Dementia outcomes, defined algorithmically by the UK Biobank, included all-cause dementia, Alzheimer's disease, and vascular dementia. Cox regression models assessed the associations of MBT and MBA with incident dementia. RESULTS:Among only smoking participants, those with MBT had an adjusted hazard ratio (HR) of 1.47 (95% confidence interval [CI]: 1.10-1.96) for all-cause dementia, compared with non-MBT participants. Among only drinking participants, those with MBA had an adjusted HR of 2.34 (95% CI: 2.05-2.68) for all-cause dementia, compared with non-MBA participants. Among both smoking and drinking participants, those with both MBT and MBA (HR = 3.86, 95% CI: 2.78-5.35), those with only MBT (HR = 1.31, 95% CI: 1.02-1.67), and those with only MBA (HR = 2.46, 1.39-4.35) had a significantly higher risk of incident dementia, compared with non-MBT and non-MBA participants. CONCLUSIONS:Individuals diagnosed with MBT, MBA, or both are associated with a higher likelihood of incident dementia. These findings underscore the need for interventions targeting these behaviors to mitigate the dementia incidence.

OBJECTIVES:P2RX7 has been implicated in bipolar disorder, major depressive disorder, schizophrenia, anxiety disorders, Alzheimer's disease, and Parkinson's disease. However, the specificity and comparability of these associations remain unclear. This study aimed to systematically evaluate multiple neuropsychiatric disorders to identify those most robustly associated with P2RX7. METHODS:We analyzed 1861 imputed SNPs spanning the P2RX7 gene in 1,087,925 individuals from 72 independent cohorts across 18 neuropsychiatric disorders. SNP-disease associations were assessed within each cohort, followed by meta-analysis and false discovery rate (FDR) correction to identify significant disease-risk variants. P2RX7 mRNA and protein expression across tissues or cells was characterized. Functional analyses evaluated the regulatory effects of disease-associated SNPs on P2RX7 mRNA expression, subcortical gray matter volumes (GMVs), cortical surface area (SA), and cortical thickness (TH). RESULTS:Bipolar disorder showed the strongest association with P2RX7 variants in European Americans (EAs) (4.0 × 10-8 ≤ p ≤ 0.004; 3.8 × 10-5 ≤ q ≤ 0.05), followed by schizophrenia in EAs (8.9 × 10-6 ≤ p ≤ 2.6 × 10-4; 9.4 × 10-3 ≤ q ≤ 0.043) and Chinese populations (2.1 × 10-5 ≤ p ≤ 1.7 × 10-3; 6.8 × 10-3 ≤ q ≤ 0.049), and major depression in both EAs (p = 4.1 × 10-5; q = 0.030) and Chinese (4.3 × 10-5 ≤ p ≤ 0.009; 6.1 × 10-3 ≤ q ≤ 0.046). The significance of most associations and their relative ranking across disorders was maintained in the trans-ancestry meta-analysis. Expression analysis revealed that P2RX7 mRNA and protein expression were abundant in the brain, glial cells and macrophages. Approximately half of the disease-associated SNPs significantly influenced P2RX7 mRNA expression in nine brain regions (1.0 × 10-7 ≤ p ≤ 0.047) and altered GMV, SA, and TH of seven brain regions (1.9 × 10-4 ≤ p ≤ 3.4 × 10-3). CONCLUSION:P2RX7 is most consistently and specifically associated with bipolar disorder, schizophrenia, and major depression, supported by both statistical and biological evidence.

Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory and cognitive decline. Recent studies highlight the significant role of microRNAs (miRNAs) in regulating genes related to AD. This research aims to develop miRNA-associated gene regulatory networks as candidate AD biomarkers.Methods We recruited 85 AD patients and 74 healthy controls, conducting whole blood miRNA sequencing and applying machine learning to identify differentially expressed miRNAs, which were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We used bioinformatics databases to predict target genes for these miRNAs and obtained gene expression data from the Gene Expression Omnibus (GEO) database (GSE122063 and GSE18309). Using the ggplot2 package in R, we discovered the overlap between miRNA target genes and differentially expressed genes (DEGs) from the GSE datasets. Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the DEGs were then conducted using the Metascape database. Key hub genes were pinpointed by constructing a protein-protein interaction (PPI) network with the Retrieval of Interacting Genes (STRING) database and analyzing it with cytoHubba. Drug-gene interactions were predicted and examined using the Drug-Gene Interaction database (DGIdb) (http://www.dgidb.org/).Results qRT-PCR was used to confirm the expression of the hub genes. The results showed that four miRNAs (miR-192-5p, miR-484, miR-21-5p, and miR-24-2-5p) were downregulated, while two target RNAs (SLC32A1 and GAD1) were upregulated.Discussion This regulatory network, which is strongly linked to AD, has been initially identified as a candidate biomarker for AD. Our research provides new insights into the pathogenic mechanisms of AD, potentially improving the understanding of miRNAs' role in the disease.

Background: Nonsuicidal self-injuries (NSSIs) are an important contributing factor to adolescent suicide, and various shared factors influence the risk of both NSSIs and suicide attempts (SAs). Both are important predictors of suicide and are part of a continuum of suicidal behaviors. Further exploration of the relationship between adolescent NSSI and SA may facilitate suicide prevention efforts. Methods: An online survey was conducted among 9,140 participants. Network analysis methods were used to explore expected influence (EI), bridge expected influence (BEI), edge weights, and differences between adolescents that have and have not attempted suicide (NSSI-SA and NSSI-NoSA, respectively). Results: Of the 9,140 participants, 7,030 completed the questionnaire, yielding a participation rate of 76.91%. Participants with at least one NSSI were retained, with 2,496 (35.50%) included in the network analysis. The strongest EI node for both networks was “emotion regulation strategies” (E = 1.389 and 1.393), and that for BEI was “personal distress” (Interpersonal Reactivity Index—personal distress; E = 0.497 and 0.492). Network comparisons revealed significant differences in NSSI 4 (“intentionally hitting walls, tables, and other hard objects”; E(Δ) = −0.384, P < 0.001), significant differences in BEI with regard to “perspective taking” (Interpersonal Reactivity Index—perspective taking; E(Δ) = −0.215, P < 0.001), and significant differences in edge weights between NSSI 4 and NSSI 5 (“intentionally hurting oneself by hitting with a fist, palm, or hard object”; E(Δr) = −0.173, P < 0.001). Conclusions: Our study suggests that interventions in the form of emotion regulation strategies can alleviate symptoms throughout the entire network. Attention should be paid to instances when NSSI 4 and NSSI 5 behaviors co-occur frequently.

Evidence on betahistine for cognitive impairment in schizophrenia is limited. This study evaluated its feasibility, safety, and preliminary efficacy to lay the groundwork for future randomized controlled trials. Thirty-one inpatients with schizophrenia, aged 18-60 years, undergoing treatment with olanzapine received betahistine (16 mg, three times daily) for 12 weeks. Cognitive function, clinical symptoms, and side effects were assessed at baseline and again at 12 weeks postintervention. After 12 weeks of betahistine treatment, patients with schizophrenia showed a significant increase in the total Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery score (p < .01). Increases were observed across multiple cognitive domains, including speed of processing, attention, working memory, verbal and visual learning, and reasoning and problem solving. Reductions in Positive and Negative Syndrome Scale scores were also observed, particularly for negative symptoms and total score (p < .05). Linear regression analysis revealed a significant negative correlation between age and cognitive scores (β = -0.37, p < .05). No adverse effects were reported. In this 12-week, single-arm study, adjunctive betahistine treatment was associated with observed improvements in cognitive performance and reductions in clinical symptom scores during the treatment period in patients with schizophrenia receiving olanzapine. Furthermore, advancing age is a key factor contributing to cognitive decline in the studied population. Betahistine was well-tolerated. This study explores betahistine as an adjunctive treatment for cognitive impairment in schizophrenia, with potential implications for improving cognitive outcomes and informing future treatment strategies. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Abstract Background Treatment-resistant schizophrenia (TRS) is characterized by severe cognitive impairments. However, the underlying mechanisms driving these deficits and strategies to mitigate them remain unclear. Elevated homocysteine levels have also been implicated in disease progression. We aimed to explore the relationship among serum homocysteine levels, working memory, and cortical thickness in patients with TRS. Methods Eighty-five patients with schizophrenia (42 with TRS and 43 with non-TRS [NTRS]) and 58 healthy controls (HCs) were recruited. Serum homocysteine levels were measured using enzymatic cycling. Cortical thickness was assessed using FreeSurfer version 5.3. Mediation analysis was further performed to preliminarily explore the potential interplay among serum homocysteine levels, regional cortical thickness, and working memory performance. Given that the bivariate correlations between homocysteine levels and cortical thickness did not retain significance after false discovery rate (FDR) correction and the cross-sectional design, this analysis aimed to identify potential mediating or suppressive pathways for hypothesis-generating purposes, rather than verifying definite compensatory mechanisms. Results Working memory was significantly impaired in patients with TRS and NTRS compared with HCs. Homocysteine levels were elevated in patients with schizophrenia, particularly in the TRS group. Among individuals with TRS, an inverse relationship was observed between serum homocysteine concentration and working memory ( r = − 0.411, p FDR = 0.02). Our exploratory suppression analyses revealed preliminary statistical links between elevated cortical thickness in the left precentral, postcentral, and precuneus gyri and homocysteine-associated working memory deficits in patients with TRS. These hypothesis-generating observations are constrained by non-significant FDR-corrected correlations and cross-sectional design. Conclusions Our exploratory findings preliminarily indicate that greater cortical thickness within left-hemispheric brain regions may show statistical links to homocysteine-associated working memory deficits in patients with TRS, rather than definitive evidence of partial compensatory mechanisms. Notably, given the cross-sectional study design and non-significant bivariate correlations observed between homocysteine levels and cortical thickness following FDR correction, these results are strictly hypothesis-generating and cannot support causal inferences. The mediation-suppression analysis, performed despite non-significant FDR-adjusted pairwise associations, offers tentative clues regarding potential neural correlation patterns. Further longitudinal or interventional studies are required to validate these preliminary observations.

BackgroundHippocampal neurogenesis shapes adaptation and improves responses to stress. Patients with schizophrenia show marked functional impairment and abnormal stress sensitivity. However, it remains unclear how structural abnormalities in specific hippocampal subregions are related to altered perceived stress and clinical symptoms in schizophrenia.MethodsWe recruited 97 first-episode patients with schizophrenia (FEPS) and 47 healthy controls (HC). Perceived stress and psychopathology were assessed using the Perceived Stress Scale (PSS) and the Positive and Negative Syndrome Scale (PANSS), respectively. Structural MRI was acquired on a 3.0-T scanner, and hippocampal subregions were segmented using validated, standardized protocols. Left and right subregional volumes were summed to obtain calculate bilateral volumes.ResultsCompared to HC, the FEPS group showed higher perceived stress, reduced fimbria volumes, and increased hippocampal tail volumes after adjustment for intracranial volume, age, sex, and education. In HC, several hippocampal subregion volumes were positively correlated with stress perception; however, these associations were absent or disrupted in FEPS. In FEPS, stress perception was positively associated with positive and anxiety/depression symptoms. Additionally, specific hippocampal subfield volume was positively associated with negative symptoms.ConclusionsFEPS was characterized by aberrant perceived stress, altered hippocampal subregional volumes, and disrupted links between stress perception and hippocampal structure. The interrelations among stress, clinical symptoms, and hippocampal subfields suggest altered psychological and neurobiological processes underlying stress regulation processes in FEPS.

The Symptom Checklist-90 (SCL-90) is widely used in Chinese adolescents, but its practical utility is limited by its length and by structural problems in the traditional ten-factor model. To address these issues, this study developed and validated a brief computerized adaptive testing (CAT) system based on a theoretically informed six-factor model. Using a clinical sample of 10,052 adolescent outpatients, confirmatory factor analysis showed the traditional ten-factor model had a substantial identification problem: a non-positive definite matrix from extremely high factor correlations. In contrast, the proposed six-factor model had acceptable fit (CFI = 0.875, RMSEA = 0.061). The CAT system was developed via multidimensional item response theory. In post hoc simulations with a stopping rule (SE < 0.4), average test length was reduced from 90 to 37 items (58.9% reduction), maintaining high agreement with full-scale estimates (≥ 0.89) and acceptable marginal reliability (≥ 0.76). External validation with the SDS, SAS, and Y-BOCS provided preliminary support for external validity. Overall, this study supports a clinically meaningful six-factor representation of the SCL-90 and provides an efficient adaptive assessment framework for Chinese adolescents in clinical settings.

BACKGROUND:Major depressive disorder (MDD) in adolescence is a major public health issue, with childhood emotional neglect recognized as a key environmental risk factor. However, the neurobiological mechanisms linking early emotional neglect to brain development and depression remain unclear. Previous studies have largely focused on single-modal imaging, neglecting the potential benefits of integrating structural and functional data. METHODS:34 adolescents with MDD and 30 healthy controls (HCs) participated in the study. The key brain area was identified by calculating and comparing the intensity of structure-function coupling (SFC) between the two groups. Mediation analysis and whole-brain functional connectivity analysis were subsequently employed to explore the relationship between this brain region, emotional neglect, and clinical depression symptoms. RESULTS:Adolescents with MDD exhibited significantly lower SFC in the left frontal operculum (L-FOP) compared to HCs (p < 0.001). Mediation analysis across all three models consistently revealed that the SFC of L-FOP plays a crucial role in linking emotional neglect to depression (p < 0.05). Additionally, extensive disruptions in functional connectivity between the L-FOP and key brain networks were observed, with these altered connections strongly correlating with clinical depressive symptoms (p < 0.05). CONCLUSION:Childhood emotional neglect may increase vulnerability to adolescent depression by disrupting SFC within the L-FOP, a critical hub for sensory, emotional, and cognitive integration. This decoupling is associated with widespread brain network dysfunction, contributing to emotional dysregulation and cognitive impairment. These findings highlight the L-FOP as a potential target for early detection and neuromodulation interventions in adolescent depression.

BACKGROUND AND OBJECTIVE:Accurate detection of schizophrenia poses a grand challenge as a complex and heterogeneous mental disorder. Current diagnostic criteria rely primarily on clinical symptoms, which may not fully capture individual differences and the heterogeneity of the disorder. In this study, a discriminative model of schizophrenic speech based on deep learning is developed, which combines different emotional stimuli and features. METHODS:A total of 156 schizophrenia patients and 74 healthy controls participated in the study, reading three fixed texts with varying emotional stimuli. The log-Mel spectrogram and Mel-frequency cepstral coefficients (MFCCs) were extracted using the librosa-0.9.2 toolkit. Convolutional neural networks were applied to analyze the log-Mel spectrogram. The effects of different emotional stimuli and the fusion of demographic information and MFCCs on schizophrenia detection were examined. RESULTS:The discriminant analysis results showed superior performance for neutral emotional stimuli compared to positive and negative stimuli. Integrating different emotional stimuli and fusing features with personal information improved sensitivity and specificity. The best discriminant model achieved an accuracy of 91.7%, sensitivity of 94.9%, specificity of 85.1%, and ROC-AUC of 0.963. CONCLUSIONS:Speech analysis under neutral emotional stimulation demonstrated greater differences between schizophrenia patients and healthy controls, enhancing discriminative analysis of schizophrenia. Integrating different emotions, demographic information and MFCCs improved the accuracy of schizophrenia detection. This study provides a methodological foundation for constructing a personalized speech detection model for schizophrenia.

Objective: Cognitive impairment occurs throughout the entire course of and affects the work and life of patients with major depressive disorder (MDD). The gut microbiota, kynurenine pathway (KP) and inflammatory response may have important roles in the mechanism of cognitive impairment in MDD patients. Consequently, our goal was to investigate the association among the gut microbiota, inflammation, KP, and cognition in MDD. Method: We enrolled patients with MDD (N = 86) and healthy controls (HCs, N =120) in this research. The study involved participant data regarding the levels of serum inflammatory factors (interleukin [IL]-1 beta, IL-4, IL-6, brain-derived neurotropic factor [BNDF], migration inhibitory factor [MIF], tumor necrosis factor [TNF]-alpha, vascular endothelial growth factor [VEGF]), gut microbiota and cognitive function (MCCB) were collected. Results: Patients demonstrated poorer cognitive function. Gut microbiota, such as Bacteroide, Prevotella, Faecalibacterium and Parabacteroides between MDDs and HCs were significantly different. Moreover, in patients with MDD, we found that different microbiomes were related to cognition and that Acidaminococcus was positively correlated with multiple domains of cognition. Allisonella and Acidaminococcus were significantly positively correlated with BDNF and negatively correlated with MIF. Alloprevotella, Blautia, and Megamonas were positively correlated with kynurenine/tryptophan (KYN/TRP). Acidaminococcus was negatively correlated with 3-hydroxykynurenine (3-HK). BDNF levels was significantly positive correlated with kynurenic acid (KA) and quinolinic acid (QA). Conclusion: The results of the present study suggest that the gut microbiota is associated with cognitive function, cytokine levels and KP metabolism in patients with MDD; however, the mechanism of the interaction between cognition and gut microbiota in MDD patients require further investigation.

Previous research suggests that individuals with schizophrenia may exhibit impairments in sensory attenuation. This neurocognitive process is defined as reduced neural responses in sensory cortices to self-generated actions compared with externally triggered sensory inputs. However, the specific neuroimaging association between sensory attenuation deficits and schizophrenia has not been fully established. To elucidate the neuroimaging signatures of these impairments, the present study employed a modified action-outcome contingent paradigm combined with a task-based functional magnetic resonance imaging in 20 individuals with schizophrenia and 21 matched healthy controls. Participants completed voluntary (active) and experimenter-administered (passive) button-press tasks respectively, both eliciting auditory feedback, to isolate the neural correlates of sensory attenuation. Neuroimaging analysis revealed characteristic abnormalities in neural activity within the left middle temporal gyrus/superior temporal gyrus of patients. First, compared to the healthy controls, absence of activation attenuation (passive-active) was observed in these regions under active conditions. This phenomenon suggests a specific impairment in the ability to discriminate self-generated stimuli. Second, when identical auditory stimuli were passively received, significantly lower baseline activation levels within these regions were found in patients than in healthy controls. This task-specific characteristic highlights impaired detection and evaluation of environmentally driven stimuli in patients.

BackgroundObesity and dysregulated cytokine levels are prevalent in schizophrenia patients undergoing antipsychotic treatment. While cytokines are implicated in obesity, their relationship with psychopathology in schizophrenia remains underexplored. This study investigated associations between body mass index (BMI), cytokine levels, and clinical symptoms in chronic schizophrenia patients.MethodsIn this cross-sectional study,201chronic schizophrenia patients (Chinese Han population) were stratified into high BMI (BMI≥25kg/m2) and low BMI (BMI<25kg/m2) groups. Psychopathology was assessed using the Positive and negative Syndrome Scale (PANSS). Serum cytokine (IL-2, IL-6, TNF-α) and metabolic parameters were measured in 69 participants.ResultsA significant negative correlation was observed between BMI and IL-2(p=0.013). TNF-α levels inversely correlated with PANSS total (p=0.010) and general psychopathology scores(p=0.042). The high BMI group exhibited lower PANSS negative subscores and elevated glucose, triglycerides (TG) and apolipoprotein B (ApoB) compared to the low BMI group(all p<0.05). Multivariate regression identified IL-2 as an independent factor associated with lower BMI, while TNF-α independently contributed to general psychopathology.ConclusionsHigher BMI in chronic schizophrenia is associated with reduced IL-2 levels, attenuated negative symptoms, and adverse lipid profiles. TNF-α may modulate psychopathology severity. These findings highlight complex interactions between metabolic dysregulation, immune markers, and clinical manifestations in schizophrenia.