Evidence has shown that ibuprofen and celecoxib are effective in improving depressive symptoms, but their mechanisms of action are unclear. In this study, we aimed to determine the relationship between these two drugs and depressive disorder (DD) and elucidate potential mechanisms of action.

Relevant targets for ibuprofen, celecoxib, and DD were obtained and screened from multiple online drug and disease public databases. A protein-protein interaction network was obtained. The Centiscape and CytoHubba plug-ins were applied to screen for core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking was performed to predict the binding of ibuprofen and celecoxib to core targets. Examined the differences in core target protein expression between DD patients (DDs, n = 18) and healthy controls (HCs, n = 16) as a further experimental validation of the network pharmacology results.

In total, 220 potential targets for ibuprofen and 316 potential targets for celecoxib were identified and associated with DD. The antidepressant effects of both drugs involve many key targets in pathways such as "pathways in cancer" and "neuroactive ligand-receptor interaction," including ALB, BCL2, MAPK3, SRC, STAT3, EGFR, and PPARG. The binding affinity of ALB with ibuprofen is the strongest, and it is connected only by hydrophobic interactions. Celecoxib exhibits higher affinity at multiple targets such as SRC, EGFR, and PPARG, with stronger and more specific intermolecular interactions, including salt bridges and halogen bonds. Clinical trials have found that serum ALB expression in DDs is significantly lower than that in HCs (t = 6.653, p < 0.001), further confirming the potential role of ibuprofen in DD.

Ibuprofen and celecoxib primarily exert their antidepressant effects through targets and pathways related to inflammation, neural signaling, and cancer, with celecoxib showing a stronger potential antidepressant effect. The expression difference of the core target ALB between depression and healthy individuals further supports the potential effect of the drug on DD. Our findings propose new treatment strategies, support the link between inflammation and depression, and encourage reassessing existing medications for depression.

Plasma proteins play critical roles in a series of biological processes and represent a major source of translational biomarkers and drug targets. In this study, we performed Mendelian randomization (MR) to explore potential causal associations of protein quantitative trait loci (pQTL, n = 54,219) with major depressive disorder (MDD) using summary statistics from the PGC (n = 143,265) and further replicated in FinnGen cohort (n = 406,986). Subsequently, gene expression quantitative trait loci (eQTL) of identified proteins were leveraged to validate the primary findings in both PGC and FinnGen cohorts. We implemented reverse causality detection using bidirectional MR analysis, Steiger test, Bayesian co-localization and phenotype scanning to further strengthen the MR findings. In primary analyses, MR analysis revealed 2 plasma protein significantly associated with MDD risk at Bonferroni correction (P < 3.720 × 10-5), including butyrophilin subfamily 2 member A1 (BTN2A1, OR = 0.860; 95 % CI, 0.825-0.895; P = 1.79 × 10-5) and butyrophilin subfamily 3 member A2 (BTN3A2, OR = 1.071; 95 % CI, 1.056-1.086; P = 3.89 × 10-6). Both the identified proteins had no reverse causality. Bayesian co-localization indicated that BTN2A1 (coloc.abf-PPH4 = 0.620) and BTN3A2 (coloc.abf-PPH4 = 0.872) exhibited a shared variant with MDD, a finding that was subsequently validated by HEIDI test. In the replication stage, BTN2A1 and BTN3A2 were successfully validated in the FinnGen cohort. This study genetically determined BTN2A1 and BTN3A2 were associated with MDD and these findings may have clinical implications for MDD prevention.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by multiple dysfunctions in behavior, the nervous system, and the immune system. Increasing evidence suggests that mitochondrial DNA (mtDNA) plays a crucial role in the pathology of ASD. In clinical practice, altered mtDNA levels have been observed in various tissues of individuals with ASD. Mutation or oxidation of mtDNA is also closely related to the immune response associated with the pathology of autism. With mtDNA identified as a causal factor, much interest has focused on how its production affects neurodevelopment and neurophysiology. Here, we review how mtDNA leads to dysfunction of cellular mitochondria and immune response. We also illustrate the relationship between mtDNA alterations and the pathology of autism. Finally, we discuss the existing evidence on cell-free mtDNA associated with ASD and look forward to its application in clinical diagnosis and treatment.

Chronic pain conditions frequently coexist and share common genetic vulnerabilities. Despite evidence showing associations between pain and depression, the additive effect of co-occurring pain conditions on depression risk and the underlying mechanisms remain unclear. Leveraging data from 431,038 UK Biobank participants with 14-year follow-up, we found a significantly increased risk of depression incidence in individuals reporting pain, irrespective of body site or duration (acute or chronic), compared with pain-free individuals. The depression risk increased with the number of co-occurring pain sites. Mendelian randomization supported potential causal inference. We constructed a composite pain score by combining individual effects of acute or chronic pain conditions across eight body sites in a weighted manner. We found that depression risks increased monotonically in parallel with composite pain scores. Moreover, some inflammatory markers, including C-reactive protein, partially mediated the association between composite pain scores and depression risk. Considering the high prevalence of comorbid depression and pain, pain screening may help identify high-risk individuals for depression.

rTMS has shown some effect in improving cognitive functions in patients with schizophrenia. However, these findings were controversial, and specific mechanisms of action and optimal therapeutic parameters still require further investigation. This study aimed to examine predictive biomarkers of the efficacy of rTMS in cognitive improvement in schizophrenia. A secondary analysis of a previous randomized, controlled trial was performed. Fifty-six patients were allocated to the active rTMS and 28 to the sham group. Patients received 6 weeks of treatment and were followed up for 18 weeks. Cognition was assessed and blood biomarkers were measured in all patients. In patients with schizophrenia, there was a significant interaction between time and group on immediate memory. Furthermore, this study found that after controlling for confounders, patients with higher baseline white blood cell (WBC) counts showed less improvement in immediate memory after rTMS than patients with lower WBC counts. Linear regression analysis showed that WBC counts were associated with immediate memory improvement after rTMS treatment. Our results reveal that WBC counts at baseline correlated with the response to rTMS in patients with schizophrenia. Patients with higher baseline WBC counts improved less after rTMS intervention than those with lower WBC counts.

Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations.

We evaluated whether higher plasma interleukin 6 (IL-6) levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing early (BeneMin [Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism], n = 201, 72.8% male) and established (iRELATE [Immune Response & Social Cognition in Schizophrenia], n = 94, 67.3% male) schizophrenia cohorts. Using structural equation modeling in a subsample (iRELATE: n = 42, 69.0% male; BeneMin: n = 102, 76.5% male) with data on structural brain metrics (cortical thickness and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in early and established schizophrenia samples combined and in early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose.

Higher plasma IL-6 levels were related to more severe depressive symptoms in early schizophrenia (p < .05) and negative symptoms in established schizophrenia (p < .05). Structural equation modeling findings in early and established schizophrenia samples combined and early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (p > .05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (p < .05).

Our results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes.

Pineal cysts are benign, nonneoplastic lesions of the pineal gland, often identified incidentally on MRI scans. Although these cysts are usually asymptomatic, they can occasionally enlarge and compress adjacent structures, leading to neurological complications such as obstructive hydrocephalus and Parinaud's syndrome. The underlying mechanisms of pineal cyst development remain largely unclear, although inflammation - common in rheumatological conditions such as fibromyalgia - and mechanical stress have been suggested as contributing factors. In addition, the incomplete blood-brain barrier of the pineal gland raises the possibility that chronic lithium therapy, commonly used for psychiatric disorders and also known for its hyperplastic effects, could facilitate cysts formation through lithium accumulation and epithelial stimulation. We report the case of a 49-year-old woman with bipolar disorder on long-term lithium treatment who presented with a pineal cyst and clinical symptoms consistent with fibromyalgia. A review of the literature highlights possible links between pineal cyst formation, systemic inflammation associated with rheumatological disorders and prolonged lithium exposure. Although the hyperplastic properties of lithium in glandular tissue are well documented, there is no conclusive evidence directly linking lithium use to the development of pineal cysts in humans. The possibility of cystic growth driven by the pro-inflammatory environment of fibromyalgia remains plausible and warrants further investigation of the complex interactions between lithium therapy, systemic inflammation and pineal cystogenesis, particularly in patients with coexisting rheumatological and psychiatric disorders.

More and more evidence shows that infection and immune abnormality are closely related to the increased severity of schizophrenia symptoms. This study aimed to explore the correlation between inflammatory cell counts, sleep quality, and psychiatric symptoms in first-episode schizophrenia patients.

A total of 103 first-episode schizophrenia patients (patient group) admitted to the Anhui Provincial Mental Health Center from November 2021 to August 2022 were included in the study, while 57 healthy individuals (control group) who met the criteria were recruited as the study subjects. The Positive and Negative Symptom Scale (PANSS) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the mental symptoms and sleep status of the patients. Blood analysis results were used to determine the peripheral blood white blood cells (WBC) and lymphocytes of the two groups. Count neutrophils, monocytes, and platelets (PLT) of the two groups. The neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) were calculated. Differential, correlation, and regression analysis were performed on survey data using SPSS 26.0.

Results showed WBC, neutrophils, monocytes, NLR, MLR higher in case vs control group (p<0.05). Correlation analysis found monocytes negatively correlated with sleep time (rs=-0.205, p=0.037) and MLR with arousal factor (rs=-0.204, p=0.039). Linear regression showed that MLR positively affected arousal score (B=7.196, t=2.781, p=0.006) and monocytes negatively affected sleep time score (B=-0.851, t=-2.157, p=0.033). ROC analysis revealed high sensitivity and specificity of WBC, neutrophils, monocytes, NLR, MLR for SCZ symptom prediction.

The study concluded that elevated WBC, neutrophils, monocytes, NLR, and MLR levels in the case group were significantly associated with increased severity of schizophrenia symptoms, particularly affecting sleep and arousal factors, and demonstrated high predictive validity for SCZ symptoms.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Emerging evidence suggests a link between immune dysregulation and ASD. This study investigates alterations in monocyte subpopulations and cytokine production in children with ASD and their potential associations with ASD risk and severity.

Initially, the immune status of peripheral blood mononuclear cells was assessed in cohort-I of 96 typically developing (TD) children and 92 children diagnosed with ASD using flow cytometry. Subsequently, the secretion of cytokines IL-6 and IL-10 by monocytes was evaluated following stimulation with a leukocyte activation mixture and intracellular protein staining technique in cohort-II.

Children with ASD exhibited significantly higher levels of total monocytes, classical monocytes (CD14hi/CD16-), and non-classical monocytes (CD14low/CD16+) compared to TD children (p < 0.001). Elevated levels of classical monocytes (β: 0.395; 95 %CI: 0.260-0.530; p < 0.001) and non-classical monocytes (β: 0.629; 95 %CI: 0.516-0.742; p < 0.001) were significantly associated with ASD after adjusting for age, sex and body mass index. Furthermore, increased production of IL-6 by monocytes was observed in children with ASD (p = 0.001). Logistic regression analysis revealed that classical monocytes (OR: 1.104; 95 %CI: 1.062-1.147; p < 0.001), non-classical monocytes (OR: 2.913; 95 %CI: 2.130-3.986; p < 0.001) and IL-6 production by monocytes (OR: 1.306; 95 %CI: 1.096-1.557; p = 0.003) are risk factors for ASD. Spearman correlation analysis revealed a negative correlation between classical monocyte levels and adaptive behavior developmental quotient (DQ) (r = - 0.377; p = 0.001), fine motor DQ (r = - 0.329; p = 0.003) and personal-social DQ (r = - 0.247; p = 0.029) in children with ASD.

Elevated classical and non-classical monocytes are potential risk factors for ASD and may influence neurodevelopmental outcomes. Further research is needed to elucidate the precise mechanisms and therapeutic implications.

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.

Bipolar disorder (BD) and schizophrenia (SCZ) are uniquely human disorders with a complex pathophysiology which involves adverse neuropathological events in brain development. High disease polygenicity and limited access to live human brain tissue make these disorders exceedingly challenging to study mechanistically. Cellular cultures and brain organoids generated from human-derived pluripotent stem cells preserve the genetic background of the donor cells and recapitulate some of the defining characteristics of human brain architecture and early spatiotemporal development. These model systems have already proven successful in deciphering some of the neuropathological perturbations in BD and SCZ, and methodological advancements, such as the functional integration of two or more region-specific organoids and organoid transplantation in animals, promise to deliver increasingly refined insights. Here we review a selection of recent discoveries achieved by stem cell-based models, with a particular focus on patterns of cellular and molecular convergence and divergence between BD and SCZ. We first provide a brief overview of the evidence from glial and neuronal cell cultures and brain organoids, centering our discussion on several key functional domains, including neuroinflammation, neuronal excitability, and mitochondrial function. We then review recent findings demonstrating the power of integrating stem cell-based systems with gene editing technologies to elucidate the functional consequences of risk variants identified through genetic association studies. We end with a discussion of current challenges and some promising avenues for future research.

Schizophrenia (SZ), a chronic and widespread brain disorder, presents with complex etiology and pathogenesis that remain inadequately understood. Despite the absence of a universally recognized endophenotype, peripheral blood mononuclear cells (PBMCs) serve as a robust model for investigating intracellular alterations linked to SZ.

To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.

PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes (DEGs) and differentially expressed proteins while mapping putative disease-associated signaling pathways. Key findings were validated using western blot (WB) and real-time fluorescence quantitative PCR (RT-qPCR). RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro, with subsequent verification of target gene expression via RT-qPCR. The levels of neuronal conduction proteins, including calmodulin-dependent protein kinase II (caMKII), CREB, and BDNF, were assessed through WB. Apoptosis was quantified by flow cytometry, while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.

The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes, among which 25 DEGs were significantly altered between the SZ group and healthy controls. Notably, haptoglobin (HP), lactotransferrin (LTF), and SERPING1 exhibited marked upregulation. KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis. Clinical sample validation demonstrated elevated protein and mRNA levels of HP, LTF, and SERPING1 in the SZ group compared to controls. WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1. In hippocampal CA1 neurons transfected with lentivirus, reduced SERPING1 expression was accompanied by increased levels of CaMKII, CREB, and BDNF, enhanced cell viability, and reduced apoptosis.

SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.

Although schizophrenia is a severe mental disorder that significantly impacts patients and society, there are currently no reliable blood-based biomarkers to assist in its diagnosis. The diagnosis primarily relies on clinical assessment and patient history, a method that is inherently subjective and prone to errors, potentially leading to diagnostic delays. In this study, we aim to utilize bioinformatics approaches to explore potential blood-based biomarkers for the diagnosis of schizophrenia. By employing advanced bioinformatics techniques, we hope to identify key genes and construct an effective diagnostic model, providing the clinic with a more objective and accurate diagnostic tool.

In this research, we employed bioinformatics techniques to identify potential blood-based biomarkers for the diagnosis of schizophrenia. Initially, we selected schizophrenia-associated differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) database through the datasets GSE27383, GSE38484, and GSE38481. Subsequently, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on these DEGs to elucidate their biological functions and related pathways. Furthermore, we constructed a protein-protein interaction (PPI) network of the differentially expressed genes to identify key genes and matched them with their target microRNAs (miRNAs). In addition, we assessed the diagnostic potential of these key genes through immune infiltration analysis. The aim of this study is to reveal the roles of these hub genes in the pathogenesis of schizophrenia.

Through bioinformatics analysis, we have identified three potential hub genes associated with the pathogenesis of schizophrenia: CTSS, DOK2, and ENTPD1. These genes are significantly correlated with the development of schizophrenia and may serve as promising diagnostic biomarkers for the condition.

In this study, we have identified three pivotal genes-CTSS, DOK2, and ENTPD1-that are intimately associated with the pathogenesis of schizophrenia. The discovery of these genes not only enhances the precision of diagnostic efforts for schizophrenia but also provides a robust scientific foundation for the development of innovative treatment approaches for schizophrenia and related disorders. The identification of these biomarkers offers a tangible basis for early, accurate diagnosis, treatment, prognostic assessment, and rehabilitation evaluation in schizophrenia, potentially improving patients' quality of life and supporting the development of personalized therapeutics and antipsychotic medications.

Schizophrenia is a chronic mental disorder and one of the main causes of disability in the world. Approximately 1% of the general population suffers from this disorder, and almost 30% of cases are unresponsive to antipsychotic therapies. Clozapine is a Food and Drug Administration (FDA)-approved antipsychotic drug for treatment-resistant schizophrenia (TRS). Clozapine is also approved for the prevention of suicide associated with schizophrenia. However, clozapine is not the preferred first-line medication because of its potential AEs, including agranulocytosis, metabolic syndromes, and myocarditis. Clozapine prescription requires weekly absolute neutrophil count (ANC) monitoring for the first six months, followed by biweekly monitoring until the patient has finished one year of treatment. Several psychiatric disorders have been reported to be associated with inflammatory biomarkers. Dysregulation of the immune system and the elevation of pro-inflammatory cytokines were also reported to be associated with schizophrenia, highlighting the necessity of further research into the etiology of the disease and the relationship between the immune system and clozapine-responsiveness to support better management of symptoms and potential AEs. In this framework, we searched PubMed using the medical subject headings (MeSH) terms "clozapine", "antipsychotics", "schizophrenia", "treatment-resistant schizophrenia", "immune system", "inflammation", "neuroinflammation", "biomarker", "cytokine", and "chemokine" with the aim of overview the impact of clozapine on the immune system in individuals with treatment-responsive and treatment-resistant schizophrenia.

Mounting evidence indicates the involvement of neuroinflammation in the development of schizophrenia (SCZ), but the potential role of astroglia in this phenomenon remains poorly understood. We assessed the molecular and functional consequences of inflammasome activation using induced pluripotent stem cell (iPSC)-derived astrocytes generated from SCZ patients and healthy controls (CTRL). Screening protein levels in astrocytes at baseline identified lower expression of the NLRP3-ASC complex in SCZ, but increased Caspase-1 activity upon specific NLRP3 stimulation compared to CTRL. Using transcriptional profiling, we found corresponding downregulations of NLRP3 and ASC/PYCARD in both iPSC-derived astrocytes, and in a large (n = 429) brain postmortem case-control sample. Functional analyses following NLRP3 activation revealed an inflammatory phenotype characterized by elevated production of IL-1β/IL-18 and skewed priming of helper T lymphocytes (Th1/Th17) by SCZ astrocytes. This phenotype was rescued by specific inhibition of NLRP3 activation, demonstrating its dependence on the NLRP3 inflammasome. Taken together, SCZ iPSC-astrocytes display unique, NLRP3-dependent inflammatory characteristics that are manifested via various cellular functions, as well as via dysregulated innate and adaptive immune responses.

Psychedelics have shown promising effects in several psychiatric diseases as demonstrated by multiple clinical trials. However, no clinical experiments on patients with schizophrenia have been conducted up to date, except for some old semi-anecdotal studies mainly performed in the time-span '50s-'60s. Notably, these studies reported interesting findings, particularly on the improvement of negative symptoms and social cognition. With no doubts the lack of modern clinical studies is due to the psychomimetic properties of psychedelics, a noteworthy downside that could worsen positive symptoms. However, a rapidly increasing body of evidence has suggested that the mechanisms of action of such compounds partially overlaps with the pathogenic underpinnings of schizophrenia but in an opposite way. These findings suggest that, despite being a controversial issue, the use of psychedelics in the treatment of schizophrenia would be based on a strong biological rationale. Therefore, the aim of our perspective paper is to provide a background on the old experiments with psychedelics performed on patients with schizophrenia, interpreting them in the light of recent molecular findings on their ability to induce neuroplasticity and modulate connectivity, the immune and TAARs systems, neurotransmitters, and neurotropic factors. No systematic approach was adopted in reviewing the evidence given the difficulty to retrieve and interpret old findings. Interestingly, we identified a therapeutic potential of psychedelics in schizophrenia adopting a critical point of view, particularly on negative symptoms and social cognition, and we summarized all the relevant findings. We also identified an eligible subpopulation of chronic patients predominantly burdened by negative symptoms, outlining possible therapeutic strategies which encompass very low doses of psychedelics (microdosing), carefully considering safety and feasibility, to pave the way to future clinical trials.

This study aims to investigate the genetic link between mental disorders-depression, schizophrenia (SCZ), and bipolar disorder (BIP)-and abdominal aortic aneurysm (AAA).

We first examined the genetic associations between AAA and mental disorders by analyzing global and local genetic correlations as well as shared genomic loci. Global genetic correlation was assessed using linkage disequilibrium score regression (LDSC) and the GeNetic cOVariance Analyzer (GNOVA), while local genetic correlation was analyzed using the SUPERGNOVA approach. To identify shared genetic variants, the pleiotropy-informed conditional and conjunctional false discovery rate (pleioFDR) method was applied. Subsequently, the univariate Mendelian Randomization (UMR) was employed to evaluate the causal relationship, complemented by multivariate MR (MVMR) to account for potential confounding biases. Additionally, mediation analysis was performed to determine whether known risk factors mediate the identified causal relationships.

Global correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95 % CI 1.071-1.504; p = 0.006) and SCZ (OR 1.047; 95 % CI 1.010-1.084; p = 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ's impact.

This study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N = 4,835) and UK Biobank (39-86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

There is growing evidence that interleukin (IL)-6 plays an important role in neurological and psychiatric disorders. This editorial comments on the study published in the recent issue of the World Journal of Psychiatry, which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence. The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities. IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory processes associated with epilepsy. Furthermore, IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy, highlighting its involvement in neuropsychiatric comorbidities. In summary, IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications. Future research should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes, stages and neuropsychiatric comorbidities of epilepsy, with the aim of developing more precise and effective interventions. Furthermore, the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epilepsy warrants further investigation.

Metabolic processes form the basis of the development, functioning and maintenance of the brain. Despite accumulating evidence of the vital role of metabolism in brain health, no study to date has comprehensively investigated the link between circulating markers of metabolic activity and in vivo brain morphology in the general population.

We performed uni- and multivariate regression on metabolomics and MRI data from 24,940 UK Biobank participants, to estimate the individual and combined associations of 249 circulating metabolic markers with 91 measures of global and regional cortical thickness, surface area and subcortical volume. We investigated similarity of the identified spatial patterns with brain maps of neurotransmitters, and used Mendelian randomization to uncover causal relationships between metabolites and the brain.

Intracranial volume and total surface area were highly significantly associated with circulating lipoproteins and glycoprotein acetyls, with correlations up to .15. There were strong regional associations of individual markers with mixed effect directions, with distinct patterns involving frontal and temporal cortical thickness, brainstem and ventricular volume. Mendelian randomization provided evidence of bidirectional causal effects, with the majority of markers affecting frontal and temporal regions.

The results indicate strong bidirectional causal relationships between circulating metabolic markers and distinct patterns of global and regional brain morphology. The generated atlas of associations provides a better understanding of the role of metabolic pathways in structural brain development and maintenance, in both health and disease.

Epilepsy is a prevalent chronic neurological disorder that can significantly impact patients' lives. The incidence and risk of psychosis in individuals with epilepsy are notably higher than in the general population, adversely affecting both the management and rehabilitation of epilepsy and further diminishing patients' quality of life. This review provides an overview of the classification and clinical features of psychosis of epilepsy, with the aim of offering insights and references for the clinical diagnosis and treatment of various types of psychosis of epilepsy. Additionally, we examine the potential pathophysiological mechanisms underlying the psychosis of epilepsy from three perspectives: neuroimaging, neurobiology, and genetics. The alterations in brain structure and function, neurotransmitters, neuroinflammatory mediators, and genetic factors discussed in this review may offer insights into the onset and progression of psychotic symptoms in epilepsy patients and are anticipated to inform the identification of novel therapeutic targets in the future.

Growth Differentiation Factor-15 (GDF-15) is a pleiotropic cytokine that plays a significant role in metabolism and inflammation. Elevated serum levels of GDF-15 have been associated with mood disorders. We propose that GDF-15 may potentially influence cognitive impairment and metabolism in male patients with chronic schizophrenia (CS), although there is limited research on this topic. This study compared serum GDF-15 levels in 72 male patients with CS and 85 healthy controls (HC). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), while cognitive performance was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The male CS patients performed worse than the healthy controls in both the total score and all subscales of the RBANS. Serum GDF-15 concentrations were significantly higher in the male CS patients compared to the healthy controls. Furthermore, the log-transformed serum GDF-15 concentrations in male CS patients were positively correlated with BMI and negatively correlated with Delayed Memory scores, Immediate Memory, and the total RBANS score. This preliminary study suggests that elevated serum GDF-15 levels in male patients with chronic schizophrenia may play a role in cognitive function and BMI regulation.

The pathogenesis of cognitive impairment in schizophrenia (SCZ) remains unclear. Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor (BDNF) levels play a crucial role in the psychopathology of SCZ. However, their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated.

To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ.

The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ (SCZ group) and 80 healthy controls (HCs group) at the Huzhou Third Municipal Hospital between August 2021 and September 2023. ELISA was employed to measure the serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, and BDNF. The Chinese brief cognitive test (C-BCT) and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms.

Compared to the HC group, the SCZ group exhibited elevated IL-1β and IL-6 levels, decreased BDNF levels, and reduced C-BCT scores (all P < 0.001). In SCZ, BDNF was negatively correlated with IL-6 (r = -0.324, P < 0.05). Information processing speed was negatively correlated with IL-6 (r = -0.315, P < 0.05) and positively with BDNF (r = 0.290, P < 0.05); attention, working memory, comprehensive ability, and executive function were negatively correlated with IL-1β and IL-6 (all P < 0.05) and positively with BDNF (all P < 0.05). Multiple regression analysis showed IL-6 influenced C-BCT dimensions (β = -0.218 to -0.327, all P < 0.05); attention and executive ability were influenced by IL-1β (β = -0.199 to -0.261, all P < 0.05); comprehensive executive ability was influenced by BDNF (β = 0.209, P < 0.05).

Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

Inflammatory proteins are implicated in psychiatric disorders, but the causality and underlying mechanisms remain unclear.

We conducted bidirectional Mendelian randomization (MR) using genetic variants from genome-wide association studies (GWAS) for 91 inflammatory proteins (N = 14 824) and 11 psychiatric disorders (N = 9725 to 1 035 760). The primary analysis used the inverse variance weighted (IVW) method, with additional sensitivity analyses to confirm robustness. A two-step MR approach assessed whether brain imaging-derived phenotypes (IDPs) mediated the observed effects.

Forward MR analysis found the protective effect of CD40 on schizophrenia (SCZ) (IVW OR = 0.90, P = 5.29 × 10-6) and bipolar disorder (BD) (IVW OR = 0.89, P = 5.08 × 10-6). Reverse MR demonstrated that increased genetic risk of Tourette's syndrome (TS) was associated with reduced Fms-associated tyrosine kinase 3 ligand (Flt3L) levels (Flt3L) (Wald Ratio beta = -0.42, P = 1.99 × 10-7). The protective effect of CD40 on SCZ was partially mediated by the modulation of fractional anisotropy (FA) values in the right and left superior frontal occipital fasciculus, with mediation proportions of 9.6% (P = .025) and 11.5% (P = .023), respectively.

CD40 exerts an immunoprotective effect on SCZ and BD, and the effect of CD40 on SCZ was partially mediated through modulation of FA values in the superior frontal occipital fasciculus. These findings enhance comprehension of the etiology of these psychiatric conditions and underscore the promise of therapeutic strategies aimed at inflammatory proteins.

Schizophrenia (SCZ) is a heterogeneous psychiatric disorder that is poorly treated by current therapies. Emerging evidence indicates that SCZ is closely correlated with a persistent neuroinflammation. α-linolenic acid (ALA) is highly concentrated in the brain and represents a modulator of the immune system by decreasing the inflammatory response in chronic metabolic diseases. This study was first designed to investigate the potential role of dietary ALA on cognitive function and neuroinflammation in mice with SCZ.

In vivo, after 2 weeks of modeling, mice were treated with dietary ALA treatment for 6 weeks. In vitro, inflammation model was created using lipopolysaccharide as an inducer in BV2 microglial cells.

Our results demonstrated that ALA alleviated cognitive impairment and enhanced synaptic plasticity in mice with SCZ. Moreover, ALA mitigated systematic and cerebral inflammation through elevating IL-10 and inhibiting IL-1β, IL-6, IL-18 and TNF-α. Furthermore, ALA notably inhibited microglia and pro-inflammatory monocytes, as well as microglial activation andpolarization. Mechanistically, ALA up-regulated the expressions of G protein coupled receptor (GPR) 120 and associated β-inhibitor protein 2 (β-arrestin2), accompanied by observable weakened levels of transforming growth factor-β activated kinase 1 (TAK1), NF-κB p65, cysteine proteinase-1 (caspase-1), pro-caspase-1, associated speck-like protein (ASC) and NLRP3. In vitro, ALA directly restrained the inflammation of microglia by decreasing the levels of pro-inflammatory factors and regulating microglial polarization via GPR120-NF-κB/NLRP3inflammasome signaling pathway, whereas AH7614 definitely eliminated this anti-inflammatory effect of ALA.

Dietary ALA ameliorates microglia-mediated neuroinflammation by suppressing the NF-κB/NLRP3 pathway via binding GPR120-β-arrestin2.

Psychiatric disorders pose an enormous economic and emotional burden on individuals, their families, and society. Given that the current analysis of the pathogenesis of psychiatric disorders remains challenging and time consuming, elucidating modifiable risk factors is crucial for the diagnosis and management of psychiatric disorders. However, inferring causal risk factors for these disorders from disparate data sources is challenging due to constraints in data collection and analytical capabilities.

By leveraging the largest available genome-wide association study summary statistics for 10 psychiatric disorders and compiling an extensive set of risk factor datasets, including 71 psychiatric disorder-specific phenotypes, 3935 brain imaging traits, and over 30 brain tissue/cell-specific quantitative trait loci datasets (covering 6 types of quantitative trait loci), we performed comprehensive Mendelian randomization analyses to explore the potential causal links between various exposures and psychiatric outcomes using genetic variants as instrumental variables.

After Bonferroni correction for multiple testing, we identified multiple potential risk factors for psychiatric disorders (including phenotypic-level and molecular-level traits) and provided robust Mendelian randomization evidence that supports these associations utilizing rigorous sensitivity analyses and colocalization analyses. Furthermore, we have established the PsyRiskMR database (http://bioinfo.ahu.edu.cn/PsyRiskMR/), which serves as an interactive platform for showcasing and querying risk factors for psychiatric disorders.

Our study offers a user-friendly PsyRiskMR database for the research community to browse, search, and download all Mendelian randomization results, potentially revealing new insights into the biological etiology of psychiatric disorders.

The maternal immune activation hypothesis has gained attention over the past 2 decades as a potential contributor to the etiology of autism. This hypothesis posits that maternal conditions associated with inflammation during pregnancy may increase the risk of autism in offspring. Autism is highly heritable, and causal environmental contributors to autism largely remain elusive. We review studies on maternal conditions during pregnancy, all associated with some degree of systemic inflammation, namely maternal infections, autoimmunity, and high body mass index. We also review studies of inflammatory markers in biological samples collected from mothers during pregnancy or from neonates and their relationship with autism assessed in children later in life. Recent reports indicate familial clustering of autism, autoimmunity, and infections, as well as genetic correlations between autism and aspects of immune function. Given this literature, there is an apparent risk of confounding of the reported associations between inflammatory exposures and autism by familial genetic factors in both clinical and epidemiological cohort studies. We highlight recent studies that have attempted to address potential confounding to assess evidence of causal effects of inflammation during early life in autism.

Schizophrenia (SZ) is a severe mental disorder with complex origins. Observational studies suggested that inflammatory factors may play a role in the pathophysiology of SZ and we aim to investigate the potential genetic connection between them by examining the causal impact of circulating inflammatory proteins on SZ.

We utilized Mendelian randomization (MR) analysis to assess the causal relationship between circulating inflammatory proteins and SZ and the GWAS summary datasets were sourced from public databases. The SZ dataset comprised 74,776 cases and 101,023 controls, while the summary results for 91 plasma proteins in 14,824 participants were obtained through the Olink Target platform. Moreover, to identify and evaluate potential drug targets, we searched the Drug-Gene Interaction Database (DGIdb).

The results of the MR study confirmed that nine inflammatory proteins had a causal effect on SZ. Among these proteins, IL1A (OR: 0.93), TNFB (OR: 0.94), TNFSF14 (OR: 0.96), and CD40 (OR: 0.95) exhibited protective effects against SZ. Conversely, CCL23 (OR: 1.04), CCL19 (OR: 1.04), 4EBP1 (OR: 1.06), TWEAK (OR: 1.08), and DNER (OR: 1.10) were associated with an increased risk of SZ. The MR-Egger and weighted median methods also supported the direction of these effects. According to the Gene-Drug analysis, LTA, IL1A, CD40, and 4EBP1 can serve as drug targets.

Our study established causal relationships between circulating inflammatory proteins and SZ. It may be beneficial to personalize the treatment of SZ by incorporating inflammation management into the treatment regimen.

Acute and transient psychotic disorder (ATPD), a psychosis frequently diagnosed, can potentially evolve into chronic conditions like schizophrenia (SCZ) and other mental disorders. This study aimed to develop a predictive model based on clinical data to forecast the transition from ATPD to SCZ and to identify the predictive factors.

According to the diagnostic criteria issued by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), 396 inpatients diagnosed with ATPD were collected in this study. The Cox proportional-hazards regression model was performed using demographic data, clinical characteristics, and inflammatory markers to identify independent predictors for subsequent diagnostic transition (SDT) to SCZ.

During the follow-up period, 43.69% (n = 173) of ATPD patients had their diagnoses revised to SCZ. The multivariate Cox regression analysis identified post-treatment monocyte count, post-treatment monocyte/lymphocyte ratio (MLR), and the presence of schizophreniform symptoms as significant predictors for the diagnostic revision. Time-dependent receiver operating characteristic (TimeROC) analyses were developed. The AUC value at the 5-year follow-up was 0.728 for combined predictors, 0.702 for post-treatment monocyte count, 0.764 for post-treatment MLR, and 0.535 for the presence of schizophreniform symptoms.

The combined predictors had good predictive ability for the diagnostic transition from acute and transient psychotic disorder to schizophrenia.

Importin α4, which is encoded by the Kpna4 gene, is a well-characterized nuclear-cytoplasmic transport factor known to mediate transport of transcription factors including NF-κB. Here, we report that Kpna4 knock-out (KO) mice exhibit psychiatric disorder-related behavioral abnormalities such as anxiety-related behaviors, decreased social interaction, and sensorimotor gating deficits. Contrary to a previous study predicting attenuated NF-κB activity as a result of Kpna4 deficiency, we observed a significant increase in expression levels of NF-κB genes and proinflammatory cytokines such as TNFα, Il-1β or Il-6 in the prefrontal cortex or basolateral amygdala of the KO mice. Moreover, examination of inflammatory responses in primary cells revealed that Kpna4 deficient cells have an increased inflammatory response, which was rescued by addition of not only full length, but also a nuclear transport-deficient truncation mutant of importin α4, suggesting contribution of its non-transport functions. Furthermore, RNAseq of sorted adult microglia and astrocytes and subsequent transcription factor analysis suggested increases in polycomb repressor complex 2 (PRC2) activity in Kpna4 KO cells. Taken together, importin α4 deficiency induces psychiatric disorder-related behavioral deficits in mice, along with an increased inflammatory response and possible alteration of PRC2 activity in glial cells.

Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression.

Resting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis (n = 53) and recent-onset depression (n = 55) from the European Union/Seventh Framework Programme-funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group.

A repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate.

We identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders.

Schizophrenia diagnosis and admission history were associated with a polygenic score (PGS) for schizophrenia based on a subset of variants that act by modifying the expression of genes whose expression is also modified by antipsychotics. This gene set was enriched in cytokine production. Interleukin-6 (IL-6) is the only cytokine whose plasma levels were associated both with schizophrenia diagnosis and with acute decompensations in the largest meta-analysis. Therefore, we hypothesized that an IL-6 PGS, but not other cytokines PGSs, would be associated with schizophrenia chronicity/psychiatric admissions. Using the IL-6 PGS model from The PGS Catalog, IL-6 PGS was calculated in 427 patients with schizophrenia and data regarding admission history. Association between IL-6 PGS and chronicity, measured as number and duration of psychiatric admissions, or ever readmission was analyzed by multivariate ordinal and logistic regression, respectively. Specificity of results was assessed by analysis of PGSs from the other cytokines at The PGS Catalog with meta-analytic evidence of association with schizophrenia diagnosis or acute decompensations, IL-1RA, IL-4, IL-8, and IL-12. IL-6 PGS was associated with schizophrenia chronicity, explaining 1.51% of variability (OR = 1.29, 95% CI 1.07-1.55, P = 0.007). There was no association with ever readmission. Other cytokines PGSs were not associated with chronicity. Association with IL-6 PGS was independent of association with schizophrenia PGS. Our results provide evidence that genetically regulated higher levels of IL-6 are involved in schizophrenia chronicity, highlighting the relevance of immunity processes for a subgroup of patients.

Previous studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship.

Firstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.

The results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates.

This study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

Accumulating evidence indicates that individuals with chronic kidney disease (CKD) are at an increased risk of experiencing depressive disorders, which may accelerate its progression. However, the relationship between the triglyceride-glucose (TyG) index and depression in CKD individuals remains unclear. Therefore, this cross-sectional study aimed to assess whether such a relationship exists. To this end, the CKD cohort of the National Health and Nutrition Examination Survey from 2005 to 2020 was analyzed using multivariable logistic regression analyses and a generalized additive approach. A recursive algorithm was employed to pinpoint the turning point, constructing a dual-segment linear regression model. The study included 10,563 participants. After controlling for all variables, the odds ratios and 95% confidence intervals indicated a 1.24 (range, 1.09-1.42) relationship between the TyG index and depression in the CKD cohort. The findings underscored an asymmetrical association, with a pivotal value at a TyG index 9.29. Above this threshold, the adjusted odds ratio (95% confidence interval) was 1.10 (range, 0.93-1.31). This relationship was significant among the obese subgroups. The study results highlight the complex relationship between the TyG index and depression among American adults with CKD.

The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis and treatment. While recent research has established a clear association between immune function and schizophrenia, the causal relationship between the two remains elusive.

We employed a bidirectional two-sample Mendelian randomization approach to investigate the causal relationship between schizophrenia and 731 immune cell traits by utilizing public GWAS data. We further validated the causal relationship between schizophrenia and six types of white cell measures.

We found the overall causal effects of schizophrenia on immune cell traits were significantly higher than the reverse ones (0.011 ± 0.049 vs 0.001 ± 0.016, p < 0.001), implying that disease may lead to an increase in immune cells by itself. We also identified four immune cell traits that may increase the risk of schizophrenia: CD11c+ monocyte %monocyte (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03~1.09, FDR = 0.027), CD11c+ CD62L- monocyte %monocyte (OR:1.06, 95% CI: 1.03~1.09, FDR = 0.027), CD25 on IgD+ CD38- naive B cell (OR:1.03, 95% CI:1.01~1.06, FDR = 0.042), and CD86 on monocyte (OR = 1.04, 95% CI:1.01~1.06, FDR = 0.042). However, we did not detect any significant causal effects of schizophrenia on immune cell traits. Using the white blood cell traits data, we identified that schizophrenia increases the lymphocyte counts (OR:1.03, 95%CI: 1.01-1.04, FDR = 0.007), total white blood cell counts (OR:1.02, 95%CI: 1.01-1.04, FDR = 0.021) and monocyte counts (OR:1.02, 95%CI: 1.00-1.03, FDR = 0.034). The lymphocyte counts were nominally associated with the risk of schizophrenia (OR:1.08,95%CI:1.01-1.16, P=0.019).

Our study found that the causal relationship between schizophrenia and the immune system is complex, enhancing our understanding of the role of immune regulation in the development of this disorder. These findings offer new insights for exploring diagnostic and therapeutic options for schizophrenia.

Schizophrenia is a complex and disabling mental disorder that represents one of the most important challenges for neuroimaging research. There were many attempts to understand these basic mechanisms behind the disorder, yet we know very little. By employing machine learning techniques with age-matched samples from the auditory oddball task using multi-site functional magnetic resonance imaging (fMRI) data, this study aims to address these challenges.

The study employed a three-stage model to gain a better understanding of the neurobiology underlying schizophrenia and techniques that could be applied for diagnosis. At first, we constructed four-level hierarchical sets from each fMRI volume of 34 schizophrenia patients (SZ) and healthy controls (HC) individually in terms of hemisphere, gyrus, lobes, and Brodmann areas. Second, we employed statistical methods, namely, t-tests and Pearson's correlation, to assess the group differences in cortical activation. Finally, we assessed the predictive power of the brain regions for machine learning algorithms using K-nearest Neighbor (KNN), Naive Bayes, Decision Tree (DT), Random Forest (RF), Support Vector Machines (SVMs), and Extreme Learning Machine (ELM).

Our investigation depicts promising results, obtaining an accuracy of up to 84% when applying Pearson's correlation-selected features at lobes and Brodmann region level (81% for Gyrus), as well as Hemispheres involving different stages. Thus, the results of our study were consistent with previous studies that have revealed some functional abnormalities in several brain regions. We also discovered the involvement of other brain regions which were never sufficiently studied in previous literature, such as the posterior lobe (posterior cerebellum), Pyramis, and Brodmann Area 34.

We present a unique and comprehensive approach to investigating the neurological basis of schizophrenia in this study. By bridging the gap between neuroimaging and computable analysis, we aim to improve diagnostic accuracy in patients with schizophrenia and identify potential prognostic markers for disease progression.

Schizophrenic patients are prone to violence, frequent recurrence, and difficult to predict. Emotional and behavioral abnormalities during the onset of the disease, resulting in active myocardial enzyme spectrum.

To explored the expression level of myocardial enzymes in patients with schizophrenia and its predictive value in the occurrence of violence.

A total of 288 patients with schizophrenia in our hospital from February 2023 to January 2024 were selected as the research object, and 100 healthy people were selected as the control group. Participants' information, clinical data, and laboratory examination data were collected. According to Modified Overt Aggression Scale score, patients were further divided into the violent (123 cases) and non-violent group (165 cases).

The comparative analysis revealed significant differences in serum myocardial enzyme levels between patients with schizophrenia and healthy individuals. In the schizophrenia group, the violent and non-violent groups also exhibited different levels of serum myocardial enzymes. The levels of myocardial enzymes in the non-violent group were lower than those in the violent group, and the patients in the latter also displayed aggressive behavior in the past.

Previous aggressive behavior and the level of myocardial enzymes are of great significance for the diagnosis and prognosis analysis of violent behavior in patients with schizophrenia. By detecting changes in these indicators, we can gain a more comprehensive understanding of a patient's condition and treatment.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function.

Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility.

Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed.

Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.