Schizophrenia is a complex psychiatric disorder traditionally linked to neurotransmitter imbalances, but growing evidence implicates neuroinflammation as a key factor in its pathogenesis. Core pathological features include aberrant microglial activation, elevated proinflammatory cytokines (e.g., IL-6, TNF-α), blood-brain barrier disruption, and oxidative stress, all contributing to neuronal dysfunction. Genetic, epigenetic, and neurodevelopmental abnormalities further intensify the link between neuroinflammation and clinical symptoms, including cognitive deficits and positive/negative symptoms. Therapeutically, anti-inflammatory strategies show promise: Non-steroidal anti-inflammatory drugs inhibit the cyclooxygenase pathway; minocycline modulates microglial activity; cytokine inhibitors regulate immune responses; and antioxidants and mitochondrial agents (e.g., N-acetylcysteine, omega-3 fatty acids) reduce oxidative damage. Emerging approaches such as cannabidiol and nanodelivery systems also demonstrate anti-inflammatory and neuroprotective potential. However, long-term safety, dosage optimization, and individual variability remain to be fully validated. Future research should integrate single-cell genomics, neuroimaging, and biomarker stratification to elucidate neuroinflammatory mechanisms and enable precise combination therapies. Combining immunomodulatory and neurotransmitter-based strategies may overcome the limitations of traditional antipsychotics and improve clinical outcomes.

Some studies suggest that Toxoplasma gondii infection may increase the risk of developing schizophrenia. Determining changes in blood biomarker concentrations may provide new insights into the underlying mechanisms associated with Toxoplasma gondii infection in schizophrenia. The aim of the study was to evaluate the concentrations of several serum neurobiological and immune parameters and to identify changes in their concentrations that could potentially be indicators of psychopathologic changes in infection. The concentration of biomarkers was determined in serum from patients with schizophrenia (uninfected n = 50, infected n = 30) and from mentally healthy volunteers (uninfected n = 51, infected n = 29) using multiplex analysis. A number of psychometric scales have been applied to assess the cognitive functioning. No significant associations were between schizophrenia and Toxoplasma gondii infection (p = 0.54; OR = 1.18; 95% CI = 0.69-2.01). However, infected patients with schizophrenia had more severe cognitive impairment compared to uninfected schizophrenia patients (PDQ-20). The group of biomarkers has been identified whose concentration changes were observed only between Toxoplasma gondii-infected healthy individuals and individuals with schizophrenia (neurobiological indicators KLK6, UCHL1, Amyloid beta 1-42 and neurogranin; anti-inflammatory cytokine IL-10; chemokines IL-8 and MIP-1 beta), but not between uninfected groups. The hypothesis was proposed that it is possible to use these indices as indicators of the development of schizophrenic psychopathology in Toxoplasma gondii infection. The associations of blood biomarker concentrations with IgA and IgM antibody levels (chemokine RANTES) and with schizophrenia symptoms (hormone-like messenger KLK6; chemokines IP-10 and GRO alpha) were found. Toxoplasma gondii reactivation leads to a decrease in negative symptomatology and reduced FGF-21 levels in patients with schizophrenia, and increased CNTF and NGF beta levels compared to the latent form.

Cognitive impairment in schizophrenia occurs in the early stages of the disease and is closely associated with prognosis. Alleviation of cognitive impairment in schizophrenia faces major challenges owing to the lack of preventive and therapeutic drugs that are novel and effective. Urolithin A (UA) is a gut microbial metabolite of ellagic acid that has demonstrated neuroprotective effects in multiple neurological disease models. Nonetheless, the neuromodulatory role of UA in schizophrenia is yet to be elucidated. Wistar rat pups were separated from their mothers for 24 h on postnatal days (PNDs) 9-10 to establish an early-life stress model. The pups were pretreated with UA at different administration times (2, 4, and 6 weeks) and doses (50, 100, and 150 mg/kg) from adolescence (PND29). Behavioral tests were performed after the end of the administration. Subsequently, hippocampal samples were collected for histopathological and molecular evaluations. Male offspring rats subjected to maternal separation exhibited increased sensitivity to prepulse inhibition and cognitive impairment, accompanied by severe neuroinflammation and impaired neurogenesis. However, UA attenuated maternal separation-induced prepulse inhibition deficits and cognitive impairments and restored hippocampal neurogenesis in a dose-dependent manner. Furthermore, UA pretreatment preserved dendritic spine density, synapses, and presynaptic vesicles. In addition, it exerted anti-inflammatory effects by inhibiting microglial activation and expression of the proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. Potential mechanisms included upregulation of brain-derived neurotrophic factor protein expression and activation of the extracellular signal-regulated kinase signaling pathway. This study is the first preclinical evaluation of the effects of UA on cognitive impairment in schizophrenia. The findings suggest that changes in cognitive function linked to schizophrenia are driven by the interaction among neuroinflammation, neurogenesis, and synaptic plasticity and that UA has the potential to reverse these processes. These observations provide evidence for future clinical trials of UA as a dietary supplement for preventing schizophrenia.

The role of degree centrality (DC) in schizophrenia (SCZ), its trajectory following pharmacological treatment, and its potential as a prognostic biomarker and genetic mechanism remain unclear.

We recruited 51 healthy controls (HC) and 56 patients with SCZ. Additionally, the SCZ patients underwent three months of antipsychotic medication treatment. We collected resting-state functional magnetic resonance imaging data, clinical variables, and conducted analyses using support vector machines, support vector regression, and gene expression correlation analysis.

Our study revealed that SCZ patients had generally reduced DC values in the cerebral cortex compared to HC at baseline, with increased DC values observed in the left occipital gyrus. After three months of treatment, SCZ patients exhibited a significant decrease in DC values in the left fusiform gyrus and an increase in the left inferior parietal gyrus. Variations in DC values in SCZ patients were associated with multiple genes, primarily enriched in molecular functions.

Changes in DC values in the right inferior occipital/fusiform gyrus and right calcarine/middle occipital gyrus may serve as neuroimaging markers to differentiate between HC and SCZ patients. Additionally, DC values in the left middle/postcentral gyrus could be used to predict treatment outcomes. Transcriptome-neuroimaging spatial correlation analysis provides valuable insights into the neurobiological mechanisms underlying SCZ pathology.

Toxoplasmosis is a foodborne zoonotic parasitic disease caused by Toxoplasma gondii, which seriously threatens to human health and causes economic losses. At present, there is no effective vaccine strategy for the prevention and control of toxoplasmosis. T. gondii rhoptry proteins (ROPs) are important proteins secreted by the parasite during the early stage of invasion into host cells. In this study, we constructed six individual plasmids (pVAX1-ROP2, pVAX1-ROP5, pVAX1-ROP9, pVAX1-ROP16, pVAX1-ROP17, and pVAX1-ROP18) encoding T. gondii rhoptry proteins and then used an equimolar amount of each as a vaccine cocktail. Following booster immunization, serum antibody levels, splenic lymphocyte proliferation, cytokine production, and survival time after infection with T. gondii RH strain were measured in immunized mice. The results showed that the mice immunized with the DNA vaccine cocktail developed a higher level of the specific anti-T. gondii IgG in serum and the cytokines such as IFN-γ, IL-2, IL-12, and IL-4 (P < 0.01). The stimulation index (SI) of spleen lymphocytes (P < 0.01), the frequencies of CD4+ T lymphocytes (P < 0.01), and the ratio of CD4+/CD8+ T lymphocytes (P < 0.05 or P < 0.01) in the vaccine-immunized mice were significantly increased compared to the control group. After challenge with the virulent T. gondii RH strain tachyzoites, the survival time of mice in the DNA vaccine cocktail group (18.1 ± 1.81 d) was significantly longer (P < 0.01) than that in the control group (8.4 ± 1.02 or 7.9 ± 0.83 d). The results indicated that the DNA vaccine cocktail could elicit strong humoral and cellular immune responses in mice and could also improve the resistance of mice to acute T. gondii infection.

The intervention value of a drug-psycho-social-skill model on medication compliance and cognitive ability in patients with chronic schizophrenia was unknown.

To explore the intervention value of a drug-psycho-social-skill model on medication compliance and cognitive ability in patients with chronic schizophrenia.

Overall, 98 out-patients and in-patients with chronic schizophrenia treated in our hospital from February 2022 to January 2023 were included and randomly divided into the study (50 patients) and control groups (48 patients). For 3 months, the control group was treated with conventional drugs, and the research group with a comprehensive intervention model of drug-psychology-society-skills. Data were obtained for the mini mental assessment scale (MMSE), Montreal cognitive assessment scale (MoCA), positive and negative symptom scale, insight and treatment attitude scale, cognitive ability scale and social skills [personal and social function scale (PSP)]. The adverse reactions were observed.

After the intervention, the MMSE and MoCA scores improved in both groups. MoCA scores in the study group (26.58 ± 3.21) were significantly (P < 0.05) higher than those in the control group (24.68 ± 3.02), MMSE scores were not significantly higher. Post-intervention, positive and negative symptom scores improved in both groups, and the positive and negative symptom scores in the study group [(12.01 ± 2.58) and (32.51 ± 2.11)] were significantly (P < 0.05) different than those in the control group [(14.54 ± 2.33) and (33.74 ± 2.55)]. Post-intervention, insight and treatment attitudes questionnaire scores of both groups were improved and compared with the control group (7.97 ± 3.02), the study group (13.56 ± 6.35) had significantly (P < 0.05) higher scores. Post-intervention, the MATRICS consensus cognitive battery score of both groups was improved and compared with the control group (38.44 ± 6.23), the score of the study group was significantly (P < 0.05) increased (43.51 ± 6.01). Post-intervention, the PSP score of the study group (78.38 ± 6.63) was significantly (P < 0.05) higher than that of the control group (74.52 ± 7.01). During the intervention period, the incidence of adverse reactions in the study group was 6.25%, not significantly different from that in the control group (8.33%). During the intervention, both groups experienced adverse reactions, with no significant difference between groups (P > 0.05).

The comprehensive intervention model based on drug-psychology-society-skills has obvious intervention effects on patients with chronic schizophrenia, which improves their cognitive ability and reduces their positive and negative symptoms. Simultaneously, it improves the self-knowledge of patients, improves their attitude toward treatment, effectively promotes the recovery of patients' social functions, and is safe. Therefore, it is worthy of being vigorously promoted and widely used in clinics.

Readmissions are an indicator of hospital care quality; a high readmission rate is associated with adverse outcomes. This leads to an increase in healthcare costs and quality of life for patients. Developing predictive models for hospital readmissions provides opportunities to select treatments and implement preventive measures. The aim of this study is to develop predictive models for the readmission risk of patients with schizophrenia, combining the particle swarm optimization (PSO) algorithm with machine learning classification algorithms. The database used in the study includes a total of 6089 readmission records of patients with schizophrenia. These records were collected from 11 public hospitals in Castilla and León, Spain, in the period 2005-2015. The results of the study show that the Random Forest algorithm combined with PSO achieved the best results across the evaluated performance metrics: AUC = 0.860, recall = 0.959, accuracy = 0.844, and F1-score = 0.907. The development of these new models contributes to -improving patient care. Additionally, they enable preventive measures to reduce costs in healthcare systems.

First-episode schizophrenia (FES) is a progressive psychiatric disorder influenced by genetics, environmental factors, and brain function. The functional gradient deficits of drug-naïve FES and its relationship to gene expression profiles and treatment outcomes are unknown.

In this study, we engaged a cohort of 116 FES and 100 healthy controls (HC), aged 7 to 30 years, including 15 FES over an 8-week antipsychotic medication regimen. Our examination focused on primary-to-transmodal alterations in voxel-based connection gradients in FES. Then, we employed network topology, Neurosynth, postmortem gene expression, and support vector regression to evaluate integration and segregation functions, meta-analytic cognitive terms, transcriptional patterns, and treatment predictions.

FES displayed diminished global connectome gradients (Cohen's d = 0.32-0.57) correlated with compensatory integration and segregation functions (Cohen's d = 0.31-0.36). Predominant alterations were observed in the default (67.6%) and sensorimotor (21.9%) network, related to high-order cognitive functions. Furthermore, we identified notable overlaps between partial least squares (PLS1) weighted genes and dysregulated genes in other psychiatric conditions. Genes linked with gradient alterations were enriched in synaptic signaling, neurodevelopment process, specific astrocytes, cortical layers (layer II and IV), and developmental phases from late/mid fetal to young adulthood. Additionally, the onset age influenced the severity of FES, with discernible differences in connection gradients between minor- and adult-FES. Moreover, the connectivity gradients of FES at baseline significantly predicted treatment outcomes.

These results offer significant theoretical foundations for elucidating the intricate interplay between macroscopic functional connection gradient changes and microscopic transcriptional patterns during the onset and progression of FES.

The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms.

Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 μM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors.

Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1β, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model.

AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.

The gut‑microbiota‑brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut‑microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early‑life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first‑episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis.

In a blinded manner, we assessed the presence of anti-Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis (n = 29); 2) prodromal participants (n = 16); 3) children or adolescents with psychosis (n = 7); 4) adults with psychosis (n = 44); and 5) relatives of a participant with psychosis (n = 20).

There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. berkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18).

In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection.

Toxoplasmosis is a pathological condition induced by the parasite, Toxoplasma gondii (T. gondii), which has a notable affinity for the cellular components of the central nervous system. Over the decades, the relationship between toxoplasmosis and the development of psychiatric disorders has generated profound interest within the scientific community. Whether considering immunocompetent or immunocompromised patients, epidemiological studies suggest that exposure to T. gondii may be associated with a higher risk of certain psychiatric disorders. However, there are extensive debates regarding the exact nature of this association and how T. gondii is involved in the pathogenesis of these disorders. Toxoplasmosis has long been considered an asymptomatic infection among immunocompetent patients. However, there appears to be an association between chronic brain infection with T. gondii and alterations in patient neuronal architecture, neurochemistry and behavior. The present review aimed to compile statements and pathophysiological hypotheses regarding the potential association between toxoplasmosis and psychotic disorders. Further research is necessary for understanding the potential relationship of T. gondii infection and psychotic disorders.

How has schizophrenia, a condition that significantly reduces an individual's evolutionary fitness, remained common across generations and cultures? Numerous theories about the evolution of schizophrenia have been proposed, most of which are not consistent with modern epidemiological and genetic evidence. Here, we briefly review this evidence and explore the cliff edge model of schizophrenia. It suggests that schizophrenia is the extreme manifestation of a polygenic trait or a combination of traits that, within a normal range of variation, confer cognitive, linguistic, and/or social advantages. Only beyond a certain threshold, these traits precipitate the onset of schizophrenia and reduce fitness. We provide the first mathematical model of this qualitative concept and show that it requires only very weak positive selection of the underlying trait(s) to explain today's schizophrenia prevalence. This prediction, along with expectations about the effect size of schizophrenia risk alleles, are surprisingly well matched by empirical evidence. The cliff edge model predicts a dynamic change of selection of risk alleles, which explains the contradictory findings of evolutionary genetic studies.

Although some findings indicate that yoga can reduce stress and anxiety, many studies present mixed results. The potential of yoga interventions to alleviate anxiety, including the mechanisms and boundary conditions by which it does so, is an under-researched topic. Anxiety is often divided into "state anxiety" and "trait anxiety," the former being a temporary reaction to stressful events, while the latter is a more stable personality feature that responds to adverse situations or perceived threats.

This study investigates whether a yin yoga intervention delivered online reduces state anxiety immediately after each yoga session and whether the anxiety levels are significantly lower at the end of the 10-week yoga intervention than at the beginning of the study. We also predicted no effect of yin yoga intervention on trait anxiety. The study was conducted during the COVID-19 pandemic when participants (N = 48 Latvian women) experienced heightened anxiety levels.

This study shows that a ten-week online yin yoga intervention significantly reduced state anxiety in the intervention group compared with the control group. State anxiety levels also significantly decreased after each yin yoga session, providing more support for the anxiety-reducing effect of yin yoga. In contrast, yoga participation did not cause differences in trait anxiety between the control and intervention groups, even though trait anxiety decreased in the intervention group and increased in the control group over the study period.

The positive effects of yin yoga on state anxiety indicate the potential of yin yoga intervention as a first-line treatment to control and reduce state anxiety, with possible additional effects on trait anxiety.

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients' self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

The gastrointestinal tract is embedded with microorganisms of numerous genera, referred to as gut microbiota. Gut microbiota has multiple effects on many body organs, including the brain. There is a bidirectional connection between the gut and brain called the gut-brain-axis, and these connections are formed through immunological, neuronal, and neuroendocrine pathways. In addition, gut microbiota modulates the synthesis and functioning of neurotransmitters. Therefore, the disruption of the gut microbiota in the composition or function, which is known as dysbiosis, is associated with the pathogenesis of many mental disorders, such as schizophrenia, depression, and other psychiatric disorders. This review aims to summarize the modulation role of the gut microbiota in 4 prominent neurotransmitters (tryptophan and serotonergic system, dopamine, gamma-aminobutyric acid, and glutamate), as well as its association with 4 psychiatric disorders (schizophrenia, depression, anxiety disorders, and autism spectrum disorder). More future research is required to develop efficient gut-microbiota-based therapies for these illnesses.

Schizophrenia is a complex disease related to combination and interactions between genetic and environmental factors, with an epigenetic influence. After the development of the first mono-factorial animal models of schizophrenia (1-hit), that reproduced patterns of either positive, negative and/or cognitive symptoms, more complex models combining two factors (2-hit) have been developed to better fit with the multifactorial etiology of the disease. In the two past decades, a new way to design animal models of schizophrenia have emerged by adding a third hit (3-hit). This review aims to discuss the relevance of the risk factors chosen for the tuning of the 3-hit animal models, as well as the validities measurements and their contribution to schizophrenia understanding. We intended to establish a comprehensive overview to help in the choice of factors for the design of multiple-hit animal models of schizophrenia.

A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. Specific microbes that have been associated or potentially associated with at least one of these conditions include Aspergillus, Babesia, Bartonella, Borna disease virus, Borrelia burgdorferi (Lyme disease), Candida, Chlamydia, coronaviruses (e.g., SARS-CoV-2), Cryptococcus neoformans, cytomegalovirus, enteroviruses, Epstein-Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, Mycoplasma, Plasmodium, rubella virus, Group A Streptococcus (PANDAS), Taenia solium, Toxoplasma gondii, Treponema pallidum (syphilis), Trypanosoma, and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.

Data on schizophrenia (SZ), epilepsy (EPD) and bipolar disorders (BPD) suggested an association of DNMT1 overexpression whereas certain variants of the gene were predicted to result in its increased expression in autism spectrum disorder (ASD). In addition, loss of DNMT1 in frontal cortex resulted in behavioral abnormalities in mice. Here we investigated the effects of increased as well as lack of DNMT1 expression using Dnmt1tet/tet neurons as a model for abnormal neurogenesis and 10,861 genes showing transcript level dysregulation in datasets from the four disorders. In case of overexpression, 3,211 (∼ 30%) genes were dysregulated, affecting pathways involved in neurogenesis, semaphorin signaling, ephrin receptor activity, etc. A disproportionately higher proportion of dysregulated genes were associated with epilepsy. When transcriptome data of Dnmt1tet/tet neurons treated with doxycycline that downregulated DNMT1 was used, 3,356 genes (∼31%) were dysregulated with a significant proportion involved in pathways similar to those in untreated cells. Both conditions resulted in ∼68% of dysregulated genes wherein a majority showed similar patterns of transcript level changes. Among the genes with transcripts returning to normal levels, ribosome assembly/biogenesis was most significant whereas in absence of DNMT1, a new set of 903 genes became dysregulated and are involved in similar pathways as mentioned above. These findings provide support for overexpression of DNMT1 as well as its downregulation as risk factor for the four disorders and that its levels within a tight range are essential for normal neurodevelopment/mental health.

Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.

Catechol-O-methyl transferase (COMT) gene variants are involved in different neuropsychiatric disorders and cognitive impairments, associated with altered dopamine function. This study investigated the genotypic and haplotypic association of COMT rs4680 and rs4618 polymorphisms with the severity of cognitive and other clinical symptoms in 544 male and 385 female subjects with schizophrenia. COMT rs4818 G carriers were more frequent in male patients with mild abstract thinking difficulties, compared to CC homozygotes or C allele carriers. Male carriers of COMT rs4680 A allele had worse abstract thinking (N5) scores than GG carriers, whereas AA homozygotes were more frequent in male subjects with lower scores on the intensity of the somatic concern (G1) item, compared to G carriers. Male carriers of COMT rs4818-rs4680 GA haplotype had the highest scores on the G1 item (somatic concern), whereas GG haplotype carriers had the lowest scores on G2 (anxiety) and G6 (depression) items. COMT GG haplotype was less frequent in female patients with severe disturbance of volition (G13 item) compared to the group with mild symptoms, while CG haplotype was more frequent in female patients with severe then mild symptoms. These findings suggest the sex-specific genotypic and haplotypic association of COMT variants with a severity of cognitive and other clinical symptoms of schizophrenia.

People with mental defects are more likely to get the infection due to their low levels of health care and personal hygiene. The current study aimed to determine the seroprevalence of Toxoplasma infection among individuals with intellectual disabilities in Hormozgan province, southern Iran.

The study population was 117 individuals with intellectual disabilities. Venous blood (3 mL) was taken from each subject. A commercial ELISA kit was used to determine anti-Toxoplasma IgG antibodies.

Of 117 recruited subjects, 55 (47.0%) were men and 62 (53.0%) were women. The mean age of participants was 27.6 (±12.31) years. Out of 117 studied subjects, 76 had severe and 41 had profound intellectual disabilities. Anti-Toxoplasma IgG antibodies were detected in the sera of 35 out of 117 (29.9%) individuals. Seropositivity to toxoplasmosis was significantly higher in severe than in individuals with profound intellectual disabilities (P < 0.05). There was no statistically significant association between Toxoplasma infection and age, sex and duration of residency in the rehabilitation centre.

The findings of this study indicate that the prevalence of Toxoplasma in people with intellectual disabilities is not much different from other groups of the community.

Social interaction difficulties are a hallmark of psychotic disorders, which in some cases can be definitely traced back to autoimmunological causes. Interestingly, systemic and intrathecal inflammation have been shown to significantly influence social processing by increasing sensitivity to threatening social stimuli, which bears some resemblance to psychosis. In this article, we review evidence for the involvement of systemic and intrathecal inflammatory processes in psychotic disorders and how this might help to explain some of the social impairments associated with this group of disorders. Vice versa, we also discuss evidence for the immunomodulatory function of social interactions and their potential role for therapeutic interventions in psychotic disorders.

Cultural innovations, such as tools and other technical articles useful for survival, imply that creativity is an outcome of evolution. However, the existence of purely ornamental items obfuscates the functional value of creativity. What is the functional or adaptive value of aesthetic and intellectual ornaments? Recent evidence shows a connection between ornamental creativity, an individual's attractiveness, and their reproductive success. However, this association is not sufficient for establishing that creativity in humans evolved by sexual selection. In this critical review, we synthesize findings from many disciplines about the mechanisms, ontogeny, phylogeny, and the function of creativity in sexual selection. Existing research indicates that creativity has the characteristics expected of a trait evolved by sexual selection: genetic basis, sexual dimorphism, wider variety in males, influence of sex hormones, dysfunctional expressions, an advantage in mating in humans and other animals, and psychological modules adapted to mating contexts. Future studies should investigate mixed findings in the existing literature, such as creativity not being found particularly attractive in a non-WEIRD society. Moreover, we identified remaining knowledge gaps and recommend that further research should be undertaken in the following areas: sexual and reproductive correlates of creativity in non-WEIRD societies, relationship between androgens, development, and creative expression, as well as the impact of ornamental, technical and everyday creativity on attractiveness. Evolutionary research should analyze whether being an evolved signal of genetic quality is the only way in which creativity becomes sexually selected and therefore passed on from generation to generation. This review has gone a long way toward integrating and enhancing our understanding of ornamental creativity as a possible sexual selected psychological trait.