L-kynurenine (KYN), a kynurenine pathway (KP) metabolite, is the main precursor for the neuroactive metabolite kynurenic acid (KYNA). Several studies suggest a patho-physiologically relevant association between increased brain KYNA levels and cognitive dysfunctions in individuals with schizophrenia. Δ9-tetrahydrocannabinol (Δ9-THC; i.e. the main psychoactive compound of cannabis) can worse schizophrenia-related psychosis, often leads to the development of cannabis use disorder in individuals with schizophrenia, and increases the risk of earlier onset of schizophrenia symptoms in those with a genetic predisposition. A role of KP alterations and, specifically, increased brain KYNA levels in Δ9-THC-induced psychotic symptoms has been previously proposed. The aim of the study was to investigate on the possible involvement of KP alterations in Δ9-THC-induced sensorimotor and "tetrad" responses in mice.

Adult male CD-1 mice were treated with Δ9-THC (30 mg/ kg; i.p.) and KYN (20 mg/kg; i.p.), alone or in combination, and body temperature, acute mechanical and thermal analgesia, motor activity and sensorimotor responses were evaluated. Furthermore, brain KYNA levels as well as plasma Δ9-THC and its metabolites concentrations after the treatments were also evaluated.

Brain KYNA levels were significantly increased 1 h, but not 4 h, after KYN and KYN + Δ9-THC administration. KYN administration amplified the Δ9-THC-induced impairment of sensorimotor responses (visual placing, acoustic and tactile responses). Furthermore, KYN significantly increased Δ9-THC-induced motor activity impairment (bar test, drag test and rotarod test) and hypothermia (core and surface body temperature), but not Δ9-THC-induced analgesia. Finally, 1 h after Δ9-THC administration, Δ9-THC and its psychoactive metabolite 11-OH-THC plasma levels were higher in mice pretreated with KYN than in control mice.

The present data indicate for the first time that KYN amplifies the THC-induced sensorimotor impairment and classic "tetrad" response possibly through a pharmacokinetic interaction.

All current drug treatments for epilepsy, a neurological disorder affecting more than 50 million people, merely treat symptoms, and a third of patients with epilepsy do not respond to medication. There are no disease-modifying treatments that may be administered briefly to patients to enduringly eliminate spontaneous seizures and reverse cognitive deficits. Applying network approaches to whole tissue and single-nucleus transcriptomic data collected from mouse models of temporal lobe epilepsy and publicly available transcriptomic data from human temporal lobectomy samples, we confirmed a previously described pattern of rapid and transient induction of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway within days of epileptogenic insult. This was followed by a resurgent activation of the JAK/STAT pathway weeks to months later with the onset of spontaneous seizures. Targeting the first wave of JAK/STAT activation after epileptic insult did not prevent seizures. However, inhibition of the second wave with CP690550 (tofacitinib) over a 2-week period enduringly suppressed seizures, rescued deficits in spatial memory, and alleviated epilepsy-associated histopathological alterations. Seizure suppression lasted for at least 2 months after the final dose. These results indicate that reignition of inflammatory JAK/STAT3 signaling in chronic epilepsy opens a window for disease modification with the US Food and Drug Administration-approved, orally available drug CP690550.

Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia. ApoE-/- mice immunized with SFT2D2-peptides can be used as a model for testing immunotherapy in this subgroup of patients. We used the atypical antipsychotic drug clozapine and immunosuppressant rapamycin to test their effects in this mouse model.

The mice were evaluated for cognitive and schizophrenia-like behaviors. Following behavioral testing, brain samples were collected for analyzing specific pathological changes and dendritic spine formation.

Clozapine and rapamycin reversed impaired pre-pulse inhibition, motor impairment, and improved cognitive ability in ApoE -/- mice exposed to anti-SFT2D2 immunoglobulin G. Immunohistochemical assays revealed that both clozapine and rapamycin significantly reduced activated microglial infiltration and restored neuronal dendritic spine density.

Our study results suggested that clozapine and rapamycin possess therapeutic benefits for managing autoimmune psychosis and provide mechanistic insights into immunotherapies involving immunosuppressive agents.

There is an urgent need for mechanistically novel and more efficacious treatments for schizophrenia, especially those targeting negative and cognitive symptoms with a more favorable side-effect profile. Drug repurposing-the process of identifying new therapeutic uses for already approved compounds-offers a promising approach to overcoming the lengthy, costly, and high-risk process of traditional CNS drug discovery. This review aims to update our previous findings on the clinical drug repurposing pipeline in schizophrenia. We examined studies conducted between 2018 and 2024, identifying 61 trials evaluating 40 unique repurposed drug candidates. These encompassed a broad range of pharmacological mechanisms, including immunomodulation, cognitive enhancement, and hormonal, metabolic, and neurotransmitter modulation. A notable development is the combination of the muscarinic modulators xanomeline, a compound with antipsychotic properties, and trospium, included to mitigate peripheral side effects, now approved by the FDA as the first antipsychotic drug in decades with a fundamentally novel mechanism of action. Moving beyond the traditional dopaminergic paradigm of schizophrenia, such findings highlight opportunities to improve treatment-resistant symptoms and alleviate adverse effects. Overall, the evolving drug repurposing landscape illustrates a significant shift in the rationale for schizophrenia drug development, highlighting the potential of in silico strategies, biomarker-based patient stratification, and personalized treatments that align with underlying pathophysiological processes.

Due to its intricacy and long-term usefulness, traditional medicine continues to be practiced in several nations. Among the many medicinal plants found in the Dhofar region of Oman, the aromatic oleo-gum resin generated by Boswellia sacra, commonly referred to as frankincense, stands out for its medical and commercial significance. Resin-carrying ducts are unique to members of the Boswellia family. Boswellia sacra Flueck is one of the 29 species in the genus Boswellia (Burseraceae) and has long been cultivated for its aromatic gums and resins for use as incense. In addition to the resins (60%-80% alcohol soluble), gums (15%-20% water soluble), and essential oil (5%-7%), other components, including polysaccharides and polymeric compounds, also exist in smaller amounts. Physiochemical analyses indicate that Boswellia resin oil is made up of 42.5% diterpenes, 13.1% monoterpenes, and 1% sesquiterpenes. Traditional medicine makes extensive use of frankincense for the treatment of stomach diseases, Alzheimer's disease, and hepatic illnesses. The bioactive chemicals present in frankincense, particularly boswellic acids, are plentiful. The current review examines various compounds present in different species of Boswellia, especially Boswellia sacra, along with their structure.

The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behavior. Understanding relationships across these scales may be fundamental to advancing understanding of brain function in health and disease. Recent neuroimaging research has shown that functional brain alterations that are associated with schizophrenia spectrum disorders (SSDs) are already present in young adults at clinical high risk for psychosis (CHR-P), but the cellular and molecular determinants of these alterations remain unclear.

Here, we used regional cerebral blood flow (rCBF) data from 425 individuals (122 with an SSD compared with 116 healthy control participants [HCs] and 129 individuals at CHR-P compared with 58 HCs) and applied a novel pipeline to integrate brainwide rCBF case-control maps with publicly available transcriptomic data (17,205 gene maps) and neurotransmitter atlases (19 maps) from 1074 healthy volunteers.

We identified significant correlations between astrocyte, oligodendrocyte, oligodendrocyte precursor cell, and vascular leptomeningeal cell gene modules for both SSD and CHR-P rCBF phenotypes. Additionally, endothelial cell genes were correlated in SSD, and microglia in CHR-P. Receptor distribution significantly predicted case-control rCBF differences, with dominance analysis highlighting dopamine (D1, D2, dopamine transporter), acetylcholine (VAChT, M1), gamma-aminobutyric acid A (GABAA), and glutamate (NMDA) receptors as key predictors for SSD (R2adjusted = 0.58, false discovery rate [FDR]-corrected p < .05) and CHR-P (R2adjusted = 0.6, pFDR < .05) rCBF phenotypes. These associations were primarily localized in subcortical regions and implicate cell types involved in stress response and inflammation, alongside specific neuroreceptor systems, in shared and distinct rCBF phenotypes in psychosis.

Our findings underscore the value of integrating multiscale data as a promising hypothesis-generating approach toward decoding biological pathways involved in neuroimaging-based psychosis phenotypes, potentially guiding novel interventions.

Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in this disorder has been verified, the impact of long noncoding RNAs (lncRNAs) associated with this pathway has not been studied in schizophrenia. The objective of this study was to examine the expression levels of Wnt/β-catenin-related lncRNAs, namely CCAT2, SNHG5, PTCSC3, and DANCR, as well as the CTNNB1 gene encoding beta-catenin protein in two groups of schizophrenia patients (drug-naïve and medicated) compared with healthy individuals. This study included 50 medicated patients in the remission phase of the disease, 25 drug-naive patients in the acute phase, and 50 control subjects. There was no significant difference in CTNNB1 gene expression in the medicated patients compared to controls (P value = 0.9754). However, the expression of this gene was significantly decreased in drug-naïve first-episode patients compared with controls (P value < 0.001). In contrast, expression of DANCR, PTCSC3, SNHG5, and CCAT2 genes was significantly higher in medicated (P values < 0.001, < 0.001, = 0.01, < 0.001, respectively) and drug-naive first-episode patients (P value < 0.001) compared to control subjects. ROC curve analysis revealed that DANCR, PTCSC3, SNHG5, and CCAT2 genes had diagnostic power with specificity and sensitivity of 80% and above in separation between study subgroups. In brief, our data demonstrated dysregulation of Wnt/β pathway related genes and lncRNAs in the peripheral blood of patients with schizophrenia and their potential as biomarkers for this disorder.

Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42). Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19). N-acetylcysteine improved negative symptoms (SMD = -0.90, 95%CI = -1.42; -0.39)/general psychopathology (SMD = -0.76, 95%CI = -1.39; -0.13). No compound improved total symptomatology within acute phase studies (k = 7, n = 422). Sarcosine (SMD = -1.26,95%CI = -1.91; -0.60), citicoline (SMD = -1.05,95%CI = -1.65;-0.44), and N-acetylcysteine (SMD = -0.55,95%CI = -0.92,-0.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD = -1.10, 95%CI = -1.75,-0.45), L-lysine (SMD = -1.05,95%CI = -1.55, -0.19), omega-3 fatty acids (SMD = -0.83,95%CI = -1.31, -0.34) and withania somnifera (SMD = -0.71,95%CI = -1.21,-0.22). Citicoline (SMD = -1.05,95%CI = -1.86,-0.23), L-lysine (SMD = -1.04,95%CI = -1.84,-0.24), N-acetylcysteine (SMD = -0.89,95%CI = -1.35,-0.43) and sarcosine (SMD = -0.61,95%CI = -1.02,-0.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.

Schizophrenia is a complex mental disorder influenced by genetic and environmental factors, including dietary habits. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Emerging research suggests that diet may affect schizophrenia through different biological mechanisms beyond oxidative stress and inflammation. In particular, epigenetic changes may alter the expression of genes related to neurodevelopment and neurotransmitter systems, while neuroplasticity plays a crucial role in brain adaptation and resilience to psychiatric disorders.

The literature search included the main available databases (Science Direct, PubMed and Google Scholar), considering the English language, and our screening was performed based on several words such as "schizophrenia", "diet", "nutrients", "obesity", "oxidative stress", "inflammation", "antioxidants" and "prenatal nutritional deficiency". The review focused specifically on studies examining the relevance of diet in schizophrenia, as well as prenatal nutritional deficiency, obesity, oxidative stress, and inflammation associated with this disorder.

Following a review of the literature, it was found that nutritional deficiencies, including lack of omega-3 fatty acids, vitamins D, and B, during the prenatal and postnatal periods can have a negative impact on neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia have imbalances in antioxidant enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and reduced levels of antioxidants (vitamin E, vitamin C). These biochemical changes lead to an increase in markers of oxidative stress, including malondialdehyde (MDA). In addition, cytokine-mediated inflammation, microglial activation, and intestinal dysbiosis are associated with the onset of schizophrenia and the severity of schizophrenia symptoms. Currently, there is no universally accepted dietary regimen for control. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the overall health of patients, including the Mediterranean diet, the ketogenic diet, the gluten-free diet, and the DASH (Dietary Approaches to Stop Hypertension) diet.

A healthy diet, rich in anti-inflammatory nutrients and antioxidants, may help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D, and B vitamins are particularly important for brain development and function. In this review, we aim to analyze the literature on the influence of diet on schizophrenia, focusing on the role of prenatal nutritional deficiencies, obesity, oxidative stress, and inflammation.

The causal relationships between sexually transmitted infections, depression, and self-harm remain unclear.

We executed various Mendelian Randomization (MR) analyses. At the same time, a cross-sectional analysis from NHANES was used for verification and an enrichment analysis was also utilized to explore the potential common gene functions.

We found that STIs may have a potential causal effect on depression (P = 0.002) and self-harm (P = 0.003). Conversely, self-harm has been identified as a risk factor for the acquisition of STIs (P = 0.006), while there is no evidence to support an effect of depression on STIs. Furthermore, mediation MR indicated that monocyte absolute count played a mediating role in the association between STIs and depression, accounting for 7.7%. And then, the weighted regression analysis of the cross-sectional analysis demonstrated a significant association between one of the common STIs, HPV, and depression. Gene enrichment analysis suggested that the PI3K-Akt signalling pathway and the infectious virus signalling pathway may represent a common underlying pathogenesis.

STIs may increase the risk of depression and self-harm, while self-harm might also represent a risk factor for STIs, which could provide insights and a foundation for the control of STIs and mental health monitoring in clinical practice.

Schizophrenia (SCZ) is a complex psychotic syndrome whose pathogenesis involves countless protagonists, none of which, to date, can fully explain how this disorder develops. In this narrative review, an overview of the biochemical impairment is offered according to several perspectives. Indeed, the metabolic framework behind SCZ dopaminergic hypotheses, glutamate - gamma-amynobutyric acid dysregulation, norepinephrine and serotonin, calcium channel dysfunction is addressed together with the energetic impairment, involving glucose and lipids in SCZ etiopathogenesis, in order to highlight the multilevel pathways affected in this neuropsychiatric disorder. Furthermore, neuroinflammation is analyzed, by virtue of its important role, widely investigated in recent years, in neurodegeneration. Tracing the neurotransmitter activity at the brain level by assessing the metabolic network behind the abovementioned molecules puts into light as unavoidable the need for future studies to adopt an integrate approach to address SCZ pathological and clinical picture. The combination of all these factors, essential in acquiring an overview on the complexity of SCZ pathophysiology represents a crucial step in the development of a more targeted management of SCZ patients.

Schizophrenia is a disabling mental disorder that affects 1% of people over their lifetime. The etiology and mechanism of schizophrenia are very complex, and many genes are involved in many different signaling pathways in the etiology of this disease. According to recent studies, one of the important mechanisms altered in this disorder is the regulation of immune system and the inflammation mechanism. In the present study, we evaluated the peripheral blood expression pattern of four lncRNAs and three protein-coding genes in the treatment- naïve patients, and medicated patients compared with sex and age-matched controls. In the medicated-patients, expression levels of IFNG, IL18RAP, AC007278.2 were significantly up-regulated (P < 0.05); and the expression level of IFNG-AS1-001 was significantly down-regulated compared to healthy controls (P < 0.05). However, levels of IL18R1, AC007278.3 and IFNG-AS1-003 were not different between these groups. In the treatment-naïve patients, IFNG, IL18R1, IL18RAP, IFNG-AS1-001, AC007278.2, and AC007278.3 were significantly up-regulated compared to controls. On the other hand, IFNG-AS1-003 was significantly down-regulated in the treatment-naïve patients compared to controls. Based on the Spearman correlation matrix, there was a significant correlation between genes in the treatment-naïve patients. We also showed the high sensitivity and specificity of IFNG-AS1-003, IFNG, IL18R1, and AC007278.3 in the identification of treatment-naïve patients from controls. The current study contributes further evidence to the understanding of the role of lncRNAs in the pathogenesis of schizophrenia. Future research is necessary to establish the validity of lncRNAs as peripheral markers for this condition.

This review article explores the transformative potential of dynamic, real-time biosensing in biorhythm tracking for psychiatric disorders. Psychiatric diseases, characterized by a complex, heterogeneous, and multifactorial pathophysiology, pose challenges in both diagnosis and treatment. Common denominators in the pathophysiology of psychiatric diseases include disruptions in the stress response, sleep-wake cycle, energy metabolism, and immune response: all of these are characterized by a strong biorhythmic regulation (e.g., circadian), leading to dynamic changes in the levels of biomarkers involved. Technological and practical limitations have hindered the analysis of such dynamic processes to date. The integration of biosensors marks a paradigm shift in psychiatric research. These advanced technologies enable multiplex, non-invasive, and near-continuous analysis of biorhythmic biomarkers in real time, overcoming the constraints of conventional approaches. Focusing on the regulation of the stress response, sleep/wake cycle, energy metabolism, and immune response, biosensing allows for a deeper understanding of the heterogeneous and multifactorial pathophysiology of psychiatric diseases. The potential applications of nanobiosensing in biorhythm tracking, however, extend beyond observation. Continuous monitoring of biomarkers can provide a foundation for personalized medicine in Psychiatry, and allow for the transition from syndromal diagnostic entities to pathophysiology-based psychiatric diagnoses. This evolution promises enhanced disease tracking, early relapse prediction, and tailored disease management and treatment strategies. As non-invasive biosensing continues to advance, its integration into biorhythm tracking holds promise not only to unravel the intricate etiology of psychiatric disorders but also for ushering in a new era of precision medicine, ultimately improving the outcomes and quality of life for individuals grappling with these challenging conditions.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Magnesium (Mg) has attracted considerable attention as a biodegradable material for medical implants owing to its excellent biocompatibility, mitigating long-term toxicity and stress shielding. Nevertheless, challenges arise from its rapid degradation and low corrosion resistance under physiological conditions. To overcome these challenges, titanium (biocompatibility and corrosion resistance) has been integrated into Mg. The incorporation of titanium significantly improves mechanical and corrosion resistance properties, thereby enhancing performance in biological settings. Mg-Ti alloys are produced through mechanical alloying and spark plasma sintering (SPS). The SPS technique transforms powder mixtures into bulk materials while preserving structural integrity, resulting in enhanced corrosion resistance, particularly Mg80-Ti20 alloy in simulated body fluids. Moreover, Mg-Ti alloy revealed no more toxicity when assessed on pre-osteoblastic cells. Furthermore, the ability of Mg-Ti-based alloy to create composites with polymers such as PLGA (polylactic-co-glycolic acid) widen their biomedical applications by regulating degradation and ensuring pH stability. These alloys promote temporary orthopaedic implants, offering initial load-bearing capacity during the healing process of fractures without requiring a second surgery for removal. To address scalability constraints, further research is necessary to investigate additional consolidation methods beyond SPS. It is essential to evaluate the relationship between corrosion and mechanical loading to confirm their adequacy in physiological environments. This review article highlights the importance of mechanical characterization and corrosion evaluation of Mg-Ti alloys, reinforcing their applicability in fracture fixation and various biomedical implants.

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

In people with schizophrenia (PwS), inflammation and metabolic issues significantly increase morbidity and mortality. However, our ability to understand inflammatory-metabolic mechanisms in this population has been limited to cross-sectional studies. This study involved 169 PwS and 156 non-psychiatric comparisons (NCs), aged 25-65, observed between 2012 and 2022 with 0 to 5 follow-ups post-baseline. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, was measured via a particle-enhanced immuno-turbidimetric assay. Body mass index (BMI) was used as a proxy for metabolic function. The measurement intervals for hs-CRP and BMI ranged between 6 and 48 months. Linear mixed models (LMM) results revealed that at all time points, PwS has a higher hs-CRP (t (316) = 4.73, p < .001) and BMI (t (315) = 4.13, p < .001) than NCs; however, for BMI, this difference decreased over time (t (524) = -5.15, p < .001). To study interrelationships between hs-CRP and BMI, continuous time structural equational modeling (CTSEM) was used, accounting for uneven measurement intervals. CTSEM results showed that both hs-CRP predicted future BMI (Est. = 12.91, 95 % CI [7.70; 17.88]) and BMI predicted future hs-CRP (Est. = 1.54, 95 % CI [1.00; 2.04]), indicating a bidirectional relationship between inflammation and metabolic function. Notably, the influence of hs-CRP on future BMI was more robust than the other lagged relationship (p = .015), especially in PwS (Est. = 2.43, 95 % CI [0.39; 0.97]). Our study highlights the important role of inflammation in metabolic function and offers insights into potential interventions targeting inflammation in PwS.

Schizophrenia is one of the most disabling psychiatric disorders characterized by positive (hallucinations, delusions, formal thinking disorder) and negative symptoms (anhedonia, lack of speech and motivation). The present study aimed to identify the predictive factors of schizophrenia in adults, and potential differences in the environment of origin, sex, levels of occupational stress, intellectual level, marital status and age of onset of the disease depending on the severity of symptoms using analysis of data collected from 120 patients with a diagnosis of schizophrenia. The study was conducted at the 'Prof. Dr. Alexandru Obregia' Clinical Psychiatric Hospital in Bucharest and included adult patients hospitalized between March 2018 and January 2021 diagnosed with schizophrenia and evaluated by general clinical examination, psychiatric, neurological and psychological evaluation. Results revealed that robust predictors of mild and moderate symptoms were affective symptoms, heredo-collateral history of schizophrenia, late onset, the presence of positive and negative symptoms, substance abuse, stress and marital status, unmarried, lower IQ and mental deficiency. For moderate-severe and severe symptoms, predictors were affective symptoms, heredo-collateral history of schizophrenia and affective disorders, substance abuse, stress, borderline IQ and mild mental deficiency. The present results can be used for further development of psychopharmacological management of schizophrenia.

Brain development/aging is not uniform across individuals, spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or aging map onto specific symptom facets.

Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms.

ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity.

Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.

The recent pandemic caused by the SARS-CoV-2 virus and the associated mental health complications have renewed scholarly interest in the relationship between viral infections and the development of mental illnesses, a topic that was extensively discussed in the previous century in the context of other viruses, such as influenza. The most probable and analyzable mechanism through which viruses influence the onset of mental illnesses is the inflammation they provoke. Both infections and mental illnesses share a common characteristic: an imbalance in inflammatory factors. In this study, we sought to analyze and compare cytokine profiles in individuals infected with viruses and those suffering from mental illnesses. The objective was to determine whether specific viral diseases can increase the risk of specific mental disorders and whether this risk can be predicted based on the cytokine profile of the viral disease. To this end, we reviewed existing literature, constructed cytokine profiles for various mental and viral diseases, and conducted comparative analyses. The collected data indicate that the risk of developing a specific mental illness cannot be determined solely based on cytokine profiles. However, it was observed that the combination of IL-8 and IL-10 is frequently associated with psychotic symptoms. Therefore, to assess the risk of mental disorders in infected patients, it is imperative to consider the type of virus, the mental complications commonly associated with it, the predominant cytokines to evaluate the risk of psychotic symptoms, and additional patient-specific risk factors.

Young people who are at clinical high-risk for psychosis experience suicidal thoughts and behaviors at a greater rate than young people in the general population. However, no suicide prevention interventions have been specifically designed for or tested with this group of young people. To address this gap, we need to identify and leverage malleable potential intervention targets that can be measured at multiple levels of analysis. Here, we argue that social network structure, or the pattern of relationships in which a person is embedded, offers one potential target for intervention. We first provide a select review of what is currently known about social network structure and suicide risk, social network disruption among people at clinical high-risk for psychosis, and inflammatory processes as a potential underlying metric of social bond disruption. We then propose opportunities to advance suicide prevention research focused on young people at clinical high-risk for psychosis, with an eye toward establishing a foundation for future interventions that can account for biological, psychological, and social domains.

Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.

Schizophrenia is a disease with a complex etiology that significantly impairs the functioning of patients. In recent years, there has been increasing focus on the importance of the gut microbiota in the context of the gut-brain axis. In our study, we analyzed data on the gut-brain axis in relation to schizophrenia, as well as the impacts of eating habits, the use of various supplements, and diets on schizophrenia. Additionally, the study investigated the impact of antipsychotics on the development of metabolic disorders, such as diabetes, dyslipidemia, and obesity. There may be significant clinical benefits to be gained from therapies supported by supplements such as omega-3 fatty acids, B vitamins, and probiotics. The results suggest the need for a holistic approach to the treatment of schizophrenia, incorporating both drug therapy and dietary interventions.

The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.

Evidence suggests that inflammatory processes play a role in the pathophysiology of schizophrenia. Statins exert anti-inflammatory and antioxidant effects and may be effective in improving the symptoms of schizophrenia. This study explored whether statins, as an adjunctive therapy, can alleviate the symptoms of schizophrenia.

PubMed, EMBASE, and the Cochrane Library were searched for articles published up to March 2023. The risk-of-bias tool for randomized trials was used to assess study quality. Two researchers independently assessed the risks of bias and extracted data. Pooled data on Positive and Negative Syndrome Scale (PANSS) scores were analyzed. A random-effects model was employed to calculate pooled effect sizes. Statistical heterogeneity across studies was assessed using the I2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software.

Nine trials enrolling 533 patients in total were included. Add-on statin therapy was found to be associated with a significantly better total PANSS score [standardized mean difference (SMD) = -0.42, 95% confidence interval (CI) -0.75 to -0.09, I2 = 72%; P = 0.01] and PANSS negative subscale score (SMD = -0.26, 95% CI -0.45 to -0.07, I2 = 0%; P = 0.009) in comparison with placebo. However, add-on statin therapy did not appear to improve scores for the PANSS positive and general subscales at the study-defined endpoint (6-24 weeks).

Our meta-analysis indicates that adjunctive statin therapy may confer benefits in ameliorating PANSS negative and total scores. It needs more solid data to confirm the results are related to clinical improvement and functioning.

Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS).

To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.

We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS).

Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026).

Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls.

The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models.

The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls.

In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These disorders include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorders, headaches, and epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted the role of immunity and neuroinflammation in neuropsychiatric disorders. Toll-like receptors (TLRs) are innate receptors that act as a bridge between the innate and adaptive immune systems via adaptor proteins (e.g., MYD88) and downstream elements; TLRs are classified into 13 families that are involved in normal function and illnesses of the CNS. TLRs expression affects the course of neuropsychiatric disorders, and is influenced during their pharmacotherapy; For example, the expression of multiple TLRs is normalized during the major depressive disorder pharmacotherapy. Here, the role of TLRs in neuroimmunology, treatment, and management of neuropsychiatric disorders is discussed. We recommend longitudinal studies to comparatively assess the cell-type-specific expression of TLRs during treatment, illness progression, and remission. Also, further research should explore molecular insights into TLRs regulation and related pathways.

Observational studies have confirmed that mental illness and pulmonary tuberculosis are closely related and increase each other's incidence; however, whether there is a causal genetic association between the two diseases remains unknown. We attempted to answer this question using bidirectional two-sample Mendelian randomization (MR) in a large cohort study.

We performed a bidirectional MR analysis between mental illness (major depressive, anxiety disorder, bipolar disorder, and schizophrenia) and pulmonary tuberculosis using summary statistics from genome-wide association studies in European individuals. The inverse-variance weighted method was used as the primary analytical method to assess causality. In addition, other additional MR methods (weighted median, MR-Egger, and weighted mode) were used to supplement the inverse-variance weighted results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability.

We identified no causal genetic association between mental illness and pulmonary tuberculosis after applying the inverse variance weighted method (major depressive: odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.59-1.71, P = 0.98; anxiety disorder: OR = 1.72, 95% CI = 0.05-67.67, P = 0.76; bipolar disorder OR = 0.89, 95% CI = 0.66-1.22, P = 0.48; and schizophrenia: OR = 1.05, 95% CI = 0.91-1.20, P = 0.51). Similarly, pulmonary tuberculosis was not caustically associated with mental illness (major depressive: OR = 1.01, 95% CI = 1.00-1.02, P = 0.17; anxiety disorder: OR = 1.00, 95% CI = 0.99-1.01, P = 0.06; bipolar disorder: OR = 1.02, 95% CI = 0.98-1.07, P = 0.38; and schizophrenia: OR = 1.01, 95% CI = 0.97-1.05, P = 0.66).

Our research does not support a bidirectional causal association between the aforementioned mental illnesses and pulmonary tuberculosis.

Inflammation has been related to schizophrenia (SZ). The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker, however, its potential predictive value in patients with SZ has not been extensively investigated. This study aimed to examine whether NLR could predict the clinical response to antipsychotics in this population. One hundred and ninety-five medication-naïve first-episode schizophrenia (MNFES) patients were recruited and received treatment with risperidone for 12 weeks in the present study. Clinical symptoms were evaluated at week 0 and the end of 12 weeks of treatment using the PANSS scales. Complete blood counts were determined at baseline. We found that baseline NEU counts and NLR were positively associated with improvements in clinical symptoms in patients. In addition, MNFES patients with higher baseline NLR values showed a better treatment response to antipsychotics. Linear regression analysis revealed a predictive role of baseline NLR for the improvements of clinical symptoms in SZ patients. Our findings demonstrate that higher NLR was related to better improvements in symptoms after 12 weeks of treatment with antipsychotics, which renders it a promising biomarker of the response to antipsychotics in clinical practice.

The emergence of a new coronavirus strain caused the COVID-19 pandemic. While vaccines effectively control the infection, it's important to acknowledge the potential for side effects, including rare cases like psychosis, which may increase with the rising number of vaccinations.

Our systematic review aimed to examine cases of new-onset psychosis following COVID-19 vaccination.

We conducted a systematic review of case reports and case series on new-onset psychosis following COVID-19 vaccination from December 1st, 2019, to November 21st, 2023, using PubMed, MEDLINE, ClinicalKey, and ScienceDirect. Data extraction covered study and participant characteristics, comorbidities, COVID-19 vaccine details, and clinical features. The Joanna Briggs Institute quality assessment tools were employed for included studies, revealing no significant publication bias.

A total of 21 articles described 24 cases of new-onset psychotic symptoms following COVID-19 vaccination. Of these cases, 54.2% were female, with a mean age of 33.71 ± 12.02 years. Psychiatric events were potentially induced by the mRNA BNT162b2 vaccine in 33.3% of cases, and psychotic symptoms appeared in 25% following the viral vector ChAdOx1 nCoV-19 vaccine. The mean onset time was 5.75 ± 8.14 days, mostly reported after the first or second dose. The duration of psychotic symptoms ranged between 1 and 2 months with a mean of 52.48 ± 60.07 days. Blood test abnormalities were noted in 50% of cases, mainly mild to moderate leukocytosis and elevated C-reactive protein. Magnetic resonance imaging results were abnormal in 20.8%, often showing fluid-attenuated inversion recovery hyperintensity in the white matter. Treatment included atypical antipsychotics in 83.3% of cases, typical antipsychotics in 37.5%, benzodiazepines in 50%, 20.8% received steroids, and 25% were prescribed antiepileptic medications. Overall, 50% of patients achieved full recovery.

Studies on psychiatric side effects post-COVID-19 vaccination are limited, and making conclusions on vaccine advantages or disadvantages is challenging. Vaccination is generally safe, but data suggest a potential link between young age, mRNA, and viral vector vaccines with new-onset psychosis within 7 days post-vaccination. Collecting data on vaccine-related psychiatric effects is crucial for prevention, and an algorithm for monitoring and treating mental health reactions post-vaccination is necessary for comprehensive management.

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023446270.

Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

Electroconvulsive therapy (ECT) is an effective treatment modality for schizophrenia. However, its antipsychotic-like mechanism remains unclear.

To gain insight into the antipsychotic-like actions of ECT, this study investigated how repeated treatments of electroconvulsive seizure (ECS), an animal model for ECT, affect the behavioral and transcriptomic profile of a neurodevelopmental animal model of schizophrenia.

Two injections of MK-801 or saline were administered to rats on postnatal day 7 (PN7), and either repeated ECS treatments (E10X) or sham shock was conducted daily from PN50 to PN59. Ultimately, the rats were divided into vehicle/sham (V/S), MK-801/sham (M/S), vehicle/ECS (V/E), and MK-801/ECS (M/E) groups. On PN59, prepulse inhibition and locomotor activity were tested. Prefrontal cortex transcriptomes were analyzed with mRNA sequencing and network and pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) analyses were subsequently conducted.

Prepulse inhibition deficit was induced by MK-801 and normalized by E10X. In M/S vs. M/E model, Egr1, Mmp9, and S100a6 were identified as center genes, and interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF) signaling pathways were identified as the three most relevant pathways. In the V/E vs. V/S model, mitophagy, NF-κB, and receptor for advanced glycation end products (RAGE) pathways were identified. qPCR analyses demonstrated that Igfbp6, Btf3, Cox6a2, and H2az1 were downregulated in M/S and upregulated in M/E.

E10X reverses the behavioral changes induced by MK-801 and produces transcriptional changes in inflammatory, insulin, and mitophagy pathways, which provide mechanistic insight into the antipsychotic-like mechanism of ECT.

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.

Novel antidepressants are predominantly evaluated preclinically in rodent models of chronic stress in which animals experience a single prolonged exposure to chronic stress prior to treatment. Rodent models of a single episode of chronic stress translate poorly to human depressive disorders, which are commonly marked by recurring depressive episodes. Intravenous administration of Reelin has previously been shown to resolve immobility in the forced swim test of rats exposed to a single prolonged exposure to chronic stress. To determine whether Reelin has antidepressant-like properties in a model of recurring depressive episodes, Long-Evans rats (N = 57) were exposed to multiple cycles of chronic stress and stress-free periods before the administration of a single injection of Reelin during the final cycle of chronic stress. The animals then performed in the forced swim test and open field test before the post-mortem evaluation of Reelin cell counts in the sub-granular zone of the dentate gyrus to determine the impact of treatment on hippocampal Reelin levels and spleen white pulp to evaluate the role of Reelin treatment in peripheral inflammation. The results show a single Reelin injection reversed elevated levels of immobility in the forced swim test in both male and female subjects exposed to the cyclic chronic stress model of recurring depressive episodes. Treatment with Reelin also restored Reelin-positive cell counts in the dentate gyrus sub-granular zone and reversed atrophy of spleen white pulp. The results shown here indicate that treatment with Reelin could effectively resolve alterations in forced swim test behavior caused by the cyclic corticosterone model of recurring depressive episodes and that Reelin homeostasis is important for regulating stress-related inflammation. Future preclinical antidepressant research should incorporate models of multiple depressive episodes to improve the translation of preclinical rodent research to human depressive disorders.

Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear. This study aimed to develop a pipeline based on bioinformatics and systems biology approaches for identifying potential therapeutic targets involving possible biological mechanisms from SZ patients and healthy volunteers. About 420 overlapping differentially expressed genes (DEGs) from three RNA-seq datasets were identified. Gene ontology (GO), and pathways analysis showed several biological mechanisms enriched by the commonly shared DEGs, including extracellular matrix organization (ECM) organization, collagen fibril organization, integrin signaling pathway, inflammation mediated by chemokines and cytokines signaling pathway, and GABA-B receptor II and IL4 mediated signaling. Besides, 15 hub genes (FN1, COL1A1, COL3A1, COL1A2, COL5A1, COL2A1, COL6A2, COL6A3, MMP2, THBS1, DCN, LUM, HLA-A, HLA-C, and FBN1) were discovered by comprehensive analysis, which was mainly involved in the ECM organization and inflammatory signaling pathway. Furthermore, the miRNA target of the hub genes was analyzed with the random-forest-based approach software miRTarBase. In addition, the transcriptional factors and protein kinases regulating overlapping DEGs in SZ, namely, SUZ12, EZH2, TRIM28, TP53, EGR1, CSNK2A1, GSK3B, CDK1, and MAPK14, were also identified. The results point to a new understanding that the hub genes (fibronectin 1, collagen, matrix metalloproteinase-2, and lumican) in the ECM organization and inflammatory signaling pathways may be involved in the SZ occurrence and pathogenesis.

Innate immunity has been shown to be associated with schizophrenia (Sch). This study explored the relationship between symptoms and neutrophil-to-lymphocyte ratio (NLR) (a marker of innate immunity) in patients with Sch. Ninety-seven first-episode medication-naïve (FEMN) patients with Sch and 65 healthy controls were recruited in this study. We measured the complete blood count and assessed the clinical symptoms using the PANSS scales. We found higher NEU counts and NLR in patients with Sch compared with control subjects. Male patients showed a higher NEU count than female patients. In addition, FEMN patients with higher NLR and NEU values showed higher PANSS-p, PANSS-g, and PANSS-total scores (all p < 0.05). Regression analysis revealed that NLR was a predictor for PANSS total scores in patients with Sch. Higher NLR value was observed in patients with Sch and the significant associations between NLR and psychotic symptoms indicate that an imbalance in inflammation and innate immune system may be involved in the pathophysiology of Sch.