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Objective: The present study was to examine the role of pro-inflammatory T helper 17 (Th17) cells in drug naïve, first episode schizophrenia. Method: Patients with normal weight, drug naïve, first episode schizophrenia and healthy controls were enrolled in the study. Flow cytometric analysis was performed to analyze the proportion of Th17 cells among the CD4+ T cells. Plasma levels of interleukin-17 (IL-17), interferon-γ (IFN-γ) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). All measures were repeated for the patient group after 4weeks of risperidone treatment. Results: Sixty-nine patients with normal weight, drug naïve, first episode schizophrenia and 60 healthy controls were enrolled. At baseline, the patient group hadz significantly higher proportions of Th17 cells and plasma levels of IFN-γ and IL-6 compared with the control group (p's<0.01). Within the patient group, there were significant positive relationships between the proportion of Th17 cells, plasma levels of IL-17, IFN-γ, IL-6 and the PANSS total score after controlling for potential confounding variables (p's<0.05). After 4weeks of risperidone treatment, the proportion of Th17 cells decreased significantly (p<0.001), and there was a significant positive relationship between the PANSS total score change rate and the change in proportion of Th17 cells (p=0.039). Conclusions: Patients with normal weight, drug naïve, first episode schizophrenia present activation of Th17 cells, which might be associated with therapeutic response after risperidone treatment. [ABSTRACT FROM AUTHOR]

Highlights • There was no improvements in PANSS positive, PANSS negative, and PANSS general subscales between the group of Sodium nitroprusside (SNP) and placebo controls. • There was not find any effect of SNP on cognitive function as measured by the Wechsler Adult Intelligence Scale. • The safety of SNP (0.5 µg/kg/min) is an affirmative. • During treatment greater empathy can enhanced compliance and may have reduced adverse events such as anxiety. Abstract Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18–45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 μg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods: One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. Results: One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusions: Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. Trial Registration: chictr.org [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between GRIN2B polymorphisms and SZ susceptibility and symptoms in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a complex psychiatric disorder with a strong genetic component. The serotonin transporter (SERT), encoded by solute carrier family 6 member 4 (SLC6A4), regulates synaptic concentrations of serotonin and thereby strongly influences perception, mood, emotion, behavior, and cognition, all of which are severely disturbed in SZ. Two variable numbers of tandem repeat (VNTR) polymorphisms and several single nucleotide polymorphisms (SNPs) spread throughout SLC6A4 are involved in both neuropsychiatric diseases (including SZ) and personality traits. In this study, case-control association analysis was performed in the Chinese-Han population to identify additional allelic variants of the SLC6A4 gene that may confer susceptibility to SZ. Ten relatively common SNPs (minor allele frequency >5%) were genotyped in 528 paranoid SZ patients and 528 control subjects. Significant associations were found between SZ and the allele and genotypic frequencies of rs140700G/A (p =2.45×10−12, 2.34×10−11, respectively). The frequency of the A allele was lower in SZ patients (17.7%) than in controls (30.9%; OR=1.93, 95%CI=1.58–2.36). In five factor analysis of the positive and negative syndrome scale (PANSS) scores of first episode SZ patients, mean negative factor score (F 2,249 =3.986, p =0.02) and depression/anxiety factor score (F 2, 249 =8.766, p =2.11×10−4) were significantly different among the rs140700G/A genotypes, with both scores higher for genotype AA than AG+GG. The rs140700G/A allele of SLC6A4 is strongly associated with SZ susceptibility and symptom expression in the Chinese-Han population. [ABSTRACT FROM AUTHOR]

• MIA induces progressive worsening behaviors in adolescents and adults offspring. • MIA impaires ERK activation in offspring. • MIA induces age- and region-related alterations of neurofilaments in offspring. Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. Methods: Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague–Dawley rats prenatally challenged with polyriboinosinic–polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1β, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. Results: Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. Conclusions: Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia. [ABSTRACT FROM AUTHOR]