[Show abstract][Hide abstract] ABSTRACT: Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear.
Behavioral and Brain Functions 10/2014; 10(1):35. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
The present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naïve, first episode schizophrenia.
Drug naïve, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer.
Forty-six patients with drug naïve, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p = 0.013, p < 0.001, p = 0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps > 0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r = 0.327, p = 0.026; r = 0.338, p = 0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r = 0.319, p = 0.031; r = 0.321, p = 0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r = 0.312, p = 0.035). Controlling for potential confounding variables resulted in similar findings.
Drug naïve, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia.
Schizophrenia Research 10/2014; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was to examine cortical thickness in drug naïve, first episode schizophrenia patients, and to explore its relationship with serum levels of brain-derived neurotrophic factor (BDNF). Forty-five drug naive schizophrenia patients and 28 healthy controls were enrolled in the study. Freesurfer was used to parcellate cortical regions, and vertex-wise group analysis was used for whole brain cortical thickness. The clusters for the brain regions that demonstrated group differences were extracted, and the mean values of thickness were calculated. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay (ELISA). After controlling for age and gender, significantly thinner cortical thickness was found in left insula and superior temporal gyrus in the patient group compared with the healthy control group (HC group) (p's < 0.001). Lower serum levels of BDNF were also found in the patient group compared with the HC group (p = 0.001). Correlation analysis showed a significant positive relationship between thickness of left insula and serum levels of BDNF within the HC group (r = 0.396, p = 0.037) but there was no such relationship within the patient group (r = 0.035, p = 0.819). Cortical thinning is present in drug naïve, first episode schizophrenia patients, indicating neurodevelopmental abnormalities at the onset of schizophrenia. Left insula might be an imaging biomarker in detecting the impaired protective role of neurotrophic factor for the brain development in schizophrenia.
Journal of Psychiatric Research 09/2014; · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.
The World Journal of Biological Psychiatry 06/2014; · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the change in plasma protein expression in first episode schizophrenia after an 8-week treatment with risperidone, and to explore potential biomarkers for metabolic side effects associated with risperidone treatment. Eighty first-episode schizophrenia patientswere enrolled in the study. Fifteen of the 80 patients were randomly selected to undergo proteomic analysis. Plasma proteins were obtained before and after the 8-week risperidone treatment, and measured using two-dimensional gel electrophoresis (2-DE), Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF/TOF) and peptide mass fingerprinting.Proteins with the highest fold changes after risperidone treatment were then measured for all 80 patients using enzyme linked immunosorbent assay (ELISA). The relationship between changes in plasma protein levels and changes in metabolic parameters after risperidone treatment was examined. In 15 randomly selected patients, approximately 1,500 protein spots were detected in each gel by 2-DE. Of those proteins, 22 spots showed significant difference in abundance after risperidone treatment (p's<0.05). After MALDI-TOF peptide mass fingerprinting, apolipoprotein A-I (APOA-I) and Guanine Nucleotide Binding Protein, Alpha Stimulating (GNAS), were found to have the highest fold changes.The content of APOA-I was significantly increased, and the content of GNAS was significantly decreased after risperidone treatment (p's<0.05). The analysis in the entire study sample showed similar findings in changes of APOA-I and GNAS after risperidone treatment. Further analysis showed significant relationships between changesin APOA-1 and changes in triglyceride, total cholesterol, and body mass index after controlling for age, gender and family history of diabetes. Similar analysis showed a trend positive relationship between changes in GNAS and changes in BMI. Using proteomic analysis, the study suggested that APOA-I might be a novel biomarkers related to metabolic side effects in first episode schizophrenia treated with risperidone.
PLoS ONE 04/2014; 9(4):e93902. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study was to examine the role of pro-inflammatory T helper 17 (Th17) cells in drug naïve, first episode schizophrenia.
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 4 weeks of risperidone treatment.
Sixty-nine patients with normal weight, drug naïve, first episode schizophrenia and 60 healthy controls were enrolled. At baseline, the patient group had 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 4 weeks of risperidone treatment, the proportion of Th17 cells decreased significantly (p<0.001), there was a significant positive relationship between the PANSS total score change rate and the change in proportion of Th17 cells (p=0.039).
Patients with normal weight, drug naïve, first episode schizophrenia present activation of Th17 cells, which might be associated with therapeutic response after risperidone treatment.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2014; · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: MicroRNA137 (miRNA137) regulates several gene expressions involved in brain development, and a recent large genome wide association study (GWAS) revealed a possible association between miRNA137 and schizophrenia. Methods: The allelic variants of rs66642155, a variable number tandem repeat polymorphism, and the single nucleotide polymorphism rs1625579 A/C in the miRNA137 host gene fragment were compared between 300 schizophrenic patients and 300 healthy controls from the Han Chinese population. The association of these polymorphisms with clinical characteristics of schizophrenia was also tested. Results: Genotype and allele frequencies of these polymorphisms were not significantly different between patient and control populations. In patients, however, age at onset was much later in wild type rs66642155 carriers than in mutation carriers. Total positive score on the Positive and Negative Symptom Scale (PANSS), total five-factor model positive score, and the delusions symptom score were all significantly higher in wild type rs66642155 carriers with schizophrenia, while the disturbance of volition symptom score was significantly higher in the mutation carriers with schizophrenia. Conclusions:MiRNA137 may not be a significant susceptibility gene for schizophrenia, but in patients, rs66642155 allelic variant of miRNA137 appears to influence age at onset and the severity of positive symptoms.
The International Journal of Psychiatry in Medicine 01/2014; 47(2):153-168. · 0.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case-control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI: 1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ(2)=0.07, P=0.795), and the difference in pooled ORs between ancestries was not significant (Z=0.25, P=0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.
Schizophrenia Research 12/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to examine the changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia.
Sixty-two drug naïve, first-episode schizophrenia (SZ group) and 60 healthy individuals (control group) were enrolled in the study. Serum interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and body weight were measured at baseline for both groups, and repeated for the SZ group at five different time points during 6-month risperidone treatment.
At baseline, serum IL-1β, IL-6, and TNF-α levels in the SZ group (53.28 ± 12.62, 33.98 ± 14.13, 50.08 ± 12.86 pg/mL, respectively) were significantly higher than those in the control group (23.49 ± 15.27, 15.53 ± 7.16, 32.12 ± 15.23 pg/mL, respectively) (p's < 0.001). Within the SZ group, serum IL-1β levels decreased significantly at 2 weeks (48.02 ± 16.00 pg/mL, p < 0.01) and 1 month (44.70 ± 16.63 pg/mL, p < 0.001), but then gradually increased at 2 months (48.49 ± 18.87 pg/mL), 3 months (50.59 ± 18.48 pg/mL) and 6 months (53.64 ± 16.22 pg/mL) to the levels comparable to baseline; serum IL-6 levels changed significantly over the course of treatment (p = 0.001), but reached the levels comparable to baseline at 6 months (37.13 ± 13.23 pg/mL); serum levels of TNF-α increased significantly at 3 months (55.02 ± 16.69 pg/mL, p < 0.01) and 6 months (58.69 ± 13.57 pg/mL, p < 0.001); steady and significant weight gain was observed at each follow-up time point (p's < 0.001), from 56.71 ± 9.25 kg at baseline to 62.72 ± 9.53 kg at 6 months.
Risperidone treatment is associated with changes in serum pro-inflammatory cytokines levels and weight. There is an initial anti-inflammatory effect that reduces with treatment, potentially due to its weight gain side effect.
[Show abstract][Hide abstract] ABSTRACT: The study was to examine the levels of adiponectin (APN) and other cytokines, and body metabolism in drug naïve, first episode schizophrenia patients with normal weight.
Ninety-six drug naïve, first episode schizophrenia patients with normal weight (SZ group), 60 healthy individuals with normal weight (control group), and 60 overweight or obese but otherwise healthy individuals (obesity group) were enrolled in the study. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and APN were measured using enzyme linked immunosorbent assay (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels were measured using the enzymatic colorimetric method.
Serum levels of IL-1β, IL-6 and TNF-α in both the SZ group and the obesity group were significantly higher than those in the control group (p's<0.001). There were no significant differences between the SZ group and the obesity group on those cytokines (p's>0.05). In addition, the levels of APN were significantly higher in the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01) compared with the control group. Further, there were significant positive relationships between levels of APN and levels of other cytokines within the SZ group (p's<0.05); in contrast, there were significant negative relationships between levels of APN and levels of other cytokines within the obesity group (p's<0.05). Fasting serum levels of glucose, LDL, triglycerides and total cholesterol were significantly higher, and fasting serum levels of HDL were significantly lower in the obesity group compared with the other two groups (p's<0.01). There were no significant differences in any of the metabolic parameters between the control group and the SZ group (p's>0.05).
Drug naïve, first episode schizophrenia patients with normal weight seem to present an up-regulated inflammatory status as reflected by elevated levels of IL-1β, IL-6, and TNF-α. APN may play a unique pro-inflammatory role in this patient population. Implications of the findings in relation to the pathogenesis of schizophrenia and the vulnerability for metabolic problems were discussed.
Schizophrenia Research 08/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 factors analysis of the positive and negative syndrome scale (PANSS) scores of first episode SZ patients, mean negative factor score (F2,249 =3.986, p=0.02) and depression/anxiety factor score (F2, 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.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2013; · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myosin Vb (MYO5B) has recently been implicated in the etiology of bipolar disorder in a genome-wide association study (GWAS). This gene is involved in amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) recycling and plays an important role in the primary excitatory neurotransmission. Dysfunction of the brain glutamate system has been postulated to be involved in the pathophysiology in schizophrenia. To further investigate the association between MYO5B polymorphisms and schizophrenia, we genotyped nine single nucleotide polymorphisms (SNPs) in an independent sample of 1463 individuals with schizophrenia and 1563 healthy control subjects, and detected three SNPs and two haplotype blocks which displayed significant association with schizophrenia. This association was further strengthened by the results of meta-analysis. Our data strongly supported that the MYO5B gene might be associated with schizophrenia in the Chinese Han population and they have implications for understanding the glutamate hypothesis of schizophrenia.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Estrogen is believed to play an important role in the central nervous system (CNS) and exert a protective role against schizophrenia. Estrogen receptor alpha (ESRalpha) mediates the biological action of estrogen. Rs2234693 and rs9340799, single nucleotide polymorphisms of ESRalpha, may be related to many psychiatric disorders, while their association with schizophrenia has not been clarified. METHODS: Genotypes rs2234693 and rs9340799 were detected in 303 schizophrenic patients and 292 healthy controls in a Chinese population. The positive and negative syndrome scale (PANSS) was used to estimate symptoms and therapeutic effects. The association of these polymorphisms with schizophrenia and clinical characteristics was analyzed by the chi-square test, analysis of variance, and others. RESULTS: The distribution of genotypes and allele frequencies of rs2234693 and rs9340799 exhibited no significant differences between patients and controls, while haplotypes consisting of these polymorphisms had significant differences. For 2234693, T-allele carriers had an earlier age at onset. CC-homozygote carriers had a higher general psychopathology score and its percentage reduction in male and paranoid patients, respectively. CC-homozygote carriers had a higher tension (G4) and poor impulse control (G14) score, mainly in paranoid patients. Furthermore, patients with the CC homozygote had higher reductions of G4 and G14 scores when treated by aripirazole and risperidone, respectively. CONCLUSIONS: Haplotypes consisting of these two polymorphisms in ESRalpha may be strongly associated with schizophrenia. The rs2234693 was related to age at onset, general psychopathology, G4 and G14 symptoms, even the therapeutic effect in different groups.
Behavioral and Brain Functions 03/2013; 9(1):12. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent researches have implicated that mutations in the neurexin-3 (NRXN3) gene on chromosome 14q24.3-q31.1 might play a role in addiction, autism, and obesity. In order to explore the association of NRXN3 polymorphisms with schizophrenia, we examined seven single nucleotide polymorphisms (SNPs) in NRXN3 spanning 1.33Mb of this gene, in a Chinese Han sample of 1,214 schizophrenic patients and 1,517 healthy control subjects. Our results showed that three SNPs were associated with schizophrenia (rs7157669: A>C, p=0.006; rs724373: C>T, p=0.014; rs7154021: C>T, p=0.018). After corrected for multiple tests, the association of rs7157669 remained significant but those for two others were modest. According to the linkage disequilibrium pattern, the 7 SNPs may construct 3 haplotype blocks. Several haplotypes were significantly associated with schizophrenia, constructed by rs11624704-rs7157669- rs724373 (AAC, p=0.003; ACT, p=0.007, both remained significant after permutation tests), rs7154021-rs7142344 (TT, p=0.024; CT, p=0.012), respectively. Among the patients, 326 ones at first onset have received 6-week monotherapy of risperidone. Further analyses showed that two SNPs were associated with percentage of bodyweight gain following a 6-week therapy of risperidone (rs11624704: p=0.03; rs7154021: p=0.008) and rs7154021 remained significant after permutation test. Our findings suggested that NRXN3 might represent a major susceptibility gene for schizophrenia and have a role in bodyweight gain related to therapy of risperidone in Chinese Han population.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2013; · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent genome wide association studies (GWASs) assessing the relationship between schizophrenia (SZ) and the ZNF804A gene, particularly the single nucleotide polymorphism (SNP) rs1344706, have yielded conflicting results. Schizophrenia is a heterogeneous disorder, so it is possible that an association may be restricted to specific SZ subtypes and that population heterogeneity may obscure a contribution of ZNF804A allelic variation to SZ risk. We thus evaluated the association between rs1344706 and different clinical SZ subtypes in a large Han Chinese patient population.
The rs1344706 genotype was determined in 1,025 SZ patients and 977 healthy controls using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLPs). The clinical SZ subtypes included paranoid, catatonic, disintegrated, and undifferentiated, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition IV (DSM-IV).
No significant differences in genotype and allele frequencies were found between controls and either the total SZ population (A > C, chi2 = 4.339, 2.994; p = 0.227, 0.087, respectively) or paranoid SZ patients (chi2 = 2.053, 0.002; p = 0.562, 0.973, respectively). However, there was a significant association between genotype frequency and SZ subtype (chi2 = 12.632, p = 0.049).
We found no evidence that the ZNF804A SNP rs1344706 is a susceptibility locus for SZ. However, conflicting results from previous association studies may be due to genetic heterogeneity between different patient SZ subtypes.
The International Journal of Psychiatry in Medicine 01/2013; 45(3):269-78. · 0.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response.
Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects.
There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05).
These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.
Behavioral and Brain Functions 02/2012; 8:11. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia.
We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests.
PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring.
Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.
Behavioral and Brain Functions 12/2011; 7:50. · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study genotyped four SNPs (rs736707, rs2229864, rs362691, and rs2073559) of the Reelin gene (RELN) in 165 autistic trios, 67 sporadic autistic children and 283 healthy controls with Chinese Han pedigree. Both case-control analysis and transmission disequilibrium test (TDT) found no evidence of significant association. The results do not support previous positive findings and suggest that the four single-nucleotide polymorphisms (SNP) of RELN are unlikely to be associated with childhood autism in Chinese Han population.
Psychiatry Research 05/2011; 187(3):462-4. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia (SZ) is a common and complex psychiatric disorder with a strong genetic component. Previous research suggests that mutations altering genes in neurodevelopmental pathways contribute to SZ. Reelin gene (RELN) maps to chromosome 7q22.1, the encoded protein plays a pivotal role in guiding neuronal migration, lamination and connection during embryonic brain development. Several reports had indicated that reduced RELN expression is associated with human mental illnesses such as SZ, mood disorders and autism. In this study, case-control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ. Thirty-seven single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was found between rs12705169 and SZ (p=0.001). Moreover, the haplotypes constructed from five SNPs showed significant differences between cases and controls (p=0.041). When subjects were divided by gender, rs12705169 remained significant difference only in females (OR=0.24, 95%CI=0.14-0.40 for CC and OR=0.40, 95%CI=0.27-0.58 for AC), both in the allele and genotype (p=0.0001 for both). This study describes a positive association between RELN and SZ in the Han Chinese population, and provides genetic evidence to support the gender difference of SZ.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2011; 35(6):1505-11. · 4.03 Impact Factor