The rs1986112 Variant is Associated with Increased RAB8B Gene Expression in Schizophrenic Patients.

BACKGROUND: Schizophrenia (SCZ) is a serious mental disorder that interferes with a person's cognitive processes and leads to social disability. A wide range of factors may play important roles in increased risk of SCZ development. Genetic contributors are among the most influential actors involved in different molecular mechanisms leading to the development of the nervous system, thus they play pivotal roles in psychotic disorders and SCZ de-velopment. RAB8B is characterized for its key roles in several cellular and molecular mechanisms which are linked with different psychotic disorders, such as SCZ. METHODS: In this study, we assessed the expression level of RAB8B gene in blood samples of schizophrenic patients and normal healthy controls by means of quantitative real time PCR. We also investigated the correlation between RAB8B-rs1986112 genotypes and RAB8B expression levels through SNP genotyping by means of the PCR-RFLP method. RESULTS: Our results indicated a significant difference of RAB8B mRNA ratio between SCZ patients and healthy controls. Moreover, we showed significant upregulation of RAB8B in patients with rs1986112 GG and AG genotype compared to AA genotype. CONCLUSIONS: Our findings suggest a role for RAB8B and its regulatory variation, rs1986112 in SCZ development.

Support for "Disease-Only" Genotypes and Excess of Homozygosity at the CYTH4 Primate-Specific GTTT-Repeat in Schizophrenia.

OBJECTIVE: The role of short tandem repeats (STRs) in the control of gene expression among species is being increasingly understood following the identification of several instances in which certain STRs occur identically, or expand differentially, in primates versus nonprimates. These STRs may regulate genes that participate in characteristics that are associated with the divergence of primates from sibling orders (e.g., brain higher order functions). The CYTH4 gene contains the longest tetranucleotide STR in its core promoter, at 7-repeats, and links to the evolution of human and nonhuman primates. Allele and genotype distribution of this STR were studied in patients affected by schizophrenia (SCZ) and controls. METHODS: High-resolution data were obtained on the allele and genotype distribution of the CYTH4 STR and a novel C > T single-nucleotide polymorphism (SNP) at its immediate upstream sequence in 255 patients with SCZ and 249 controls. Each sample was sequenced twice using the fluorescent dye termination method. RESULTS: Novel alleles were detected at the long extreme of the GTTT-repeat, at 10- and 11-repeats, in the SCZ cases and controls. Excess of homozygosity was observed for the entire range of alleles across the GTTT-repeat and the C > T SNP in the SCZ patients in comparison with the controls (Yates corrected p < 0.011). Three genotypes consisting of the 11-repeat allele (i.e., 11/11, 10/11, and 7/11) were detected only in the SCZ patients (i.e., disease-only genotypes), and contributed to 2.3% of the SCZ genotypes (Mid p exact <0.007). The frequency of the 11-repeat allele was estimated at 0.02 and 0.006 in the SCZ patients and controls, respectively (Mid p exact <0.006). CONCLUSION: This indicates that STR genotypes that are absent in the control group may be risk factors for SCZ. Future studies are warranted to test the significance of our findings.

Association of ß-Secretase Functional Polymorphism with Risk of Schizophrenia.

AIM: The NRG1-ERBB4 neurotransmitter signaling pathway plays a key role in the pathogenesis of schizophrenia (SZ). The intronic single-nucleotide polymorphism rs707284 in ERBB4 links to PI3K-AKT suppression in SZ. Another protein indirectly affecting NRG1-ERBB4 signaling is ß-secretase, which is encoded by the BACE1 gene, and activates NRG1 by proteolytic cleavage. In this study, we aimed to investigate the association of ERBB4 rs707284 and BACE1 rs490460 with the risk of SZ in an Iranian population. SUBJECTS AND METHODS: A total of 973 subjects, including 480 SZ patients and 493 healthy controls, matched by ethnicity, age, and gender, were recruited in a case-control study. Genomic DNA was extracted from peripheral blood of all subjects and genotyping of rs707284 and rs490460 was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system (tetra-ARMS) PCR genotyping assays, respectively. RESULTS: A significant association was observed between the rs490460 T allele and SZ (p = 0.0002, odds ratio 0.69, 95% confidence interval 0.57-0.84). There was no association between the risk of SZ and rs707284. CONCLUSION: Our data indicate that rs490460 is associated with the risk of SZ. In silico analysis indicates that rs490460 may be a potential splicing site, which affects protein structure. Replication studies are needed to confirm our data.

Parental self-efficacy as a determining factor in healthy mother-child interaction: a pilot study in iran.

OBJECTIVE: Parental self-efficacy is associated with increasing mental health in children. There is a paucity of research in Iran on the role of parental self-efficacy in increasing mental health status of children. In this preliminary study, we studied the effectiveness of the World Health Organization international child development program (2002) for children aged 3 years and younger in increasing positive interaction between child and mother as an important component of mental health. METHODS: Forty mothers from a central hospital child-caring center in Mashhad participated in the study and were randomly divided into an experimental group (n = 20) and a control group (n = 20). The experimental group received the World Health Organization international child development program for 6 consecutive weeks while the control group remained without manipulation. The Parenting Self-Agency Measure (PSAM) was administered at pre-test, post-test and at 1-month follow-up. RESULTS: The study findings indicated that parental efficacy in the experimental group increased after 6 consecutive weeks of training and remained unchanged after 1 month of follow-up while the control group showed no difference regarding scores obtained at three stages of the study. CONCLUSION: International programs such as the World Health Organization international child development program can increase positive child-mother interaction as an important factor which contributes to mental health in early years of life but further studies with larger samples in longer terms and with more follow-up periods in Iran are suggested. DECLARATION OF INTEREST: None. Clinical Trial Registration-URL: http://www.irct.ir. Unique identifier: IRCT2012073010445N1.

Nonmedical abuse of benzodiazepines in opiate-dependent patients in tehran, iran.

OBJECTIVE: The purpose of the present preliminary study was to explore the prevalence of nonmedical abuse of benzodiazepines in a group of opiate-dependent patients who were on methadone maintenance treatment (MMT) program in outpatient clinics in the south-west of Tehran, Iran. METHODS: 114 male and female opiate-dependent clients who met DSM.IV-TR criteria for opiate dependence with mean age 36.5 years participated in the study from 16 clinics and completed a self-report questionnaire on demographics and substance use details. Then the participants were interviewed on the details of nonmedical abuse of benzodiazepines. RESULTS: The study findings indicated that the current nonmedical abuse of benzodiazepines was commonly prevalent among participants. The most common current benzodiazepines abused were alprazolam (100%) followed by chlordiazepoxide (96.5%), clonazepam (94.7%), diazepam (86.8%), lorazepam (79.8%) and oxazepam (73.7%) respectively. Depression (77%) and anxiety (72.8%) were frequently reported as the most important reasons associated with consuming benzodiazepines followed by problem in anger control (44.7%), suicide thought (12.3%), self-injury (7.9%), and suicide commitment (5.3%) respectively. CONCLUSION: Nonmedical abuse of benzodiazepines is an important problem among opiate addicts which should be considered in treatment interventions during MMT program.