Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

Impact of Brain derived Neurotrophic factor gene polymorphism on its peripheral levels in schizophrenic patients.

Objectives: To determine serum levels of brain-derived neurotrophic factor and its polymorphism rs12291063 in schizophrenic patients. METHODS: The case-control study was conducted from January1, 2020, to May 15, 2021, at Dr Abdul Qadeer Khan Institute of Behavioural Sciences, Dow University of Health Sciences, Karachi, and comprised schizophrenia cases aged 14-60 years who were diagnosed using Diagnostic and Statistical Manual of Mental Disorders-V criteria, and healthy controls without any psychiatric illness. Positive and negative syndrome scale score was used to assess disease severity. The genomic deoxyribonucleic acid of the subjects was isolated from peripheral blood, followed by polymerase chain reaction, gel electrophoresis and sequencing of the amplicons. The sequences were analysed using MEGA X software for genotyping. Serum brain-derived neurotrophic factor levels were assessed using enzyme-linked immunosorbent assay. Data was analysed using SPSS 21. RESULTS: Of the 100 subjects, 50(50%) were cases; 36(72%) males and 14(28%) females (p<0.05) with mean age 34.34±10.32 years. There were 50(50%) controls; 32(64%) males and 18(36%) females (p=0.391) with mean age 30.886±8.88 years. Among the cases, the mean age at schizophrenia diagnosis was 25.14±9.54 years, and there was a significant association with positive family history for psychiatric disorders (p<0.05). Sequencing revealed no T>C substitution. Serum brain-derived neurotrophic factor levels were significantly higher in cases compared to controls (p<0.001). There was a weak negative correlation between brain-derived neurotrophic factor levels and positive and negative syndrome scale score (p<0.05). CONCLUSIONS: Higher brain-derived neurotrophic factor levels were found to be associated with schizophrenia, while no association of rs12291063 T>C was found with schizophrenia.

Diclofenac sodium enhances the antiepileptic effect of levetiracetam in pilocarpine induced epileptic mice model.

Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.

Synonymous polymorphism rs201256011 in dopamine receptor type 2 gene is associated with schizophrenia and PANSS score in Pakistani population: A first report.

AIM: Variations of dopamine receptor type 2 (DRD2) are among the key factors involved in the pathology of schizophrenia. Presence of certain SNPs in DRD2 gene also amend patients' response to antipsychotics. Keeping in view the genetic diversity among populations and important role of DRD2 polymorphisms in schizophrenia, we aimed to study two of its SNPs rs1801028 and rs6277 in patients with schizophrenia from Pakistan. METHODS: A total of 100 schizophrenia cases and 100 healthy controls were recruited. DNA was extracted from whole blood followed by PCR, Sanger sequencing and genotyping of two SNPs, that is, rs1801028 and rs6277. RESULTS: No association of rs1801028 and rs6277 was found with schizophrenia in Pakistani population (P > .05). Highlight of our study is the association of polymorphism rs201256011 with schizophrenia (P = .001), which is being reported for the first time. Significant association of rs201256011 was also found with Positive and Negative Syndrome Scale negative, cognitive and total score (P < .05). CONCLUSION: In conclusion, genetic variants rs1801028 and rs6277 of DRD2 are not associated with schizophrenia in Pakistani population. While, previously unreported polymorphism rs201256011 have shown significant association with schizophrenia and its severity. A large scale multicentre replication study is required to confirm the association of this SNP with schizophrenia.

Patterns of musculoskeletal disorders in health care providers and their association with ergonomic risks.

Objectives. Musculoskeletal disorders (MSDs) have a high prevalence among allied health care providers because of the demanding nature of their work and lack of practicing proper ergonomics. The aim of this study focused on patterns of work-related musculoskeletal disorders (WMSDs) affecting different health care providers working in a different unit of a tertiary care hospital. Methods. This cross-sectional study collected data from 2000 allied health care providers working at various departments of Civil Hospital and Dow University Hospital of Karachi (DUHS), via self-administered questionnaire, based on Occupational Safety and Health Administration (OSHA) guidelines. Results. Our findings revealed that 92.9% of individuals had MSDs as a result of poor ergonomics, with 93% reporting that the disease interferes with their normal job routine. Conclusions. Medical technologists are the most affected group among allied health care workers. Lack of knowledge and improper ergonomic culture results in such a high prevalence rate in allied health care workers in Pakistan.

A Novel Variant in Dopamine Receptor Type 2 Gene is Associated with Schizophrenia.

BACKGROUND: Being the primary target of antipsychotic therapy, dopamine receptor type 2 (DRD2) remains a point of interest in schizophrenia pathology. Polymorphisms in DRD2 have been shown to alter patients' response to antipsychotics. DRD2 SNP rs6275 (C>T) have found to be associated with schizophrenia in different populations; however, data remains inconsistent. AIM OF THE STUDY: Keeping in view the genetic diversity the present study was aimed to explore association of rs6275 with schizophrenia in population from Pakistan. METHOD: Using Diagnostic and statistical Manual 5 (DSM 5) criteria, 100 schizophrenia cases and 100 controls (individuals without any psychiatric illness) were enrolled in the study. Severity of illness was determined using PANSS score. Genotyping was done via Sanger sequencing. MEGA-X was used to align the sequences, Expasy translate tool was used to translate nucleotide sequences. Difference in genotype and allele frequencies between cases and controls was determined using χ2 test. RESULT: No significant difference in genotype or allele frequencies of rs6275 (p >0.0.5) was found between cases and controls. Interestingly, a novel SNP (C>A, Pro297Thr) was spotted during electropherogram analysis at position chr11:113412805. Significant difference was found in genotype and allele frequency of this novel SNP among schizophrenia cases and controls (p = 0.003). CONCLUSION: No association of rs6275 was observed with schizophrenia in Pakistani population. However, the study found significant association of a novel missense SNP of DRD2 at chr11:113412805 (C>T) with schizophrenia in Pakistani population. A large-scale multicenter study will be required to confirm the association of this novel SNP with schizophrenia.