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.