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.

Background: Neurobiology of schizophrenia involves impairment of glutamatergic neurotransmission. In this context, polymorphism in glutamate Ionotropic receptor a-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) type subunit 1 encoded by Glutamate Ionotropic Receptor AMPA Type Subunit 1 Gene (GRIA), (rs1127386, G/A) can be considered as a substantial contributor in pathogenesis of schizophrenia. Therefore, a pilot study was planned to find out if the single nucleotide polymorphism of GRIA (rs1127386, G/A) is a risk factor for schizophrenia in the population of Pakistan. It maps at 5q33, a schizophrenia susceptible locus as per genome-wide association studies. Methodology: Following Diagnostic and Statistical Manual 5 (DSM 5) criteria guidelines, 50 schizophrenia cases were incorporated in this case-control study and 51 controls, individuals without any psychiatric illness. The sternness of illness was figured out using positive and negative syndrome scale score (PANSS) score. Genomic DNA was extracted from blood, and further analysis was done on gel electrophoresis after conducting ARMS (amplification refractory mutation system) PCR. Frequencies of reported genotype and allele within both groups were determined using the chi-square test. Results: Statistically significant difference was not found in genotype and allele frequencies of (rs1127386, G/A) (p>0.05) between cases and controls in the study population. The severity status of the disease was also independent of the polymorphism (p>0.05). Conclusion: This pilot study specifies that polymorphism rs1127386 is not a risk factor for schizophrenia, at least in the Pakistani population.