Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics.

Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics. Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters. Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 µmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 µmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 µmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients' group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls. Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.

Potential role of amino acids in pathogenesis of schizophrenia.

Schizophrenia is a syndrome of inconclusive etiopathogenesis with a prevalence of about 1% in general population. Underlying factors include genetic predisposition and defected neurodevelopment in early stages of life. The role of amino acids has been indicated in some reports. However, very few workers have detailed the effect of each amino acid in the pathophysiology of schizophrenia. Thus, in the present review, we aimed to provide an insight into the potential role of amino acids levels during schizophrenia. Any single amino acid defect cannot lead to the development of the disease. Higher concentration of glycine, serine, glutamate, homocysteine, and arginine are reported by many scientists in blood samples of patients of schizophrenia. Levels of rest of the amino acids show inconsistent results. Involvement of glutamate in pathophysiology of schizophrenia was hypothesized as early as the 1980s. It was demonstrated that dissociative anesthetics which are N-methyl-D-aspartate (NMDA) receptor antagonists can produce all negative, psychotic, cognitive, and physiological features of schizophrenia in healthy controls. This led to the development of hypothesis of NMDA receptor hypofunctioning in the pathophysiology of schizophrenia. Later on, it was also found that agents enhancing functioning of NMDA receptor at glycine modulatory site, improved symptoms in patients of schizophrenia receiving antipsychotic medications. Thus, the relationship of perturb amino acid levels with the biological basis and pathophysiology of schizophrenia is an important area to be further explored for effective management of schizophrenic patients.

1, 25-dihydroxyvitamin D3, a potential role player in the development of thyroid disorders in schizophrenics.

OBJECTIVE: The present study was designed to assess the role of vitamin-D, in the development of autoimmune thyroid dysfunction in newly diagnosed schizophrenics. METHODS: For the present study 100 patients and 100 controls were screened out and studied for their thyroid antibodies, GSH, homocysteine, NOS and vitamin D levels by appropriate protocols to assess the underlying mechanism involved in the schizophrenics susceptible to autoimmune thyroid diseases. RESULTS: The results of the present study depicted that in schizophrenics, levels of cytokines like IL-6 (7.98±0.67 pg/ml), TNF-α, (40.76±6.98 pg/ml), homocysteine (16.98±1.09 µmol/L), Tg-Ab (30.93±3.87 IU/L), TPO-Ab (10.33±1.78 IU/L) and TSHr-Ab (3.76±0.055 IU/L) increased whereas, those of Vit-D (12.76±0.99 pmol/L), NOS (5.99±0.87 IU/L), GSH (4.48±.965 µg/dl) and NO (16.87±3.98 ng/ml) were decreased in the patients as compared to healthy control subjects. CONCLUSION: Vitamin-D in schizophrenia is involved in augmentation of hyperhomocysteinemia, inflammation, oxidative stress and thyroid antibodies, thereby playing a significant role not only in induction of schizophrenic symptoms but may also result in autoimmune thyroid diseases. Thus, earlier detection and rectification of its levels are helpful to limit the miseries of schizophrenia.