Association of Serum Cortisol and Dehydroepiandrosterone Sulfate level with Schizophrenia: A case control study
Abstract
Schizophrenia is a neuro endocrinal diseases purticularly in volving Hypothalamicpituitary-adrenal axis dysfunction, which has been widely researched in schizophrenia. Over activation of this axis is known to cause altered blood levels of cortisol and dehydroepiandrosterone sulfate (DHEA-S). Present study was conducted with the objective to compare serum levels of cortisol and dehydroepiandrosterone sulfate in schizophrenia patients and healthy control. A cross sectional case control observational study was conducted including 40 patients with first-episode schizophrenia along with 40 age and sex matched healthy controls. Patients were diagnosed as Schizophrenia according to ICD-10. Serum cortisol and DHEA-S were assessed in both groups. It was observed in this study that mean Serum level of DHEA-S was significantly (p< 0.001) higher in the Schizophrenia group (4320 ± 1120 µg/dL) as compared to control group (2760 ± 825 µg/dL), while cortisol level did not differ significantly between the two groups. It can be concluded from this study that the first-episode antipsychotic-naïve schizophrenic patients showed a significantly higher blood level of DHEA-S compared with healthy controls indicating role of DHEA-S in patho-physiology of schizophrenia
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Introduction
Schizophrenia is a neuro- endocrino- developmental disorder with complex etiology characterized by interactions between genetic and environmental factors that impact sensitive periods of brain development.1,2 The neuro-endocrinological system, particularly the hypothalamic-pituitary-adrenal axis (HPA) axis, which has been a focus of interest for neurobiological studies aiming at elucidating the cause of schizophrenia. The biological response to stress is mediated through the hypothalamic– pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS), which invoke a number of adaptive behavioral and physiological changes.3 In response to stressors, neural signals are converted into an endocrine response at the level of the hypothalamus leading to activation of the pituitary gland and finally release of corticosteroids by the adrenal gland. Cortisol and Dehydroepiandrosterone sulfate (DHEA-S) are the two major circulating neuro-steroids in the human body which have their effect on brain. Cortisol exerts widespread actions on Central nervous system ranging from regulation of gene transcription, cellular signaling, modulation of synaptic structure and neurotoxicity. On the other hand, dehydroepiandrosterone (DHEA) and its Sulfated form (DHEA-S) are the major circulating neurosteroids which has neuroprotective,4,5 antioxidant6 and anti-inflammatory7 effects on brain. It is considered both a neurosteroid, being produced in the brain, as well as neuroactive steroid, produced in the adrenals and having its effect on the brain. DHEA has potent anti-glucocorticoid actions on the brain and can protect hippocampal neurons from glucocorticoid-induced neuro-toxicity.8
Conclusion
It can be concluded from this present study that patients with first-episode schizophrenia have significantly higher levels of the serum DHEA-S compared to healthy controls. It can be speculated that this measure may serve as a biological adaptive mechanism which antagonizes the neuronal damage caused by cortisol in hippocampus. This study may add to the existing knowledge about pathophysiology of Schizophrenia and give a direction to research for novel treatment strategies also. However, the complex interaction between neuro-steroids, dopamine pathways and neurotransmitters in brain warrant further investigation.