Glutathione Depletion and Concomitant Elevation of Susceptibility in Patients with Parkinson's Disease: State-of-the-Art MR Spectroscopy and Neuropsychological Study.

Parkinson's disease (PD) is characterized by extrapyramidal motor disturbances and nonmotor cognitive impairments which impact activities of daily living. Although the etiology of PD is still obscure, autopsy reports suggest that oxidative stress (OS) is one of the important factors in the pathophysiology of PD. In the current study, we have investigated the impact of OS in PD by measuring the antioxidant glutathione (GSH) levels from the substantia nigra (SN), left hippocampus (LH) and neurotransmitter γ-amino butyric acid (GABA) levels from SN region. Concomitant quantitative susceptibility mapping (QSM) from SN and LH was also acquired from thirty-eight PD patients and 30 age-matched healthy controls (HC). Glutathione levels in the SN region decreased significantly and susceptibility increased significantly in PD compared to HC. Nonsignificant depletion of GABA was observed in the SN region. GSH levels in the LH region were depleted significantly, but LH susceptibility did not alter in the PD cohort compared to HC. Neuropsychological and physical assessment demonstrated significant impairment of cognitive functioning in PD patients compared to HC. GSH depletion was negatively correlated to motor function performance. Multivariate receiver operating characteristic (ROC) curve analysis on the combined effect of GSH, GABA, and susceptibility in the SN region yielded an improved diagnostic accuracy of 86.1% compared to individual diagnostic accuracy based on GSH (65.8%), GABA (57.5%), and susceptibility (69.6%). This is the first comprehensive report in PD demonstrating significant GSH depletion as well as concomitant iron enhancement in the SN region.

SWADESH: a multimodal multi-disease brain imaging and neuropsychological database and data analytics platform.

Multimodal neuroimaging data of various brain disorders provides valuable information to understand brain function in health and disease. Various neuroimaging-based databases have been developed that mainly consist of volumetric magnetic resonance imaging (MRI) data. We present the comprehensive web-based neuroimaging platform "SWADESH" for hosting multi-disease, multimodal neuroimaging, and neuropsychological data along with analytical pipelines. This novel initiative includes neurochemical and magnetic susceptibility data for healthy and diseased conditions, acquired using MR spectroscopy (MRS) and quantitative susceptibility mapping (QSM) respectively. The SWADESH architecture also provides a neuroimaging database which includes MRI, MRS, functional MRI (fMRI), diffusion weighted imaging (DWI), QSM, neuropsychological data and associated data analysis pipelines. Our final objective is to provide a master database of major brain disease states (neurodegenerative, neuropsychiatric, neurodevelopmental, and others) and to identify characteristic features and biomarkers associated with such disorders.

Schizophrenia, Bipolar and Major Depressive Disorders: Overview of Clinical Features, Neurotransmitter Alterations, Pharmacological Interventions, and Impact of Oxidative Stress in the Disease Process.

Psychiatric disorders are one of the leading causes of disability worldwide and affect the quality of life of both individuals and the society. The current understanding of these disorders points toward receptor dysfunction and neurotransmitter imbalances in the brain. Treatment protocols are hence oriented toward normalizing these imbalances and ameliorating the symptoms. However, recent literature has indicated the possible role of depleted levels of antioxidants like glutathione (GSH) as well as an alteration in the levels of the pro-oxidant, iron in the pathogenesis of major psychiatric diseases, viz., schizophrenia (Sz), bipolar disorder (BD), and major depressive disorder (MDD). This review aims to highlight the involvement of oxidative stress (OS) in these psychiatric disorders. An overview of the clinical features, neurotransmitter abnormalities, and pharmacological treatments concerning these psychiatric disorders has also been presented. Furthermore, it attempts to synthesize literature from existing magnetic resonance spectroscopy (MRS) and quantitative susceptibility mapping (QSM) studies for these disorders, assessing GSH and iron, respectively. This manuscript is a sincere attempt to stimulate research discussion to advance the knowledge base for further understanding of the pathoetiology of Sz, BD, and MDD.