Short overview on metabolomic approach and redox changes in psychiatric disorders

Abstract

Schizophrenia, depression and posttraumatic stress disorder (PTSD) are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment. Metabolomics is a discipline that combines different strategies with the aim to extract, detect, identify and quantify all metabolites that are present in a biological sample and might provide mechanistic insights into the etiology of various psychiatric disorders. Therefore, oxidative stress research combined with metabolomics might offer a novel approach in dissecting psychiatric disorders, since these data-driven but not necessarily hypothesis-driven methods might identify new targets, molecules and pathways responsible for development of schizophrenia, depression or PTSD. Findings from the oxidative research in psychiatry together with metabolomics data might facilitate development of specific and validated prognostic, therapeutic and clinical biomarkers. These methods might reveal bio-signatures of individual patients, leading to individualized treatment approach. In reviewing findings related to oxidative stress and metabolomics in selected psychiatric disorders, we have highlighted how these novel approaches might make a unique contribution to deeper understanding of psychopathological alterations underlying schizophrenia, depression and PTSD.

Alterations of Astrocytes in the Context of Schizophrenic Dementia

“…At the same time, oxidative and nitro stress can be caused by non-inflammatory stimuli (mitochondrial dysfunction, dopamine, hyperhomocysteinemia, smoking, hypofunction of NMDA receptors, etc.) (Leza et al, 2015;Nedic Erjavec et al, 2018). Oxidative stress is observed in the prefrontal cortex, anterior cingulate cortex and hippocampus, which matches with the places of altered astrocyte activity in schizophrenia.…”

“…Oxidative stress inhibits the activity of NMDA receptors, which can lead to the appearance of ketamine-like symptoms, and has inhibitory effects on glycogen metabolism in mice (Lavoie et al, 2011). In this case, free radicals can cross the blood-brain barrier, which becomes more permeable due to the product of lipid peroxidation 4-hydroxynonenal (Nedic Erjavec et al, 2018) and other agents, causing an inflammatory response and a decrease in pH as a result of chronic stress (van Kesteren et al, 2017). However, under the influence of certain circumstances astrocytes can emit molecules, such as sonic hedgehog, which provoke the repair of blood-brain barrier (Sofroniew, 2015) Interneurons are very sensitive to damage from oxidative stress, especially at the beginning of postnatal development (Grace, 2016).…”

“…In this case, microglia mainly produces type 1 cytokines, such as interleukin (IL)-12, and astrocytes inhibit the production of IL-12 and produce type 2 cytokines, for example, IL-10 (van Kesteren et al, 2017). The dysregulation of this balance can damage the neurons, cause a deficit of interneurons, leading to alteration of oligodendrocytes and inhibition of gamma-aminobutyric acid (GABA) interneurons (Nedic Erjavec et al, 2018). IL-1b and IL-6 promoted dopaminergic transmission (Purves-Tyson et al, 2019).…”

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

“…Activation of the Wnt/β-catenin pathway is facilitated by the localization of LRP6 in lipid rafts (Nedic Erjavec et al, 2018).…”

The genomic architecture of blood metabolites based on a decade of genome-wide analyses

“…An improved understanding of the genetic architecture of metabolites will benefit our understanding of the aetiology of diseases and traits, such as cardiometabolic diseases 24 , migraine 25 , psychiatric disorders 26 , and cognition 27 . Here we aim to further our understanding of the contribution of genetic factors to variation in fasting blood metabolic measures (henceforth referred to as metabolites for brevity) by the analysis of data from multiple metabolomics platforms in a large cohort of twins and family members ( N = 5,117).…”