LAUSR

Schizophrenia is a chronic psychiatric disorderwith a heterogeneous studied the effects of betaine supplementation in inbred B6N and genetic and neurobiological background that impacts early brain development and is expressed as a combination of psychotic symptoms — such as hallucinations, delusions and disorganization — and motivational and cognitive dysfunctions [1]. The mean lifetime prevalence of the disorder is just below 1%. The first episode of schizophrenia (FESZ) typically occurs in the late teenage years or the early 20s and early diagnosis and treatment may prevent social disability later. At the time of these first psychotic symptoms, neurobiological processes underlying schizophrenia have already been ongoing for many years. The identification of key pathophysiological pathways to the clinical picture of FESZ is needed if we aim to intervene before thewindow of opportunity is closed and deviations in the brain have become hard-wired [2]. In an article in EBioMedicine, Ohnishi and colleagues demonstrate for the first time that betaine metabolism pathway is involved in psychiatric pathophysiology and the betaine potential as a novel psychotherapeutic [3]. This article is a translational approach based on exciting results obtained by Koike et al. [4]. They used capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to demonstrate altered levels of betaine from peripheral blood samples of patients with a FESZ. Ohnishi and colleagues use a variety of state-of-the-art translational approaches to analyze betaine metabolic pathways on both mouse and human experimental models [3]. They focused on Choline Dehydrogenase (CHDH) enzyme that is involved in betaine biosynthesis. They first generated Chdh-knockout mice in order to analyze transcriptomic changes in the frontal cortex that is known to be involved in schizophrenia pathophysiology. They also studied CHDH variant, rs35518479 that was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression using postmortem brains from schizophrenia patients. Because coexistent betaine pathology and elevated carbonyl stress were evident in a subset of schizophrenia cases, they also generated glyoxylase 1 (GLO1)-deficient human induced Pluripotent Stem Cell (hiPSC) lines by harnessing the CRISPR-Cas9 system. They also