Genetic evidence for a role of the SREBP transcription system and lipid biosynthesis in schizophrenia and antipsychotic treatment.

Vidar M Steen, Silje Skrede, Tatiana Polushina, Miguel López, Ole A Andreassen, Johan Fernø, Stephanie Le Hellard

Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 2018;27(6):589-598

PMID: 27492885

Full Text on Elsevier Science View on PubMed

Abstract

Schizophrenia is a serious psychotic disorder, with disabling symptoms and markedly reduced life expectancy. The onset is usually in late adolescence or early adulthood, which in time overlaps with the maturation of the brain including the myelination process. Interestingly, there seems to be a link between myelin abnormalities and schizophrenia. The oligodendrocyte-derived myelin membranes in the CNS are highly enriched for lipids (cholesterol, phospholipids and glycosphingolipids), thereby pointing at lipid homeostasis as a relevant target for studying the genetics and pathophysiology of schizophrenia. The biosynthesis of fatty acids and cholesterol is regulated by the sterol regulatory element binding protein (SREBP) transcription factors SREBP1 and SREBP2, which are encoded by the SREBF1 and SREBF2 genes on chromosome 17p11.2 and 22q13.2, respectively. Here we review the evidence for the involvement of SREBF1 and SREBF2 as genetic risk factors in schizophrenia and discuss the role of myelination and SREBP-mediated lipid biosynthesis in the etiology, pathophysiology and drug treatment of schizophrenia.

Address: NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Electronic address: [email protected].; NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.; NORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

DOI: 10.1016/j.euroneuro.2016.07.011

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MeSH Terms: Antipsychotic Agents, Humans, Lipogenesis, Schizophrenia, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Transcription, Genetic