title: Peripheral DISC1 protein levels as a trait marker for schizophrenia and modulating effects of nicotine.
abstract: The Disrupted-in-Schizophrenia 1 (DISC1) protein plays a key role in behavioral control and vulnerability for mental illnesses, including schizophrenia. In this study we asked whether peripheral DISC1 protein levels in lymphocytes of patients diagnosed with schizophrenia can serve as a trait marker for the disease. Since a prominent comorbidity of schizophrenia patients is nicotine abuse or addiction, we also examined modulation of lymphocyte DISC1 protein levels in smokers, as well as the relationship between nicotine and DISC1 solubility status. We show decreased DISC1 levels in patients diagnosed with schizophrenia independent of smoking, indicating its potential use as a trait marker of this disease. In addition, lymphocytic DISC1 protein levels were decreased in smoking, mentally healthy individuals but not to the degree of overriding the trait level. Since DISC1 protein has been reported to exist in different solubility states in the brain, we also investigated DISC1 protein solubility in brains of rats treated with nicotine. Sub-chronic treatment with progressively increasing doses of nicotine from 0.25mg/kg to 1mg/kg for 15 days led to a decrease of insoluble DISC1 in the medial prefrontal cortex. Our results demonstrate that DISC1 protein levels in human lymphocytes are correlated with the diagnosis of schizophrenia independent of smoking and thus present a potential biomarker. Reduced DISC1 protein levels in lymphocytes of healthy individuals exposed to nicotine suggest that peripheral DISC1 could have potential for monitoring the effects of psychoactive substances.
authors.affiliation: Department Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Svenja V
authors.initials: SV
authors.lastname: Trossbach
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Fehsel
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Henning
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schäble
authors.affiliation: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Germany.
authors.forename: M Angelica de Souza
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Department Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany. Electronic address: ckorth@hhu.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003367:Cotinine / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012559:Schizophrenia / Q000097:blood* / Q000150:complications; D014029:Tobacco Use Disorder / Q000097:blood* / Q000150:complications
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine
keywords: Biomarker; DISC1; Drug monitoring; Lymphocyte; Nicotine; Schizophrenia