title: Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder.
abstract: Alterations in brain glucose metabolism and in peripheral glucose metabolism have frequently been observed in major depressive disorder (MDD). The insulin independent glucose transporter 1 (GLUT1) plays a key role in brain metabolism while the insulin-dependent GLUT4 is the major glucose transporter for skeletal and cardiac muscle. We therefore examined methylation of GLUT1 and GLUT4 in fifty-two depressed inpatients and compared data to eighteen healthy comparison subjects. DNA methylation of the core promoter regions of GLUT1 and GLUT4 was assessed by bisulfite sequencing. Further factors determined were fasting glucose, cortisol, insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). We found significantly increased methylation of the GLUT1 in depressed inpatients compared to healthy comparison subjects (CG). Further findings comprise increased concentrations of fasting cortisol, glucose, insulin, and increased IL-6 and TNF-α. After six weeks of inpatient treatment, significantly lower GLUT1 methylation was observed in remitted patients compared to non-remitters. GLUT4 methylation was not different between depressed patients and CG, and did not differ between remitted and non-remitted patients. Although preliminary we conclude from our results that the acute phase of major depressive disorder is associated with increased GLUT1 methylation and mild insulin resistance. The successful treatment of depression is associated with normalization of GLUT1 methylation in remitters, indicating that this condition may be reversible. Failure of normalization of GLUT1 methylation in non-remitters may point to a possible role of impeded brain glucose metabolism in the maintenance of MDD.
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: kahl.kai@mh-hannover.de.
authors.forename: Kai G
authors.initials: KG
authors.lastname: Kahl
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Georgi
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Muschler
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.affiliation: Department of Cardiology and Angiology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleinert
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital of Lübeck, Ratzeburger Allee 160, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schweiger
authors.affiliation: Institute of Neuroradiology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kotsiari
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
mesh_terms: D000328:Adult; D001786:Blood Glucose; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000097:blood; D019175:DNA Methylation / Q000502:physiology*; D003865:Major Depressive Disorder / Q000097:blood / Q000150:complications* / Q000534:rehabilitation; D005215:Fasting / Q000097:blood / Q000502:physiology; D005260:Female; D044882:Glucose Metabolism Disorders / Q000209:etiology; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; C495677:SLC2A1 protein, human; D006854:Hydrocortisone
keywords: Epigenetics; Glucose metabolism; Glucose transporter 1; Glucose transporter 4; Major depressive disorder; Non-remission