Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder.

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.

Morningness-eveningness and educational outcomes: the lark has an advantage over the owl at high school.

BACKGROUND: Chronotype refers to individuals' preference for morning or evening activities. Its two dimensions (morningness and eveningness) are related to a number of academic outcomes. AIMS: The main goal of the study was to investigate the incremental validity of chronotype as a predictor of academic achievement after controlling for a number of traditional predictors. In so doing, a further aim was ongoing validation of a chronotype questionnaire, the Lark-Owl Chronotype Indicator. SAMPLE: The sample comprised 272 students attending 9th and 10th grades at five German high schools. Data was also obtained from 132 parents of these students. METHOD: Students were assessed in class via self-report questionnaires and a standardized cognitive test. Parents filled out a questionnaire at home. The incremental validity of chronotype was investigated using hierarchical linear regression. Validity of the chronotype questionnaire was assessed by correlating student ratings of their chronotype with behavioural data on sleep, food intake, and drug consumption and with parent ratings of chronotype. RESULTS: Eveningness was a significant (negative) predictor of overall grade point average (GPA), math-science GPA, and language GPA, after cognitive ability, conscientiousness, need for cognition, achievement motivation, and gender were held constant. Validity evidence for the chronotype measure was established by significant correlations with parent-ratings and behavioural data. CONCLUSIONS: Results point to the possible discrimination of adolescents with a proclivity towards eveningness at school. Possible explanations for the relationship between chronotype and academic achievement are presented. Implications for educational practice are also discussed.