DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study

Translational Psychiatry, vol. 12, pp. 317

Abstract

The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.

Authors 9

1. Melina Felicitas Wiedmann corresponding

   Technische Universität Dresden

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany. melina.wiedmann@uniklinikum-dresden.de

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany

2. Sören Kuitunen‐Paul

   Chemnitz University of Technology · Technische Universität Dresden

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany

   Technische Universität Chemnitz, Chair for Clinical Psychology and Psychotherapy, Chemnitz, Germany

3. Lukas Andreas Basedow

   Technische Universität Dresden

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany

4. Max Wolff

   Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany

   Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany

5. Nataliya Di Donato

   Technische Universität Dresden

   Affiliation as printed

   Technische Universität Dresden, University Hospital, Institute for Clinical Genetics, Dresden, Germany

6. Julia Franzen Aachen

   RWTH Aachen University

   Affiliation as printed

   Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany

7. Wolfgang Wagner Aachen

   RWTH Aachen University

   Affiliation as printed

   Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany

8. Veit Roessner

   Technische Universität Dresden

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany

9. Yulia Golub

   Technische Universität Dresden

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany