Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms

Autor: Olena Santangeli, Anu E. Castaneda, Antti Hakkarainen, Nina Lundbom, Mauri Marttunen, Katri Kantojärvi, Anna-Sofia Urrila, Aleksandra Lahtinen, Tiina Paunio, Antti-Jussi Ämmälä
Přispěvatelé: Department of Psychiatry, Doctoral Programme in Integrative Life Science, Department of Public Health, Medicum, HUS Children and Adolescents, Department of Physiology, University of Helsinki, Department of Forensic Medicine, Department of Medical and Clinical Genetics, Doctoral Programme in Social Sciences, Clinicum, HUS Medical Imaging Center, Doctoral Programme in Clinical Research, HUS Psychiatry, Doctoral Programme Brain & Mind, Doctoral Programme in Population Health
Rok vydání: 2019
Předmět:
Zdroj: Sleep Medicine. 61:95-103
ISSN: 1389-9457
DOI: 10.1016/j.sleep.2019.01.050
Popis: Funding Information: Financial support for the study includes a special federal grant ( TYH 2013342 ) to T.P. and funding from the Academy of Finland (grant number 276612 to A.S.U. and number 290039 to T.P.), Emil Aaltonen Foundation , Finnish Medical Foundation , Finnish Brain Foundation , Orion-Farmos Research Foundation , Päivikki and Sakari Sohlberg Foundation , and the Foundation for Psychocultural Research . We also wish to thank Auli Toivola for her valuable contribution regarding laboratory work. Publisher Copyright: © 2019 Elsevier B.V. Objectives: This study aimed to test the hypothesis that sleep and depression have independent effects on brain development and plasticity in adolescents, and that these changes are reflected in changes in the epigenome. Methods: Participants were 17 medication-free adolescent boys (age 16.05 +/- 0.80 years, mean +/- standard deviation (SD); eight cases with depression and sleep symptoms, nine healthy controls). Sleep was assessed by polysomnography recordings and the Pediatric Daytime Sleepiness Scale (PDSS) and Athens Insomnia Scale (AIS). Participants underwent a clinical evaluation. DNA methylation of blood leukocytes was measured by Illumina 450K array, and Ingenuity Pathway analysis was applied to identify the most significant pathways with differentially methylated positions (DMPs). Secondary analysis of the identified loci included linear correlations between methylation and the subjectively rated scales of sleep, depression and sleep microarchitecture. Results: Due to small sample size, we found no genome-wide significant differences in methylation between cases and controls. However, pathway analysis identified the synaptic long-term depression (LTD) canonical pathway (p = 0.00045) when the best 500 DMPs from the original case-control design were included. A flattened dissipation of slow wave sleep, tiredness and depression severity values correlated with five of 10 sites from the LTD pathway (IGF1R, PLAG16, PLA2R1, PPP2C5 and ERK12) in the secondary analysis when the case-control status was controlled for. Conclusion: Among adolescents, depressive disorder with sleep symptoms is associated with a distinctive epigenetic pattern of DNA methylation in blood leukocytes. The enrichment of DMPs on genes related to synaptic LTD emphasizes the role of sleep in synaptic plasticity and the widespread physiological consequences of disturbed sleep. (C) 2019 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
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