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

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Ämmälä , A-J , Urrila , A-S , Lahtinen , A , Santangeli , O , Hakkarainen , A , Kantojärvi , K , Castaneda , A E , Lundbom , N , Marttunen , M & Paunio , T 2019 , ' Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms ' , Sleep Medicine , vol. 61 , pp. 95-103 . https://doi.org/10.1016/j.sleep.2019.01.050

Title: Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms
Author: Ämmälä, Antti-Jussi; Urrila, Anna-Sofia; Lahtinen, Aleksandra; Santangeli, Olena; Hakkarainen, Antti; Kantojärvi, Katri; Castaneda, Anu E.; Lundbom, Nina; Marttunen, Mauri; Paunio, Tiina
Contributor: University of Helsinki, Department of Psychiatry
University of Helsinki, Staff Services
University of Helsinki, Medicum
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, Department of Psychiatry
University of Helsinki, National Institute for Health and Welfare (THL)
University of Helsinki, HUS Medical Imaging Center
University of Helsinki, HUS Psychiatry
University of Helsinki, University Management
Date: 2019-09
Language: eng
Number of pages: 9
Belongs to series: Sleep Medicine
ISSN: 1389-9457
URI: http://hdl.handle.net/10138/312866
Abstract: 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.
Subject: ANXIETY
Adolescence
BRAIN-DEVELOPMENT
DAYTIME
DEPRIVATION
Depression
Epigenetics
INSOMNIA
INVENTORY
MEMORY
Mood
OUTPATIENTS
PLASTICITY
Polysomnography
QUALITY
Sleepiness
3112 Neurosciences
3124 Neurology and psychiatry
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