Kuvaus

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 and Athens Insomnia Scale. 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.
Alkuperäiskielienglanti
LehtiSleep Medicine
ISSN1389-9457
DOI - pysyväislinkit
TilaJulkaistu - 7 maaliskuuta 2019
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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    @article{69cd731779094b2da1e091dcf1048192,
    title = "Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms",
    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 and Athens Insomnia Scale. 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.",
    keywords = "Adolescence, Depression, Epigenetics, Mood, Polysomnography, Sleepiness, Youth",
    author = "Antti-Jussi {\"A}mm{\"a}l{\"a} and Urrila, {Anna S.} and Aleksandra Lahtinen and Olena Santangeli and Antti Hakkarainen and Katri Kantoj{\"a}rvi and Castaneda, {Anu E.} and Nina Lundbom and Mauri Marttunen and Tiina Paunio",
    year = "2019",
    month = "3",
    day = "7",
    doi = "10.1016/j.sleep.2019.01.050",
    language = "English",
    journal = "Sleep Medicine",
    issn = "1389-9457",
    publisher = "Elsevier Scientific Publ. Co",

    }

    TY - JOUR

    T1 - Epigenetic dysregulation of genes related to synaptic long-term depression among adolescents with depressive disorder and sleep symptoms

    AU - Ämmälä, Antti-Jussi

    AU - Urrila, Anna S.

    AU - Lahtinen, Aleksandra

    AU - Santangeli, Olena

    AU - Hakkarainen, Antti

    AU - Kantojärvi, Katri

    AU - Castaneda, Anu E.

    AU - Lundbom, Nina

    AU - Marttunen, Mauri

    AU - Paunio, Tiina

    PY - 2019/3/7

    Y1 - 2019/3/7

    N2 - 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 and Athens Insomnia Scale. 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.

    AB - 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 and Athens Insomnia Scale. 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.

    KW - Adolescence

    KW - Depression

    KW - Epigenetics

    KW - Mood

    KW - Polysomnography

    KW - Sleepiness

    KW - Youth

    U2 - 10.1016/j.sleep.2019.01.050

    DO - 10.1016/j.sleep.2019.01.050

    M3 - Article

    JO - Sleep Medicine

    JF - Sleep Medicine

    SN - 1389-9457

    ER -