Serotonergic influence on depressive symptoms and trait anxiety is mediated by negative life events and frontal activation in children and adolescents

Depression and anxiety are common in childhood and adolescence. Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural function...

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Veröffentlicht in:	European child & adolescent psychiatry 2020-05, Vol.29 (5), p.691-706
Hauptverfasser:	Kneer, Katharina, Reinhard, Julia, Ziegler, Christiane, Slyschak, Anna, Schiele, Miriam, Vietz, Melanie, Peters, Katharina, Meisenzahl, Eva M., Pauli, Paul, Reif, Andreas, Deckert, Jürgen, Romanos, Marcel, Domschke, Katharina, Neufang, Susanne
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Sprache:	eng
Schlagworte:	Adolescents Anxiety Brain Brain mapping Child & adolescent psychiatry Child and Adolescent Psychiatry Childhood Children Emotional regulation Frontal gyrus Functional magnetic resonance imaging Genotype & phenotype Genotypes Innervation Medicine Medicine & Public Health Mental depression Negative events Negative life events Original Contribution Phenotypes Psychiatry Trait anxiety
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creator	Kneer, Katharina Reinhard, Julia Ziegler, Christiane Slyschak, Anna Schiele, Miriam Vietz, Melanie Peters, Katharina Meisenzahl, Eva M. Pauli, Paul Reif, Andreas Deckert, Jürgen Romanos, Marcel Domschke, Katharina Neufang, Susanne
description	Depression and anxiety are common in childhood and adolescence. Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural functioning in the fronto-limbic circuit. In this study, we examined the effect of the 5 - HTT LPR/rs25531 genotype on depressive symptoms and trait anxiety under the consideration of the amount of negative life events in healthy children and adolescents ( N = 389). In a subsample of 49 subjects, we performed fMRI to add fronto-limbic brain activation as a second interacting factor. Across all subjects, negative life events moderated the influence of the 5 - HTT LPR/rs25531 genotype on both depressive symptoms and trait anxiety. In the fMRI subsample, 5 - HTT LPR/rs25531 S + S/L G + S/L A + L G L A + L G L G genotype-associated left middle frontal gyrus (MFG) activation mediated the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms, however, only in combination with negative life events. Genetic influence on trait anxiety was predominantly mediated by negative life events; only L A L A genotype-specific activation in the right MFG worked as a mediator in combination with negative life events. The present findings hint towards distinct mechanisms mediating the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms and anxiety, with negative life events playing a crucial role in both phenotypes. With regard to depressive symptoms, however, this influence was only visible in combination with MFG activation, whereas, in anxiety, it was independent of brain activation.
doi_str_mv	10.1007/s00787-019-01389-3
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Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural functioning in the fronto-limbic circuit. In this study, we examined the effect of the 5 - HTT LPR/rs25531 genotype on depressive symptoms and trait anxiety under the consideration of the amount of negative life events in healthy children and adolescents ( N = 389). In a subsample of 49 subjects, we performed fMRI to add fronto-limbic brain activation as a second interacting factor. Across all subjects, negative life events moderated the influence of the 5 - HTT LPR/rs25531 genotype on both depressive symptoms and trait anxiety. 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With regard to depressive symptoms, however, this influence was only visible in combination with MFG activation, whereas, in anxiety, it was independent of brain activation.</description><identifier>ISSN: 1018-8827</identifier><identifier>EISSN: 1435-165X</identifier><identifier>DOI: 10.1007/s00787-019-01389-3</identifier><identifier>PMID: 31422473</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adolescents ; Anxiety ; Brain ; Brain mapping ; Child & adolescent psychiatry ; Child and Adolescent Psychiatry ; Childhood ; Children ; Emotional regulation ; Frontal gyrus ; Functional magnetic resonance imaging ; Genotype & phenotype ; Genotypes ; Innervation ; Medicine ; Medicine & Public Health ; Mental depression ; Negative events ; Negative life events ; Original Contribution ; Phenotypes ; Psychiatry ; Trait anxiety</subject><ispartof>European child & adolescent psychiatry, 2020-05, Vol.29 (5), p.691-706</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-d3f0bc022b376d19925e9d3e44dfa873f0eb911f7d58ce7694e19bbefb825c3c3</citedby><cites>FETCH-LOGICAL-c375t-d3f0bc022b376d19925e9d3e44dfa873f0eb911f7d58ce7694e19bbefb825c3c3</cites><orcidid>0000-0002-4927-2969</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00787-019-01389-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00787-019-01389-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,12828,27906,27907,30981,41470,42539,51301</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31422473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kneer, Katharina</creatorcontrib><creatorcontrib>Reinhard, Julia</creatorcontrib><creatorcontrib>Ziegler, Christiane</creatorcontrib><creatorcontrib>Slyschak, Anna</creatorcontrib><creatorcontrib>Schiele, Miriam</creatorcontrib><creatorcontrib>Vietz, Melanie</creatorcontrib><creatorcontrib>Peters, Katharina</creatorcontrib><creatorcontrib>Meisenzahl, Eva M.</creatorcontrib><creatorcontrib>Pauli, Paul</creatorcontrib><creatorcontrib>Reif, Andreas</creatorcontrib><creatorcontrib>Deckert, Jürgen</creatorcontrib><creatorcontrib>Romanos, Marcel</creatorcontrib><creatorcontrib>Domschke, Katharina</creatorcontrib><creatorcontrib>Neufang, Susanne</creatorcontrib><title>Serotonergic influence on depressive symptoms and trait anxiety is mediated by negative life events and frontal activation in children and adolescents</title><title>European child & adolescent psychiatry</title><addtitle>Eur Child Adolesc Psychiatry</addtitle><addtitle>Eur Child Adolesc Psychiatry</addtitle><description>Depression and anxiety are common in childhood and adolescence. Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural functioning in the fronto-limbic circuit. In this study, we examined the effect of the 5 - HTT LPR/rs25531 genotype on depressive symptoms and trait anxiety under the consideration of the amount of negative life events in healthy children and adolescents ( N = 389). In a subsample of 49 subjects, we performed fMRI to add fronto-limbic brain activation as a second interacting factor. Across all subjects, negative life events moderated the influence of the 5 - HTT LPR/rs25531 genotype on both depressive symptoms and trait anxiety. In the fMRI subsample, 5 - HTT LPR/rs25531 S + S/L G + S/L A + L G L A + L G L G genotype-associated left middle frontal gyrus (MFG) activation mediated the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms, however, only in combination with negative life events. Genetic influence on trait anxiety was predominantly mediated by negative life events; only L A L A genotype-specific activation in the right MFG worked as a mediator in combination with negative life events. The present findings hint towards distinct mechanisms mediating the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms and anxiety, with negative life events playing a crucial role in both phenotypes. With regard to depressive symptoms, however, this influence was only visible in combination with MFG activation, whereas, in anxiety, it was independent of brain activation.</description><subject>Adolescents</subject><subject>Anxiety</subject><subject>Brain</subject><subject>Brain mapping</subject><subject>Child & adolescent psychiatry</subject><subject>Child and Adolescent Psychiatry</subject><subject>Childhood</subject><subject>Children</subject><subject>Emotional regulation</subject><subject>Frontal gyrus</subject><subject>Functional magnetic resonance imaging</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Innervation</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Negative events</subject><subject>Negative life events</subject><subject>Original Contribution</subject><subject>Phenotypes</subject><subject>Psychiatry</subject><subject>Trait 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Psychiatry</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>29</volume><issue>5</issue><spage>691</spage><epage>706</epage><pages>691-706</pages><issn>1018-8827</issn><eissn>1435-165X</eissn><abstract>Depression and anxiety are common in childhood and adolescence. Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural functioning in the fronto-limbic circuit. In this study, we examined the effect of the 5 - HTT LPR/rs25531 genotype on depressive symptoms and trait anxiety under the consideration of the amount of negative life events in healthy children and adolescents ( N = 389). In a subsample of 49 subjects, we performed fMRI to add fronto-limbic brain activation as a second interacting factor. Across all subjects, negative life events moderated the influence of the 5 - HTT LPR/rs25531 genotype on both depressive symptoms and trait anxiety. In the fMRI subsample, 5 - HTT LPR/rs25531 S + S/L G + S/L A + L G L A + L G L G genotype-associated left middle frontal gyrus (MFG) activation mediated the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms, however, only in combination with negative life events. Genetic influence on trait anxiety was predominantly mediated by negative life events; only L A L A genotype-specific activation in the right MFG worked as a mediator in combination with negative life events. The present findings hint towards distinct mechanisms mediating the influence of 5 - HTT LPR/rs25531 genotype on depressive symptoms and anxiety, with negative life events playing a crucial role in both phenotypes. 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subjects	Adolescents Anxiety Brain Brain mapping Child & adolescent psychiatry Child and Adolescent Psychiatry Childhood Children Emotional regulation Frontal gyrus Functional magnetic resonance imaging Genotype & phenotype Genotypes Innervation Medicine Medicine & Public Health Mental depression Negative events Negative life events Original Contribution Phenotypes Psychiatry Trait anxiety
title	Serotonergic influence on depressive symptoms and trait anxiety is mediated by negative life events and frontal activation in children and adolescents
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