title: Activated immune-inflammatory pathways are associated with long-standing depressive symptoms: Evidence from gene-set enrichment analyses in the Young Finns Study.
abstract: We used genome wide expression (GWE) data of circulating blood cells and pathway analysis to investigate the inflammatory and other molecular pathways that may be associated with long-standing depressive symptoms. Participants were 607 women and 316 men (mean age 42 years) from the Young Finns Study who participated in three consecutive study phases in 2001, 2007 and 2012. Using Gene-set enrichment analyses (GSEA) we focused our analyses to pathways (available in MSigDB database) that are likely to affect immunological and inflammatory processes. GSEA were performed for blood cell GWE data in 2012. Depressive symptoms were assessed using a modified 21-item Beck Depression Inventory in each of the three study phases. Participants who scored in the top quartile of depressive symptoms in each of the three measurement points (n = 191) differed from other participants (n = 732) in several gene-set pathways related to inflammatory processes or immune-inflammatory signaling including interleukin (IL-1) pathway, and pathways related to various immuno-inflammatory processes, such as toll-like, the NEF protein, the nuclear factor kB, the kinase AKT and the mature B cell antigen receptor pathway (false discovery rates, FDRs<0.12). The results provide novel genome wide molecular evidence that support the association between chronic depressive symptoms and altered immune-inflammatory regulation.
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland. Electronic address: marko.elovainio@thl.fi.
authors.forename: Marko
authors.initials: M
authors.lastname: Elovainio
authors.affiliation: Deparment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Taipale
authors.affiliation: Deparment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Deparment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Mononen
authors.affiliation: Deparment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Jokela
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland; Helsinki Collegium for Advanced Studies, P.O. Box 24, FI-00014, University of Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Pulkki-Råback
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hanover, Germany; Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland.
authors.forename: Christian
authors.initials: C
authors.lastname: Hakulinen
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Hintsa
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland; Department of Epidemiology and Public Health University College London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Keltikangas-Järvinen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, University of Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.affiliation: Deparment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000328:Adult; D003866:Depressive Disorder / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
keywords: Gene expression depression; Gene set pathways; Gene-set enrichment analyses