Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

Hdl Handle:
http://hdl.handle.net/10147/271521
Title:
Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.
Authors:
Frodl, T; Carballedo, A; Hughes, M M; Saleh, K; Fagan, A; Skokauskas, N; McLoughlin, D M; Meaney, J; O'Keane, V; Connor, T J
Affiliation:
Department of Psychiatry and Institute of Neuroscience, Adelaide and Meath Hospital incorporating the National Children's Hospital and St James' s Hospital, University Dublin, Trinity College, Dublin, Ireland. thomas.frodl@tcd.ie
Citation:
Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. 2012, 2:e88 Transl Psychiatry
Journal:
Translational psychiatry
Issue Date:
2012
URI:
http://hdl.handle.net/10147/271521
DOI:
10.1038/tp.2012.14
PubMed ID:
22832853
Abstract:
Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.
Item Type:
Article
Language:
en
MeSH:
Adult; Amygdala; C-Reactive Protein; Child; Child Abuse; Depressive Disorder, Major; Dominance, Cerebral; Female; Gene Expression; Hippocampus; Humans; Immediate-Early Proteins; Interleukin-6; Male; Middle Aged; Organ Size; Protein-Serine-Threonine Kinases; RNA, Messenger; Receptors, Glucocorticoid; Reference Values; Statistics as Topic; Transcription Factors
ISSN:
2158-3188

Full metadata record

DC FieldValue Language
dc.contributor.authorFrodl, Ten_GB
dc.contributor.authorCarballedo, Aen_GB
dc.contributor.authorHughes, M Men_GB
dc.contributor.authorSaleh, Ken_GB
dc.contributor.authorFagan, Aen_GB
dc.contributor.authorSkokauskas, Nen_GB
dc.contributor.authorMcLoughlin, D Men_GB
dc.contributor.authorMeaney, Jen_GB
dc.contributor.authorO'Keane, Ven_GB
dc.contributor.authorConnor, T Jen_GB
dc.date.accessioned2013-03-08T13:58:04Z-
dc.date.available2013-03-08T13:58:04Z-
dc.date.issued2012-
dc.identifier.citationReduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. 2012, 2:e88 Transl Psychiatryen_GB
dc.identifier.issn2158-3188-
dc.identifier.pmid22832853-
dc.identifier.doi10.1038/tp.2012.14-
dc.identifier.urihttp://hdl.handle.net/10147/271521-
dc.description.abstractNeuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Translational psychiatryen_GB
dc.subject.meshAdult-
dc.subject.meshAmygdala-
dc.subject.meshC-Reactive Protein-
dc.subject.meshChild-
dc.subject.meshChild Abuse-
dc.subject.meshDepressive Disorder, Major-
dc.subject.meshDominance, Cerebral-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshHippocampus-
dc.subject.meshHumans-
dc.subject.meshImmediate-Early Proteins-
dc.subject.meshInterleukin-6-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOrgan Size-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshRNA, Messenger-
dc.subject.meshReceptors, Glucocorticoid-
dc.subject.meshReference Values-
dc.subject.meshStatistics as Topic-
dc.subject.meshTranscription Factors-
dc.titleReduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Psychiatry and Institute of Neuroscience, Adelaide and Meath Hospital incorporating the National Children's Hospital and St James' s Hospital, University Dublin, Trinity College, Dublin, Ireland. thomas.frodl@tcd.ieen_GB
dc.identifier.journalTranslational psychiatryen_GB
dc.description.provinceLeinsteren

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