title: Subthreshold depression and regional brain volumes in young community adolescents.
abstract: OBJECTIVE
  Neuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years.
  
  
  METHODS
  High-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes.
  
  
  RESULTS
  Adolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial-prefrontal gray matter volume.
  
  
  CONCLUSIONS
  Subthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal-striatal-limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial-prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Vulser
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lemaitre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France; Orsay Hospital, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Artiges
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France.
authors.forename: Ruben
authors.initials: R
authors.lastname: Miranda
authors.affiliation: Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Penttilä
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Struve
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Germany.
authors.forename: Tahmine
authors.initials: T
authors.lastname: Fadai
authors.affiliation: Psychosomatics and Psychotherapy, Charité-Universitätsmedizin, Berlin.
authors.forename: Viola
authors.initials: V
authors.lastname: Kappel
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Grimmer
authors.affiliation: King's College London Institute of Psychiatry, London.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodman
authors.affiliation: King's College London Institute of Psychiatry, London.
authors.forename: Argyris
authors.initials: A
authors.lastname: Stringaris
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Poustka
authors.affiliation: King's College London Institute of Psychiatry, London; Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine Hospital, Montreal, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: King's College London Institute of Psychiatry, London.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Germany.
authors.forename: Uli
authors.initials: U
authors.lastname: Bromberg
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Campus CharitéMitte, Charité-Universitätsmedizin, Berlin.
authors.forename: Juergen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Ireland; University of Vermont, Burlington, VT.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Campus CharitéMitte, Charité-Universitätsmedizin, Berlin.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-TechnischeBundesanstalt (PTB), Braunschweig und Berlin, Berlin.
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: School of Psychology, University of Nottingham.
authors.forename: Claire
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: King's College London Institute of Psychiatry, London.
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto.
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.affiliation: The Hospital for Sick Children, University of Toronto.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: King's College London Institute of Psychiatry, London; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, Orsay, University Paris-Sud, Orsay, and University Paris Descartes, Sorbonne Paris Cité, France; Assistance Publique - Hôpitaux de Paris, Maison de Solenn, Cochin Hospital, Paris. Electronic address: ml.paillere@cch.aphp.fr.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Paillère-Martinot
mesh_terms: D000293:Adolescent; D001931:Brain Mapping / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D003863:Depression / Q000503:physiopathology*; D005060:Europe; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D011569:Psychiatric Status Rating Scales; D066127:White Matter / Q000473:pathology*
keywords: MRI; gray matter; subthreshold depression; white matter