Subthreshold Depression and Regional Brain Volumes in Young Community Adolescents - 23/09/15

Doi : 10.1016/j.jaac.2015.07.006

Hélène Vulser, MD ^a, Hervé Lemaitre, PhD ^a, Eric Artiges, MD, PhD ^a,^c, Ruben Miranda, MPsych ^a, Jani Penttilä, MD, PhD ^g, Maren Struve, PhD ^h, Tahmine Fadai, MD ⁱ, Viola Kappel, PhD ^j, Yvonne Grimmer, MD ^h, Robert Goodman, PhD, FRCPsych ^e, Argyris Stringaris, MD, PhD, MRCPsych ^e, Luise Poustka, MD ^k, Patricia Conrod, PhD ^e,^f, Vincent Frouin, PhD ^d, Tobias Banaschewski, MD, PhD ^k, Gareth J. Barker, PhD ^e, Arun L.W. Bokde, PhD ^l, Uli Bromberg, MD ⁱ, Christian Büchel, MD ⁱ, Herta Flor, PhD ^h, Juergen Gallinat, MD ^o, Hugh Garavan, PhD ^l,^p, Penny Gowland, PhD ⁿ, Andreas Heinz, MD ^o, Bernd Ittermann, PhD ^q, Claire Lawrence, PhD ^r, Eva Loth, PhD ^e, Karl Mann, MD ^h, Frauke Nees, PhD ^k, Tomas Paus, MD, PhD ^s, Zdenka Pausova, MD ^t, Marcella Rietschel, MD ^h, Trevor W. Robbins, PhD ^u, Michael N. Smolka, MD ^v, Gunter Schumann, MD ^e,^m, Jean-Luc Martinot, MD, PhD ^a, Marie-Laure Paillère-Martinot, MD, PhD ^a,^b,^⁎
for the
IMAGEN Consortium (www.imagen-europe.com)
J. Dalley, N. Subramaniam, D. Theobald, C. Bach, M. Fauth-Bühler, S. Millenet, R. Spanagel, L. Albrecht, N. Ivanov, M. Rapp, J. Reuter, N. Strache, A. Ströhle, C. Lalanne, J.B. Poline, Y. Schwartz, B. Thyreau, M. Lathrop, J. Ireland, J. Rogers, N. Bordas, Z. Bricaud, I. Filippi, A. Galinowski, F. Gollier-Briant, J. Massicotte, C. Andrew, A. Cattrell, S. Desrivieres, D. Hall, S. Havatzias, T. Jia, C. Mallik, C. Nymberg, L. Reed, B. Ruggeri, L. Smith, K. Stueber, L. Topper, H. Werts, R. Brühl, A. Ihlenfeld, B. Walaszek, T. Hübner, K. Müller, S. Ripke, S. Rodehacke, E. Mennigen, D. Schmidt, N. Vetter, V. Ziesch, D. Carter, C. Connolly, S. Nugent, J. Jones, R. Whelan, J. Yacubian, S. Schneider, K. Head, N. Heym, C. Newman, A. Tahmasebi, D. Stephens

^a 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
^b Assistance Publique – Hôpitaux de Paris, Maison de Solenn, Cochin Hospital, Paris
^c Orsay Hospital, France
^d Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris
^e King's College London Institute of Psychiatry, London
^f Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine Hospital, Montreal, Canada
^g Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland
^h Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany
ⁱ Universitaetsklinikum Hamburg Eppendorf, Germany
^j Psychosomatics and Psychotherapy, Charité-Universitätsmedizin, Berlin
^k Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany
^l Institute of Neuroscience, Trinity College Dublin, Ireland
^m MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London
ⁿ School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
^o Campus CharitéMitte, Charité-Universitätsmedizin, Berlin
^p University of Vermont, Burlington, VT
^q Physikalisch-TechnischeBundesanstalt (PTB), Braunschweig und Berlin, Berlin
^r School of Psychology, University of Nottingham
^s Rotman Research Institute, University of Toronto, Toronto
^t The Hospital for Sick Children, University of Toronto
^u Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom
^v Technische Universität Dresden, Dresden, Germany

^∗Correspondence to Dr. Marie-Laure Paillère-Martinot, Maison de Solenn, Hôpital Cochin, 97 Boulevard de Port-Royal, 75014 Paris, FranceMaison de Solenn, Hôpital Cochin97 Boulevard de Port-Royal75014 ParisFrance

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.

Method

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.

Conclusion

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.

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Key Words : subthreshold depression, MRI, gray matter, white matter

Plan

Participant Characteristics

Global Brain Tissue Volumes

Voxel-Based Morphometry

Causal Mediation Analyses

Discussion

	This article is discussed in an editorial by Dr. Tonya White on page 797.
	Clinical guidance is available at the end of this article.
	This work received support from the European Union-funded FP6 Integrated Project IMAGEN (LSHMCT-2007-037286), the FP7 project IMAGEMEND and the Innovative Medicine Initiative Project EUAIMS (115300-2), a Medical Research Council Programme Grant (93558), the Swedish funding agency FORMAS, the Wellcome Trust (University of Cambridge), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Department of Health UK, the Bundesministerium für Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the French funding agency ANR (ANR-12-SAMA-0004), an Eranet–Neuron grant (project AF12-NEUR0008-01 - WM2NA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris-Descartes-University (collaborative-project-2010), Paris-Sud-University (IDEX-2012), the Fondation de France, and the Mission Interministérielle de Lutte-contre-la-Drogue-et-la-Toxicomanie (MILDT).
	Other Imagen Consortium collaborators are as follows: J. Dalley, N. Subramaniam, D. Theobald from Cambridge University; C. Bach, M. Fauth-Bühler, S. Millenet, R. Spanagel from Central Institute of Mental Health, Mannheim; L. Albrecht, N. Ivanov, M. Rapp, J. Reuter, N. Strache, A. Ströhle from Charité Hospital, Berlin; C. Lalanne, J.B. Poline, Y. Schwartz, B. Thyreau from Commissariat à l'Energie Atomique, Paris; M. Lathrop from Centre National de Génotypage, Evry; J. Ireland, J. Rogers from Delosis; N. Bordas, Z. Bricaud, I. Filippi, A. Galinowski, F. Gollier-Briant, J. Massicotte from INSERM; C. Andrew, A. Cattrell, S. Desrivieres, D. Hall, S. Havatzias, T. Jia, C. Mallik, C. Nymberg, L. Reed, B. Ruggeri, L. Smith, K. Stueber, L. Topper, H. Werts from the Institute of Psychiatry, London; R. Brühl, A. Ihlenfeld, B. Walaszek from Physikalisch-TechnischeBundesanstalt (PTB), Berlin; T. Hübner, K. Müller, S. Ripke, S. Rodehacke, E. Mennigen, D. Schmidt, N. Vetter, V. Ziesch from University of Dresden; D. Carter, C. Connolly, S. Nugent from Trinity College Dublin; J. Jones, R. Whelan from University College Dublin; J. Yacubian, S. Schneider from University of Hamburg; K. Head, N. Heym, C. Newman from University of Nottingham; A. Tahmasebi from University of Toronto; D. Stephens from University of Sussex.
	Disclosure: Dr. Goodman is the owner of Youthinmind, Ltd., which provides no-cost and low-cost software and websites related to the Development and Well-Being Assessment and the Strengths-and-Difficulties Questionnaire. Dr. Stringaris has received grant or research support from the Wellcome Trust, the National Institute for Health Research (NIHR), and the Department of Health UK. He has received royalties from Cambridge University Press for his book The Maudsley Reader in Phenomenological Psychiatry. Dr. Barker has received honoraria for teaching from General Electric, acted as consultant of IXICO, and was granted US patent 2015-0123662A1. Dr. Robbins has received compensation as a consultant for Cambridge Cognition. Dr. Paillère-Martinot has received compensation from Janssen-Cilag for CME activities. Drs. Vulser, Lemaitre, Artiges, Penttilä, Struve, Fadai, Kappel, Grimmer, Poustka, Conrod, Frouin, Banaschewski, Bokde, Bromberg, Büchel, Flor, Gallinat, Garavan, Gowland, Heinz, Ittermann, Lawrence, Loth, Mann, Nees, Paus, Pausova, Rietschel, Smolka, Schumann, Martinot, and Mr. Miranda report no biomedical financial interests or potential conflict of interest.

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Vol 54 - N° 10

P. 832-840 - octobre 2015 Retour au numéro

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Subthreshold Depression and Regional Brain Volumes in Young Community Adolescents - 23/09/15

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