. 2015 Oct;54(10):832-40.

doi: 10.1016/j.jaac.2015.07.006. Epub 2015 Aug 4.

Subthreshold depression and regional brain volumes in young community adolescents

Hélène Vulser¹, Hervé Lemaitre¹, Eric Artiges², Ruben Miranda¹, Jani Penttilä³, Maren Struve⁴, Tahmine Fadai⁵, Viola Kappel⁶, Yvonne Grimmer⁴, Robert Goodman⁷, Argyris Stringaris⁷, Luise Poustka⁸, Patricia Conrod⁹, Vincent Frouin¹⁰, Tobias Banaschewski⁸, Gareth J Barker⁷, Arun L W Bokde¹¹, Uli Bromberg⁵, Christian Büchel⁵, Herta Flor⁴, Juergen Gallinat¹², Hugh Garavan¹³, Penny Gowland¹⁴, Andreas Heinz¹², Bernd Ittermann¹⁵, Claire Lawrence¹⁶, Eva Loth⁷, Karl Mann⁴, Frauke Nees⁸, Tomas Paus¹⁷, Zdenka Pausova¹⁸, Marcella Rietschel⁴, Trevor W Robbins¹⁹, Michael N Smolka²⁰, Gunter Schumann²¹, Jean-Luc Martinot¹, Marie-Laure Paillère-Martinot²²; IMAGEN Consortium (www.imagen-europe.com); IMAGEN Consortium www imagen-europe com

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ 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.
² 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.
³ Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland.
⁴ Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
⁵ Universitaetsklinikum Hamburg Eppendorf, Germany.
⁶ Psychosomatics and Psychotherapy, Charité-Universitätsmedizin, Berlin.
⁷ King's College London Institute of Psychiatry, London.
⁸ Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
⁹ King's College London Institute of Psychiatry, London; Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine Hospital, Montreal, Canada.
¹⁰ Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris.
¹¹ Institute of Neuroscience, Trinity College Dublin, Ireland.
¹² Campus CharitéMitte, Charité-Universitätsmedizin, Berlin.
¹³ Institute of Neuroscience, Trinity College Dublin, Ireland; University of Vermont, Burlington, VT.
¹⁴ School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
¹⁵ Physikalisch-TechnischeBundesanstalt (PTB), Braunschweig und Berlin, Berlin.
¹⁶ School of Psychology, University of Nottingham.
¹⁷ Rotman Research Institute, University of Toronto, Toronto.
¹⁸ The Hospital for Sick Children, University of Toronto.
¹⁹ Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom.
²⁰ Technische Universität Dresden, Dresden, Germany.
²¹ King's College London Institute of Psychiatry, London; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London.
²² 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.

PMID: 26407493
PMCID: PMC7614311
DOI: 10.1016/j.jaac.2015.07.006

Subthreshold depression and regional brain volumes in young community adolescents

Hélène Vulser et al. J Am Acad Child Adolesc Psychiatry. 2015 Oct.

. 2015 Oct;54(10):832-40.

doi: 10.1016/j.jaac.2015.07.006. Epub 2015 Aug 4.

Authors

Collaborators

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

Affiliations

¹ 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.
² 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.
³ Psychosocial Services Adolescent Outpatient Clinic Kauppakatu 14, Lahti, Finland.
⁴ Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.
⁵ Universitaetsklinikum Hamburg Eppendorf, Germany.
⁶ Psychosomatics and Psychotherapy, Charité-Universitätsmedizin, Berlin.
⁷ King's College London Institute of Psychiatry, London.
⁸ Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
⁹ King's College London Institute of Psychiatry, London; Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine Hospital, Montreal, Canada.
¹⁰ Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris.
¹¹ Institute of Neuroscience, Trinity College Dublin, Ireland.
¹² Campus CharitéMitte, Charité-Universitätsmedizin, Berlin.
¹³ Institute of Neuroscience, Trinity College Dublin, Ireland; University of Vermont, Burlington, VT.
¹⁴ School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
¹⁵ Physikalisch-TechnischeBundesanstalt (PTB), Braunschweig und Berlin, Berlin.
¹⁶ School of Psychology, University of Nottingham.
¹⁷ Rotman Research Institute, University of Toronto, Toronto.
¹⁸ The Hospital for Sick Children, University of Toronto.
¹⁹ Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom.
²⁰ Technische Universität Dresden, Dresden, Germany.
²¹ King's College London Institute of Psychiatry, London; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London.
²² 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.

PMID: 26407493
PMCID: PMC7614311
DOI: 10.1016/j.jaac.2015.07.006

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.

Keywords: MRI; gray matter; subthreshold depression; white matter.

PubMed Disclaimer

Conflict of interest statement

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, Penttil€ a, 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.

Figures

**Figure 1**
Regions with smaller gray matter volume (red) and white matter volume (green) in 119 adolescents with subthreshold depression versus 461 controls. Note: voxel level was set at p < .05 (familywise error–corrected for the whole brain). Results are superimposed on a T1-weighted magnetic resonance imaging scan of an adolescent brain from the Imagen database. (a) Sagittal slice; (b) transversal slice; (c) 3-dimensional representation (coronal and transversal slices). R = right.

**Figure 2**
Mediation of the gray matter medial prefrontal cortex on the relationship between subthreshold depression at age 14 years and depression at age 16 years in girls, using causal mediation analysis.

See this image and copyright information in PMC

Comment in

Subclinical psychiatric symptoms and the brain: what can developmental population neuroimaging bring to the table?
White T. White T. J Am Acad Child Adolesc Psychiatry. 2015 Oct;54(10):797-8. doi: 10.1016/j.jaac.2015.07.011. J Am Acad Child Adolesc Psychiatry. 2015. PMID: 26407488 No abstract available.

References

1. Pine DS, Cohen E, Cohen P, Brook J. Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder? Am J Psychiatry. 1999;156:133–135. - PubMed
1. Kessler RC, Angermeyer M, Anthony JC, et al. Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry. 2007;6:168–176. - PMC - PubMed
1. Bertha EA, Bal azs J. Subthreshold depression in adolescence: a systematic review. Eur Child Adolesc Psychiatry. 2013;22(10):589–603. - PubMed
1. Fergusson DM, Horwood LJ, Ridder EM, Beautrais AL. Subthreshold depression in adolescence and mental health outcomes in adulthood. Arch Gen Psychiatry. 2005;62(1):66–72. - PubMed
1. Klein DN, Shankman SA, Lewinsohn PM, Seeley JR. Subthreshold depressive disorder in adolescents: predictors of escalation to full-syndrome depressive disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:703–710. - PMC - PubMed

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Subthreshold depression and regional brain volumes in young community adolescents

Collaborators

Affiliations

Subthreshold depression and regional brain volumes in young community adolescents

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

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MeSH terms

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Medical