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Early variations in white matter microstructure and depression outcome in adolescents with subthreshold-depression

Vulser, Hélène; Martinot, Marie-Laure Paillère; Artiges, Eric; Miranda, Ruben; Pentilla, Jani; Grimmer, Yvonne; van Noort, Betteke M.; Stringaris, Argyris; Struve, Maren; Fadai, Tahmine; Kappel, Viola; Goodman, Robert; Tzavara, Eleni; Massaad, Charbel; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L.W.; Bromberg, Uli; Brühl, Rüdiger; Büchel, Christian; Cattrell, Anna; Conrod, Patricia; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Proustka, Louise; Rodehacke, Sarah; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Martinot, Jean-Luc; Lemaitre, Hervé


Hélène Vulser

Marie-Laure Paillère Martinot

Eric Artiges

Ruben Miranda

Jani Pentilla

Yvonne Grimmer

Betteke M. van Noort

Argyris Stringaris

Maren Struve

Tahmine Fadai

Viola Kappel

Robert Goodman

Eleni Tzavara

Charbel Massaad

Tobias Banaschewski

Gareth J. Barker

Arun L.W. Bokde

Uli Bromberg

Rüdiger Brühl

Christian Büchel

Anna Cattrell

Patricia Conrod

Sylvane Desrivieres

Herta Flor

Vincent Frouin

Jürgen Gallinat

Hugh Garavan

Andreas Heinz

Frauke Nees

Dimitri Papadopoulos-Orfanos

Tomáš Paus

Louise Proustka

Sarah Rodehacke

Michael N. Smolka

Henrik Walter

Robert Whelan

Gunter Schumann

Jean-Luc Martinot

Hervé Lemaitre


Objective: White matter microstructure alterations have recently been associated with adolescence depressive episodes, but it is unknown whether they predate depression. We investigated whether subthreshold-depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome.
Method: Adolescents with subthreshold-depression (n=96) and healthy controls (n=336), drawn from a community-based cohort, were compared using diffusion tensor imaging and whole-brain tractbased spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followedup at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines from the TBSS analysis resulting regions, and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. We searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold-depression and depression at follow-up, and then explored the specificity of the findings.
Results: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold-depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between baseline subthreshold-depression and follow-up depression was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression.
Conclusions: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex might denote higher risk of transition to depression in adolescents.


Vulser, H., Martinot, M. P., Artiges, E., Miranda, R., Pentilla, J., Grimmer, Y., …Lemaitre, H. (2018). Early variations in white matter microstructure and depression outcome in adolescents with subthreshold-depression. American Journal of Psychiatry, 175(12), 1255-1264.

Journal Article Type Article
Acceptance Date May 21, 2018
Online Publication Date Aug 16, 2018
Publication Date Dec 1, 2018
Deposit Date May 22, 2018
Publicly Available Date Aug 17, 2019
Journal American Journal of Psychiatry
Print ISSN 0002-953X
Electronic ISSN 1535-7228
Publisher American Psychiatric Publishing
Peer Reviewed Peer Reviewed
Volume 175
Issue 12
Pages 1255-1264
Public URL
Publisher URL
Additional Information The official published article is available online at


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