Early Variations in White Matter Microstructure and Depression Outcome in Adolescents With Subthreshold Depression.

Hélène Vulser, Marie-Laure Paillère Martinot, Eric Artiges, Ruben Miranda, Jani Penttilä, 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 Desrivières, Herta Flor, Vincent Frouin, Juergen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Frauke Nees, Dimitri Papadopoulos-Orfanos, Tomas Paus, Luise Poustka, Sarah Rodehacke, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Jean-Luc Martinot, Hervé Lemaitre,
AJP. 2018-12-01; 175(12): 1255-1264
DOI: 10.1176/appi.ajp.2018.17070825

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OBJECTIVE: White matter microstructure alterations have recently been associated
with depressive episodes during adolescence, but it is unknown whether they
predate depression. The authors 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 control
subjects (N=336) drawn from a community-based cohort were compared using
diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at
age 14 to assess white matter microstructure. They were followed up at age 16 to
assess depression. Probabilistic tractography was used to reconstruct white
matter streamlines spreading from the regions identified in the TBSS analysis and
along bundles implicated in emotion regulation, the uncinate fasciculus and the
cingulum. The authors 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 subthreshold depression at baseline and depression at follow-up 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 may denote a higher risk of transition to
depression in adolescents.


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