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Am J Psychiatry. 2018 Dec 1;175(12):1255-1264. doi: 10.1176/appi.ajp.2018.17070825. Epub 2018 Aug 16.

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

Author information

1
From INSERM, Research Unit UMR 1000, Research Unit "Neuroimaging and Psychiatry," Paris; University Paris-Saclay, Gif-sur-Yvette, France; University Paris Descartes, Paris; Assistance Publique-Hôpitaux de Paris, Department of Psychiatry, Western Paris University Hospital group, Paris; Assistance Publique-Hôpitaux de Paris, Child and Adolescent Psychiatry Department, Pitié-Salpêtrière Hospital, Paris the Center for Neuroimaging Research, Brain and Spine Institute, Paris; the Department of Psychiatry, Orsay Hospital, Orsay, France; the Department of Social and Health Care, Psychosocial Services Adolescent Outpatient Clinic, Lahti, Finland; the Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy and the Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin; the Department of Child and Adolescent Psychiatry, the Centre for Neuroimaging Sciences, the Medical Research Council-Social, Genetic, and Developmental Psychiatry Centre, and the Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; the University Medical Center Hamburg-Eppendorf, Hamburg; Neuroscience Paris Seine-IBPS (CNRS UMR8246/Inserm U1130/UMPC UMCR18); Centre National de la Recherche Scientifique, Research Unit UMR 8194, Paris; the Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin; Physikalisch-Technische Bundesanstalt, Berlin; the Department of Psychiatry, University of Montreal, CHU Sainte-Justine Hospital, Montreal; Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris; the Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg; the Departments of Psychiatry and Psychology, University of Vermont, Burlington; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, U.K.; the Rotman Research Institute, University of Toronto, Toronto; the Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Austria; the Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany; the Department of Psychology, University College, Dublin.

Abstract

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.

KEYWORDS:

Adolescents; Brain Imaging Techniques; Mood Disorders-Unipolar; Neuroanatomy; Outcome Studies

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