Brain structural thickness and resting state autonomic function in adolescents with major depression

Julian Koenig, Melinda Westlund Schreiner, Bonnie Klimes-Dougan, Benjamin Ubani, Bryon Mueller, Michael Kaess, Kathryn R. Cullen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Major depressive disorder (MDD) has been associated with abnormalities in cortical thickness and autonomic function. Adolescence is a time notable for brain development and MDD onset. In healthy adolescents, greater resting state vagal activity (RVA) is associated with lower cortical thickness. The relationship between brain structural thickness and RVA in adolescents with MDD has not previously been studied. This secondary analysis drew on a sample of 37 non-depressed controls and 53 adolescents with MDD. Resting state heart rate and two indices of RVA (HF-HRV and RMSSD) were recorded during a neuroimaging session. Cortical thickness within fronto-limbic regions of interest was measured using Freesurfer analysis of T1-weighted high-resolution structural images. Self-reports of depression severity showed a significant interaction with cortical thickness of the right insula in predicting RMSSD [t=2.22, P=0.030, β=5.44; model fit of the interaction term as indicated by the 'Bayes Factor' (BF): 7.58] and HF-HRV (t=2.09, P=0.041, β=4.72; BF: 7.94). Clinician ratings of depression severity showed further interactions. Findings underscore the important relationships between RVA and cortical development, suggesting two possible explanations: (i) in adolescent MDD, greater fronto-limbic thickness is compensatory for deficits in autonomic regulation or (ii) increased autonomic arousal results in delayed fronto-limbic maturation. Longitudinal research is necessary to further clarify the nature of the relationship between autonomic functioning and cortical development.

Original languageEnglish (US)
Pages (from-to)741-753
Number of pages13
JournalSocial Cognitive and Affective Neuroscience
Issue number7
StatePublished - 2018

Bibliographical note

Funding Information:
The study was funded by grants to Dr Cullen including the National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School and the Minnesota Medical Foundation, as well as a grant to Dr Klimes-Dougan from the Deborah E. Powell Center for Women’s Health at the University of Minnesota. Dr Koenig is supported by a Physician-Scientist-Fellowship provided by the Medical School, University of Heidelberg, Germany, and acknowledges the financial support through a PostDoctoral Scholarship provided by the Daimler and Benz Foundation (Ladenburg, Germany) and the Thrasher Research Fund Early Career Award provided by the Thrasher Research Fund (Salt Lake City, UT, USA). These resources supported the roles of design and conduct of the study; collection, management and analysis of the data; and interpretation of results and preparation of the publication. We acknowledge financial support by the Deutsche Forschungsgemeinschaft within the funding programme Open Access Publishing, by the Baden-Württemberg Ministry of Science, Research and the Arts and by the Ruprecht-Karls-Universität Heidelberg.


  • Adolescents
  • Autonomic function
  • Cortical thickness
  • Major depressive disorder
  • Vagal activity

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