This article is part of the Research Topic Brain connectivity analysis: Investigating brain disorders

Original Research ARTICLE

Front. Syst. Neurosci., 20 September 2010 | doi: 10.3389/fnsys.2010.00041

Whole brain resting-state analysis reveals decreased functional connectivity in major depression

  • 1 Leiden Institute for Brain and Cognition, Leiden, Netherlands
  • 2 Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
  • 3 Institute of Psychology, Leiden University, Leiden, Netherlands
  • 4 Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, UK
  • 5 Department of Clinical Neuroscience, Imperial College London, London, UK
  • 6 Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands
  • 7 Department of Radiology, Division of Image Processing, Leiden University Medical Center, Leiden, Netherlands
  • 8 Department of Psychiatry, VU Medical Center, Amsterdam, Netherlands
  • 9 BCN NeuroImaging Center, University of Groningen, Groningen, Netherlands

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

Keywords: major depression, resting-state functional magnetic resonance imaging, functional connectivity, independent component analysis, amygdala

Citation: Veer IM, Beckmann CF, van Tol M-J, Ferrarini L, Milles J, Veltman DJ, Aleman A, van Buchem MA, van der Wee NJ and Rombouts SARB (2010) Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Front. Syst. Neurosci. 4:41. doi: 10.3389/fnsys.2010.00041

Received: 29 April 2010; Paper pending published: 25 June 2010;
Accepted: 23 July 2010; Published online: 20 September 2010.

Edited by:

Silvina G. Horovitz, National Institutes of Health, USA

Reviewed by:

Cameron Craddock, Baylor College of Medicine, USA
Martin Walter, Otto-von-Guericke-Universität Magdeburg, Germany

Copyright: © 2010 Veer, Beckmann, van Tol, Ferrarini, Milles, Veltman, Aleman, van Buchem, van der Wee and Rombouts. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: Ilya M. Veer, Department of Radiology, Leiden University Medical Center, Postzone C2-S, P.O. Box 9600, 2300 RC Leiden, Netherlands. e-mail:

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