Journal of Neural Transmission

, Volume 124, Issue 5, pp 589–605 | Cite as

Diagnostic classification of unipolar depression based on resting-state functional connectivity MRI: effects of generalization to a diverse sample

  • Benedikt Sundermann
  • Stephan Feder
  • Heike Wersching
  • Anja Teuber
  • Wolfram Schwindt
  • Harald Kugel
  • Walter Heindel
  • Volker Arolt
  • Klaus Berger
  • Bettina Pfleiderer
Psychiatry and Preclinical Psychiatric Studies - Original Article


In small, selected samples, an approach combining resting-state functional connectivity MRI and multivariate pattern analysis has been able to successfully classify patients diagnosed with unipolar depression. Purposes of this investigation were to assess the generalizability of this approach to a large clinically more realistic sample and secondarily to assess the replicability of previously reported methodological feasibility in a more homogeneous subgroup with pronounced depressive symptoms. Two independent subsets were drawn from the depression and control cohorts of the BiDirect study, each with 180 patients with and 180 controls without depression. Functional connectivity either among regions covering the gray matter or selected regions with known alterations in depression was assessed by resting-state fMRI. Support vector machines with and without automated feature selection were used to train classifiers differentiating between individual patients and controls in the entire first subset as well as in the subgroup. Model parameters were explored systematically. The second independent subset was used for validation of successful models. Classification accuracies in the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In the subgroup with higher depression severity, three out of 90 models performed significantly above chance (60.8–61.7% at independent validation). In conclusion, common classification methods previously successful in small homogenous depression samples do not immediately translate to a more realistic population. Future research to develop diagnostic classification approaches in depression should focus on more specific clinical questions and consider heterogeneity, including symptom severity as an important factor.


fMRI Functional connectivity Classification MVPA Depression 



The authors thank all study participants and the entire team of the BiDirect study, including collaborators in associated institutions. Thanks also go to Jens Bode for support with the execution of data analyses.

Compliance with ethical standards

Conflicts of interest

The following authors declared additional financial relationships not directly related to this work: BP has received grants from EU European Social Fund and the German Ministry of Education and Research. VA is board member for Lundbeck, Otsuka, Servier and Tromsdorff and has received honoraria from Lundbeck, Otsuka and Servier.


BiDirect is funded by a research Grant (FZK: 01ER0816) from the German Federal Ministry of Education and Research (BMBF). This analysis was additionally supported by BMBF Grant 01ER1205.

Ethical approval

The study was approved by the ethics committee of the University of Münster and the Westphalian Chamber of Physicians in Münster. All procedures were done in accordance with the Helsinki Declaration.

Informed consent

Written informed consent for participation in the study was obtained from all participants.

Supplementary material

702_2016_1673_MOESM1_ESM.pdf (87 kb)
Online Resource 1 (ESM_1.pdf): supplementary methods (PDF 87 kb)
702_2016_1673_MOESM2_ESM.pdf (259 kb)
Online Resource 2 (ESM_2.pdf): supplementary Tables 1–6 with detailed classification results and subgroup characteristics (PDF 258 kb)
702_2016_1673_MOESM3_ESM.pdf (25 kb)
Online Resource 3 (ESM_3.pdf): p value histograms of univariate group comparisons (PDF 24 kb)


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Benedikt Sundermann
    • 1
  • Stephan Feder
    • 1
  • Heike Wersching
    • 2
  • Anja Teuber
    • 2
  • Wolfram Schwindt
    • 1
  • Harald Kugel
    • 1
  • Walter Heindel
    • 1
  • Volker Arolt
    • 3
  • Klaus Berger
    • 2
  • Bettina Pfleiderer
    • 1
  1. 1.Department of Clinical RadiologyUniversity Hospital MünsterMünsterGermany
  2. 2.Institute of Epidemiology and Social MedicineUniversity of MünsterMünsterGermany
  3. 3.Department of PsychiatryUniversity Hospital MünsterMünsterGermany

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