A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity

  • Liliana Ramona Demenescu
  • Lejla Colic
  • Meng Li
  • Adam Safron
  • B. Biswal
  • Coraline Danielle Metzger
  • Shijia Li
  • Martin Walter
Original Paper


Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI’s network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate–glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic–creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.


Insula Glutamatergic metabolism Functional connectivity Depression Resting state 



This work was supported by a grant from the DFG-SFB 779 to Martin Walter. The authors will like to thank the reviewers for their constructive feedback.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Liliana Ramona Demenescu
    • 1
    • 2
  • Lejla Colic
    • 1
    • 3
  • Meng Li
    • 1
    • 2
  • Adam Safron
    • 8
  • B. Biswal
    • 9
  • Coraline Danielle Metzger
    • 4
    • 5
    • 6
    • 7
  • Shijia Li
    • 1
    • 3
    • 4
    • 10
    • 11
  • Martin Walter
    • 1
    • 2
    • 3
    • 4
    • 5
    • 12
  1. 1.Clinical Affective Neuroimaging LaboratoryMagdeburgGermany
  2. 2.Department of NeurologyOtto von Guericke UniversityMagdeburgGermany
  3. 3.Department of Behavioral NeurologyLeibniz Institute for NeurobiologyMagdeburgGermany
  4. 4.Department of Psychiatry and PsychotherapyOtto von Guericke University of MagdeburgMagdeburgGermany
  5. 5.Center for Behavioral Brain SciencesMagdeburgGermany
  6. 6.Institute of Cognitive Neurology and Dementia Research (IKND)MagdeburgGermany
  7. 7.German Center for Neurodegenerative Diseases (DZNE)MagdeburgGermany
  8. 8.Department of PsychologyNorthwestern UniversityEvanstonUSA
  9. 9.Department of Biomedical EngineeringNew Jersey Institute of TechnologyNewarkUSA
  10. 10.School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina
  11. 11.Key Laboratory of Brain Functional Genomics, Ministry of EducationShanghai Key Laboratory of Brain Functional GenomicsShanghaiChina
  12. 12.Department of PsychiatryUniversity of TuebingenTuebingenGermany

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