title: A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.
abstract: 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.
authors: Clinical Affective Neuroimaging Laboratory, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Neurology, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Liliana Ramona
authors: LR
authors: Demenescu
authors: Clinical Affective Neuroimaging Laboratory, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany.
authors: Lejla
authors: L
authors: Colic
authors: Clinical Affective Neuroimaging Laboratory, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Neurology, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Meng
authors: M
authors: Li
authors: Department of Psychology, Northwestern University, Evanston, IL, 60208, USA.
authors: Adam
authors: A
authors: Safron
authors: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.
authors: B
authors: B
authors: Biswal
authors: Department of Psychiatry and Psychotherapy, Otto von Guericke University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.|Center for Behavioral Brain Sciences, Leipziger Str. 44, 39120, Magdeburg, Germany.|Institute of Cognitive Neurology and Dementia Research (IKND), Leipziger Str. 44, 39120, Magdeburg, Germany.|German Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, 39120, Magdeburg, Germany.
authors: Coraline Danielle
authors: CD
authors: Metzger
authors: Clinical Affective Neuroimaging Laboratory, Leipziger Str. 44, 39120, Magdeburg, Germany.|Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany.|Department of Psychiatry and Psychotherapy, Otto von Guericke University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.|School of Psychology and Cognitive Science, East China Normal University, Shanghai, China.|Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Shanghai, China.
authors: Shijia
authors: S
authors: Li
authors: Clinical Affective Neuroimaging Laboratory, Leipziger Str. 44, 39120, Magdeburg, Germany. martin.walter@uni-tuebingen.de.|Department of Neurology, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany. martin.walter@uni-tuebingen.de.|Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118, Magdeburg, Germany. martin.walter@uni-tuebingen.de.|Department of Psychiatry and Psychotherapy, Otto von Guericke University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany. martin.walter@uni-tuebingen.de.|Center for Behavioral Brain Sciences, Leipziger Str. 44, 39120, Magdeburg, Germany. martin.walter@uni-tuebingen.de.|Department of Psychiatry, University of Tuebingen, Calwerstrasse 24, 72072, Tuebingen, Germany. martin.walter@uni-tuebingen.de.
authors: Martin
authors: M
authors: Walter
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D063132:Connectome / Q000379:methods*; D003401:Creatine / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D003401:Creatine
keywords: Depression; Functional connectivity; Glutamatergic metabolism; Insula; Resting state