Disturbed Functional Connectivity Between Anterior Default Mode and Sensory Processing Regions Is Linked to Peripheral Inflammatory Markers and Psychopathology in Schizophrenia

Schizophrenia Bulletin, vol. 52

Abstract

BACKGROUND AND HYPOTHESIS: Both elevated inflammatory markers and aberrant functional connectivity have been detected in patients with schizophrenia, but there is limited knowledge on the relationship between the two phenomena. Some positive symptoms may arise from external misattribution of self-generated actions mediated by decoupling of the default mode network (DMN) with sensory processing regions. Since the anterior DMN also exhibits bidirectional interaction with the immune system, we hypothesized its decoupling would be associated with elevated inflammatory markers as well as the burden of positive symptomatology. STUDY DESIGN: Resting-state functional magnetic resonance imaging, diffusion tensor imaging (DTI), clinical and laboratory data (serum concentrations of interleukin-6 and C-reactive protein) were collected within a neuroimaging trial on schizophrenia. Neuroimaging data were assessed applying seed-to-voxel and region-of-interest-to-region-of-interest functional connectivity analyses as well as DTI tractography. Associations between neuroimaging and laboratory as well as behavioral data were studied employing regression analyses. STUDY RESULTS: For both inflammatory markers, a consistent pattern of hypo-connectivity emerged between the anterior DMN and different brain regions involved in sensory processing and self-monitoring. The strongest association was detected for the connectivity between the anterior DMN and the right parietal operculum which was not explained by the structural integrity of the respective white matter tract. Finally, this functional connection was correlated both with the burden of positive and negative symptoms. CONCLUSIONS: Our findings reveal a mechanistically plausible neurobiological link between inflammation and psychopathology in schizophrenia.

Authors 9

1. Emanuel Mlynek Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,

2. Xiaolin Tan corresponding

   Sheng Jing Hospital · China Medical University

   Affiliation as printed

   Shengjing Hospital of China Medical University , Shenyang 110004 ,

3. Sarah Edith Lammertz Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,

4. Sabrina Schaffrath Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,

5. Gerhard Gründer

   Heidelberg University · Central Institute of Mental Health · Medizinische Fakultät Mannheim

   Affiliation as printed

   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg , Mannheim 68159 ,

6. Frank W. Schneider

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of the History, Philosophy and Ethics of Medicine, Centre for Health and Society, Heinrich-Heine-University , Düsseldorf 40225 ,

7. Thomas Frodl Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University · Otto-von-Guericke-Universität Magdeburg

   Affiliation as printed

   Department of Psychiatry and Psychotherapie, Otto von Guericke University , Magdeburg 39120 ,

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,

8. Klaus Mathiak Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,

9. Arnim Johannes Gaebler Aachen Department of Neurophysiology Faculty of Medicine Department of Psychiatry, Psychotherapy and Psychosomatics

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen , Aachen 52074 ,

   JARA Translational Brain Medicine , Aachen 52074 ,