title: Disruptions in the left frontoparietal network underlie resting state endophenotypic markers in schizophrenia.
abstract: Advances in functional brain imaging have improved the search for potential endophenotypic markers in schizophrenia. Here, we employed independent component analysis (ICA) and dynamic causal modeling (DCM) in resting state fMRI on a sample of 35 schizophrenia patients, 20 first-degree relatives and 35 control subjects. Analysis on ICA-derived networks revealed increased functional connectivity between the left frontoparietal network (FPN) and left temporal and parietal regions in schizophrenia patients (P < 0.001). First-degree relatives shared this hyperconnectivity, in particular in the supramarginal gyrus (SMG; P = 0.008). DCM analysis was employed to further explore underlying effective connectivity. Results showed increased inhibitory connections to the left angular gyrus (AG) in schizophrenia patients from all other nodes of the left FPN (P < 0.001), and in particular from the left SMG (P = 0.001). Relatives also showed a pattern of increased inhibitory connections to the left AG (P = 0.008). Furthermore, the patient group showed increased excitatory connectivity between the left fusiform gyrus and the left SMG (P = 0.002). This connection was negatively correlated to inhibitory afferents to the left AG (P = 0.005) and to the negative symptom score on the PANSS scale (P = 0.001, r = -0.51). Left frontoparietotemporal dysfunction in schizophrenia has been previously associated with a range of abnormalities, including formal thought disorder, working memory dysfunction and sensory hallucinations. Our analysis uncovered new potential endophenotypic markers of schizophrenia and shed light on the organization of the left FPN in patients and their first-degree relatives. Hum Brain Mapp 38:1741-1750, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany.|Department of Psychiatry, Maimonides Medical Center, Brooklyn, New York.
authors.forename: George
authors.initials: G
authors.lastname: Chahine
authors.affiliation: Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Richter
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wolter
authors.affiliation: Department of Psychiatry and Psychotherapy, Centre for Translational Research in Systems, Neuroscience and Clinical Psychiatry, George August University, Göttingen, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Goya-Maldonado
authors.affiliation: Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000328:Adult; D058068:Endophenotypes; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017711:Nonlinear Dynamics; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012146:Rest; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*
chemical_list: D010100:Oxygen
keywords: biomarker; endophenotypes; neuroimaging; schizophrenia