title: Brain network informed subject community detection in early-onset schizophrenia.
abstract: Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.
authors.affiliation: 1] Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China [2] Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA [3] Laboratory for Functional Connectome and Development, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 1] Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China [2] Laboratory for Functional Connectome and Development, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Hoy
authors.affiliation: Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Handwerker
authors.affiliation: Scientific and Statistical Computing Core, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Mind, Brain Imaging and Neuroethics, University of Ottawa Institute of Mental Health Research, Ottawa, ON K1Z 7K4, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Northoff
authors.affiliation: 1] Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China [2] Laboratory for Functional Connectome and Development, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xi-Nian
authors.initials: XN
authors.lastname: Zuo
authors.affiliation: Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bandettini
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009415:Nerve Net / Q000503:physiopathology*; D015203:Reproducibility of Results; D012561:Schizophrenia, Childhood / Q000175:diagnosis / Q000503:physiopathology*; D013702:Temporal Lobe / Q000503:physiopathology*