title: Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings.
abstract: Among individuals diagnosed with schizophrenia, approximately 20%-33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs.
  
  
  METHODS
  To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China ; Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province 650032, China.
authors.forename: Jicai
authors.initials: J
authors.lastname: Wang
authors.affiliation: Unit on Statistical Genomics, National Institute of Mental Health, NIH, Bethesda 20892, USA.
authors.forename: Hongbao
authors.initials: H
authors.lastname: Cao
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China ; Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province 650032, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province 110001, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province 650032, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of radiology, the first people's hospital of Kunming, Kunming, Yunnan province, China, 650011.
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of radiology, the first people's hospital of Kunming, Kunming, Yunnan province, China, 650011.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ries Merikangas
authors.affiliation: Mind Research Network, Albuquerque, NM 87131, USA ; Department of Electrical and Computer Engineering at the University of New Mexico, Albuquerque, NM 87106, USA.
authors.forename: Vince
authors.initials: V
authors.lastname: Calhoun
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China ; Unit on Statistical Genomics, National Institute of Mental Health, NIH, Bethesda 20892, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Unit on Statistical Genomics, National Institute of Mental Health, NIH, Bethesda 20892, USA.
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China ; State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China ; National Technology of Institute of Psychiatry, Central South University, Changsha, Hunan 410011, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D063132:Connectome / Q000145:classification*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology*; D012559:Schizophrenia / Q000503:physiopathology*; D035781:Siblings
keywords: Brain plasticity; Functional connectivity; Schizophrenia; Sibling controls; TRS