Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings

Jicai Wang, Hongbao Cao, Yanhui Liao, Weiqing Liu, Liwen Tan, Yanqing Tang, Jindong Chen, Xiufeng Xu, Haijun Li, Chunrong Luo, Chunyu Liu, Kathleen Ries Merikangas, Vince Calhoun, Jinsong Tang, Yin Yao Shugart, Xiaogang Chen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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. control. 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.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalNeuroImage: Clinical
StatePublished - 2015


  • Brain plasticity
  • Functional connectivity
  • Schizophrenia
  • Sibling controls
  • TRS

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience


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