Attenuated resting-state functional connectivity in patients with childhood- and adult-onset schizophrenia

Schizophr Res. 2018 Jul;197:219-225. doi: 10.1016/j.schres.2018.01.003. Epub 2018 Jan 6.


Background: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset disorder (AOS). Our previous resting-state fMRI study identified attenuated functional connectivity in COS compared with controls. Here, we ask whether COS and AOS patients and their siblings exhibit similar abnormalities of functional connectivity.

Methods: A whole-brain, data-driven approach was used to assess resting-state functional connectivity differences in COS (patients/siblings/controls, n: 26/28/33) and AOS (n: 19/28/30). There were no significant differences in age, sex, or head motion across groups in each dataset and as designed, the COS dataset has a significantly lower age than the AOS.

Results: Both COS and AOS patients showed decreased functional connectivity relative to controls among a wide set of brain regions (P<0.05, corrected), but their siblings did not. Decreased connectivity in COS and AOS patients showed no amplitude differences and was not modulated by age-at-onset or medication doses. Cluster analysis revealed that these regions fell into two large-scale networks: one sensorimotor network and one centered on default-mode network regions, but including higher-order cognitive areas only in COS. Decreased connectivity between these two networks was notable (P<0.05, corrected) for both patient groups.

Conclusions: A shared pattern of attenuated functional connectivity was found in COS and AOS, supporting the continuity of childhood-onset and adult-onset schizophrenia. Connections were altered between sensorimotor areas and default-mode areas in both COS and AOS, suggesting potential abnormalities in processes of self-monitoring and sensory prediction. The absence of substantial dysconnectivity in siblings indicates that attenuation is state-related.

Keywords: Childhood psychosis; Network connectivity; Neurodevelopment.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Connectome*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / physiopathology*
  • Siblings
  • Young Adult