Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms

Biol Psychiatry. 1999 Oct 1;46(7):908-20. doi: 10.1016/s0006-3223(99)00152-3.


All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Brain Mapping
  • Cerebellum / physiopathology
  • Cerebral Cortex / physiopathology
  • Humans
  • Nerve Net / physiopathology
  • Neurocognitive Disorders / classification
  • Neurocognitive Disorders / diagnosis*
  • Neurocognitive Disorders / physiopathology
  • Phenotype*
  • Schizophrenia / classification
  • Schizophrenia / diagnosis*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Thalamus / physiopathology