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

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicate d 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 het erogeneous and nor a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single dis order linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for d isruption in a specific circuit is explored: the cortical-thalamic-cerebell ar-cortical circuit (CCTCC), It is suggested that a disruption in this circ uit leads to an impairment in synchrony, or the smooth coordination of ment al processes, When synchrony. is impaired, the patient suffers from a cogni tive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms. Biol Psychiatry 1999;46:908-920 (C) 1999 Society of Biological Psychiatry.