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This study was begun in 1952 to test the hypothesis that specific neurointegrative disorders in infancy predict vulnerability to later schizophrenia and schizotypal disorder. Twelve offspring of chronic schizophrenic mothers and 12 controls from similar low socioeconomic status (SES) backgrounds have been studied since their births in 1952-53 and 1959-60. The infants were ranked according to the severity of their neurointegrative disorder, or "pandysmaturation" (PDM), based on analysis of Gesell tests and physical growth measures repeated 10 times between birth and 2 years. Twenty-three subjects (96 percent) completed all 10-, 15- and 20/22-year followup examinations. PDM was significantly related to maternal schizophrenia but not to obstetrical complications, SES, sex, or ethnic background. The severity of PDM was significantly related to the blind evaluations of the severity of psychopathology at 10 years. One 26-year risk subject has been chronically schizophrenic since age 17. The author, nonblind, provisionally diagnosed six other risk subjects as schizotypal or paranoid personality. All seven had PDM; six required 6 to 18+ years of treatment; four with "negative" symptoms remain severely impaired. All six sick subjects had severe social-affective symptoms by 3-6 years of age; four had perceptual deficits by 2 years. Some social-affective, cognitive, academic, and vocational impairments included in the "negative" symptoms and "process" traits of schizophrenia had antecedents before 2 years of age. Primary prevention requires research into the mechanisms underlying these dysfunctions in infancy.

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