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The psychotogenic effects of psychostimulant drugs have provided a major line of evidence in support of the DA hypothesis of schizophrenia. To evaluate the effects of psychostimulant (PS) drugs inschizophrenia and the clinical variables which may influence their expression, we reviewed 36 studies of PS drugs in patients with schizophrenia. Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normals. Specific clinical variables appear to modify this response, including diagnosis, degree and type of psychopathology, stage of illness and pharmacologic status at the time of testing. Non-amphetamine-like PS drugs, e.g., methylphenidate, appear to have greater psychotogenic potency than amphetamine-like PS drugs. These results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion. This biologic phenomenon may be clinically exploitable and should be investigated further.

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.