Association of intellectual impairment, negative symptoms, and aging with tardive dyskinesia: clinical and animal studies.

It is not known why some schizophrenic patients receiving long-term neuroleptic treatment develop abnormal involuntary orofacial movements, while others do not. Schizophrenic patients with orofacial dyskinesia were found to be more intellectually impaired, more likely to show negative symptoms, and older than those without such movements. These features are characteristic of the "defect state," wherein structural brain changes may be demonstrable. Prolonged long-term neuroleptic treatment of young rats was associated with late-onset orofacial movements; however, such movements occurred spontaneously in untreated senescent rats. Structural brain changes consequent to aging and disease processes may be associated with the emergence of orofacial dyskinesia, even in the absence of exposure to neuroleptics. These movements do not appear to have their basis in striatal dopamine receptor supersensitivity.