To examine whether or not prolonged exposure to a depot neuroleptic has either residual or "tardive pathological" effects on normal behavior, 38 Cebus apella monkeys were observed daily for 108 weeks. The issue of stress influencing such effects was also addressed. During weeks 25-48 half of the monkeys received 0.22 mg/kg fluphenazine decanoate, IM, every 3 weeks, with the dose increased to 0.33 mg/kg during weeks 49-72. Behavioral measures were combined to form composite behavioral variables which quantify four major aspects of behavior: self- and environment-directed behavior, affiliation, aggression, and normal locomotor activity. Mean plasma fluphenazine levels at 48 h post-injection were 0.13 (+/- 0.03) ng/ml for injections 3-8 and 0.24 (+/- 0.07) ng/ml for injections 11-16. The pre-study null hypothesis that the four major aspects of behavior would not be adversely affected by this treatment during the drug-discontinuation phase of the study (weeks 73-108) was not statistically negated. There were highly significant decreases in self- and environment-directed behaviors and affiliation during the treatment periods, implying that treatment may contribute to the negative symptoms of treated schizophrenics. Stress reduced the above effects. Aggression showed some increase during early drug discontinuation, accentuated by stress. Recovery of normal (baseline) behavioral scores began by week 7 after the last treatment. Mild (bucco-lingual) tardive dyskinesias persisted in 30% of the animals for a prolonged time.

The spectral characteristics and average, auditory evoked potentials (AEPs) were determined from EEGs repeatedly recorded over a span of several years. Data from a vertex lead is presented for 4 chronic schizophrenic patients and 5 normal subjects. Measurements were made under identical conditions. For each subject characteristic spectra and AEPs were exhibited despite the passage of time. Patients had recordings performed both on and off antipsychotic medication. While receiving antipsychotic medication the patients’ EEG spectra showed an increase in alpha activity. Less consistently there was a decrease in delta or an increase in beta activity; theta activity was unchanged. These latter effects are different from those generally reported for an acute antipsychotic dose and may be more representative of antipsychotic effects (which occur after days or weeks of treatment). Psychopathology tended to be inversely related to alpha power, the magnitude of the AEP N100, and medication.

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