Serum prolactin response to chlorpromazine and psychopathology in schizophrenics: Implications for the dopamine hypothesis

The prolactin (PRL) response to 12.5 and 25 mg of chlorpromazine (CPZ) was studied in unmedicated schizophrenic patients and normal control subjects. Both doses produced significant increases in serum PRL levels compared to saline, but the response to 25 mg CPZ was significantly greater than that to 12.5 mg. The PRL response to the 12.5 mg dose only was significantly correlated with baseline PRL levels for both males and females, suggesting that endogenous dopamine release from tuberoinfundibular neurons has a much greater effect upon the PRL response to the 12.5 mg dose of CPZ than to the 25 mg dose. Both doses of CPZ tended to show lower PRL responses in the schizophrenic females. The PRL response to the 25 mg dose was negatively correlated with ratings of severity of delusions at the time of study. The PRL response to 25 mg correlated highly with the morning serum PRL levels following treatment with CPZ 100 mg and 200 mg orally b.i.d. for 1 week at each dose. The PRL response to both doses did not predict clinical response at the end of 2 weeks of treatment with fixed dosages of CPZ. Serum PRL levels during treatment with CPZ 200 mg b.i.d. were significantly negatively correlated with ratings of hallucinations. The negative correlations between severity of delusions and hallucinations and various PRL measures suggest that increased dopaminergic activity in the tuberoinfundibular hypothalamic-pituitary axis may be associated with increased activity of subcortical and cortical dopaminergic systems.