An abnormal relation between basal prolactin levels and prolactin response to 12.5µg TRH i.v. in drug-naïve patients with first-episode schizophrenia

Abstract 

At doses lower than those needed to stimulate prolactin release directly, TRH almost completely antagonizes the inhibitory effect of dopamine on prolactin release. We have previously reported that prolactin response to administration of 12.5µg TRH i.v. correlates with prolactin response to 0.5mg i.m. haloperidol and negatively with 24-h urinary excretion of HVA in normal subjects, suggesting that the response reflects dopamine activity. An association between central dopamine hyperactivity and SANS scores relating to poverty of content of speech and inattention has been suggested by studies utilizing methylphenidate administration in patients with first-episode schizophrenia. The hypothesis that small plasma prolactin responses to administration of 12.5µg TRH i.v. (∆ prolactin) correlate with SANS scores for these symptoms was tested in 19 drug-naïve patients with first-episode schizophrenia. Significant negative correlations were found between the response and scores relating to poverty of content of speech (r=−0.55, p=0.014) and inattention (r=−0.52, p=0.022), supporting the hypothesis of increased dopamine activity in association with disorganization symptoms. A significant positive correlation between basal prolactin levels and prolactin response to stimulation by 12.5µg TRH was also found (r=+0.61, p=0.0058). Our previous study in normal subjects found a similar positive correlation between basal prolactin levels and prolactin response to stimulation by 200µg TRH i.v., but not by 12.5µg TRH i.v. As far as we know, this is the first study to report an abnormality in TRH-induced prolactin release in acute schizophrenia.

Keywords: TRH, Prolactin, Schizophrenia, Dopamine, Disorganization