Background: Several lines of evidence derived from imaging and postmortem studies suggest that schizophrenia is associated with hyperactivity of dopamine function and deficiency in serotonin (5-HT) function. The aim of this study was to investigate potential alterations of striatal dopamine transporters (DAT) and brainstem serotonin transporters (SERT) density in schizophrenia.
Methods: Striatal DAT and brainstem SERT were measured in 24 patients with schizophrenia and 22 matched healthy control subjects using single photon emission computed tomography and [(123)I]beta-CIT. In this cohort of subjects, we previously reported an increase in striatal amphetamine-induced dopamine release, measured as the displacement of the D(2) receptor radiotracer [(123)I]IBZM.
Results: No differences were observed between patients and control subjects in the equilibrium uptake ratio (V(3)") of [(123)I]beta-CIT in the striatum, indicating that schizophrenia is not generally associated with an alteration of striatal DAT density; however, a trend level association (p =.07) was observed in patients with schizophrenia between low striatal [(123)I]beta-CIT V(3)" and severity of negative symptoms. After controlling for age, striatal [(123)I]beta-CIT V(3)" in patients was not associated with duration of illness, suggesting that this relative deficit was not secondary to a neurodegenerative process. No correlation was observed between DAT density and amphetamine-induced dopamine release, either in the patients or in the controls. Brainstem [(123)I]beta-CIT V(3)" was unaffected in patients with schizophrenia, and was unrelated to symptomatology.
Conclusions: Schizophrenia is generally not associated with alterations of DAT in the striatum or SERT in the brainstem. In some patients, a relative deficit in dopamine nerve terminals might play a role in the pathophysiology of negative symptoms.