Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT

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 [123I]β-CIT. In this cohort of subjects, we previously reported an increase in striatal amphetamine-induced dopamine release, measured as the displacement of the D2 receptor radiotracer [123I]IBZM. Results: No differences were observed between patients and control subjects in the equilibrium uptake ratio (V3″) of [123I]β-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 [123I]β-CIT V3″ and severity of negative symptoms. After controlling for age, striatal [123I]β-CIT V3″ 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 [123I]β-CIT V3″ 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.