Brain SPECT Imaging of Amphetamine-Induced Dopamine Release in Euthymic Bipolar Disorder Patients

Abstract

OBJECTIVE: Increased dopaminergic neurotransmission has been implicated in the pathophysiology of bipolar disorder. However, it remains unclear whether the abnormality is due to increased dopamine release or enhanced postsynaptic receptor sensitivity. In this study, dopamine receptor imaging combined with a pharmacological challenge of amphetamine was used to assess both pre- and postsynaptic aspects of dopamine neurotransmission in euthymic bipolar disorder patients.METHOD: Thirteen patients with bipolar disorder (seven medication free and six receiving mood stabilizer therapy) who had been euthymic for more than 4 weeks and 13 age- and gender-matched healthy comparison subjects were included in the study. Single photon emission computed tomography scans were obtained with the striatal dopamine (D₂/D₃) receptor radiotracer iodobenzamide ([¹²³I]IBZM) before and after an intravenous amphetamine challenge (0.3 mg/kg). Reduction in striatal [¹²³I]IBZM binding potential from the first scan to the second scan was used as an indirect measure of the amount of dopamine released. Behavioral response to amphetamine was measured with the Brief Psychiatric Rating Scale, Young Mania Rating Scale, and visual analogue scales.RESULTS: Bipolar patients and healthy subjects did not differ in terms of mood state or striatal D₂ receptor binding at baseline. Amphetamine challenge led to a significantly greater behavioral response in bipolar patients than in healthy subjects. However, there was no significant difference between the two groups in the amphetamine-induced decrease in striatal [¹²³I]IBZM binding.CONCLUSIONS: In a group of euthymic patients with bipolar disorder, this study did not find evidence for increased striatal dopamine release. Instead, these data are consistent with enhanced postsynaptic dopamine responsivity in patients with bipolar disorder.