Introduction
The dopamine transporters (DATs) and dopamine D2/D3 receptors are implicated in a variety of neuropsychiatric disorders. Both sites are also targets for drug treatment. Previous single photon emission computed tomography (SPECT) studies have demonstrated that co-injection of radioligand [99mTc]TRODAT for DAT and 123I-labeled iodobenzamide (123IBZM) for D2/D3 receptors image can assess both pre- (DATs) and postsynaptic sites (D2/D3 receptors) of the dopaminergic system simultaneously. The aim of this study was to measure both pre and post markers of dopaminergic system in drug naïve schizophrenia.
Methods
Seven drug naïve schizophrenia and eleven age-matched healthy controls were recruited. Each subject received one SPECT examination after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT and 185 MBq (5 mCi) [123IBZM]. SPECT data were acquired by a dual head gamma camera equipped with ultra-high resolution fan beam collimators. An equilibrium ratio model was used for data analysis. Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10% asymmetric with a lower bound at 159 keV for 123I. Region of interest (ROI) analysis method was performed using predefined templates from magnetic resonance image (MRI). Cerebellum was used as a reference region.
Results
The major findings including
DATs binding had no significant changes between controls and schizophrenia (3. 17±0.73 vs. 2.65±0.27, p=0.052). However, D2/D3 receptors binding was significantly lower in drug naïve schizophrenia than those in controls (3.90±0.58 vs. 2.79±0.54, p=0.001). There was a well correlation of left to right binding for both DATs and D2/D3 receptors in controls (Pearson's correlation coefficient (pcc)=0.80, p=0.003 for DATs, 0.96, p=0.000 for D2/D3 receptors) but the left to right correlation was disappeared in schizophrenia (pcc=0.54, p=0.20 for DATs, 0.70, p=0.08 for D2/D3 receptors). The asymmetric indices of post to pre binding were 0.15±0.12 in controls (p=0.002, one sample t-test) and 0.02±0.12 in schizophrenia (p=0.67, one sample t-test).
Conclusion
This study clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic binding sites of the dopaminergic system in drug naïve schizophrenia with dual-isotope SPECT technique. The abnormalities of D2/D3 receptor binding support the dopamine hypothesis and further elucidate that schizophrenia might be a disease with postsynaptic but not presynaptic disturbance.