Introduction
The dopamine transporter regulates the reuptake of extracellular dopamine into presynaptic neurons and its dysfunction could lead to mood and behavior abnormalities as observed in bipolar disorder. Previously conducted human genetic studies have demonstrated that polymorphism of the DAT gene influences the etiology of bipolar disorder.
Objective
- To evaluate the association between bipolar disorder and dopamine transporter availability
- To assess the relationship between valproate levels and striatal dopamine transporter availability in euthymic bipolar disorder patients
Patients and Methods
Community dwelling controls (n=18) and bipolar disorder patients (n=23), aged 18-65 years in a euthymic stage who were being treated by valproate were enrolled in the study.
Assessment Parameters
- Striatal DAT availability
- Young Mania Rating Scale (YMRS)
- Hamilton Rating Scale for Depression (HDRS)
- Serum trough concentration of valproate (VPA)
Results
- The age and gender were not found to be distinctly different between the bipolar disorder patients and the controls.
- The YMRS and the HDRS scores were found to be notably higher in bipolar disorder patients as compared to the controls (p = 0.011 and p = 0.001).
- Additionally, the level of striatal dopamine transporter availability was found to be remarkably higher in the bipolar disorder patients when compared to the controls. (right: 1.53 ± 0.18 vs. 1.39 ± 0.26, p = 0.045; left: 1.52 ± 0.16 vs. 1.35 ± 0.22, p = 0.005; total: 1.52 ± 0.17 vs. 1.37 ± 0.23, p = 0.015).
- Based on the results obtained from the correlation analyses, it was found that the valproate concentration was negatively associated with the striatal dopamine transporter levels in the right (r = −0.602, p = 0.006) and the left (r = −0.652, p = 0.002) sites.
Conclusion
In patients with bipolar disorder, raised levels of striatal dopamine transporter availability was observed and it plays a crucial role in the pathophysiology of bipolar disorder impacting the valproate-mediated physiological alterations. Thus, dopamine transporter availability could be a moderator of a shared mechanism of bipolar disorder and therapeutic action of medications