Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

BACKGROUND: The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. METHODS: A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (V(max)) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet V(max). RESULTS: The present study demonstrates that increases in platelet V(max) significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet V(max) is related to global DMN activation and not intrinsic DMN connectivity. CONCLUSION: This study provides evidence that platelet V(max) predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal V(max) coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.