Serotonergic Neurotransmission in Limbic Regions May Reflect Therapeutic Response of Depressive Patients: A PET Study With (11)C-WAY-100635 and (18)F-MPPF

BACKGROUND: Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. (11)C-WAY-100635 and (18)F-MPPF are positron emission tomography (PET) radioligands for 5-HT(1A) receptors. While binding of both ligands reflects 5-HT(1A) receptor density, (18)F-MPPF biding may also be affected by extracellular 5-HT concentrations. This dual-tracer PET study explored the neurochemical substrates underlying antidepressant effects in patients with depression. METHODS: Eleven patients with depression, including 9 treated with antidepressants, and 16 age- and sex-matched healthy individuals underwent PET scans with (11)C-WAY-100635 and (18)F-MPPF. Radioligand binding was determined by calculating the nondisplaceable binding potential (BP(ND)). RESULTS: Patients treated with antidepressants showed significantly lower (18)F-MPPF BP(ND) in neocortical regions and raphe nuclei, but not in limbic regions, than controls. No significant group differences in (11)C-WAY-100635 BP(ND) were found in any of the regions. Significant correlations of BP(ND) between (11)C-WAY-100635 and (18)F-MPPF were observed in limbic regions and raphe nuclei of healthy controls, but no such associations were found in antidepressant-treated patients. Moreover, (18)F-MPPF BP(ND) in limbic regions was significantly correlated with the severity of depressive symptoms. CONCLUSIONS: These results suggest a diversity of antidepressant-induced extracellular 5-HT elevations in the limbic system among depressive patients, which is associated with the individual variability of clinical symptoms following the treatment.