@article {Fujita81, author = {Masahiro Fujita and Christina Hines and Sami Zoghbi and Denise Rallis-Frutos and Rong Xu and Victor Pike and Wayne Drevets and Carlos Zarate and Robert Innis}, title = {Cyclic AMP cascade in major depressive disorder imaged with 11C-(R)-rolipram - Downregulation in unmedicated patients and normalization by antidepressant treatment}, volume = {55}, number = {supplement 1}, pages = {81--81}, year = {2014}, publisher = {Society of Nuclear Medicine}, abstract = {81 Objectives Rat and human postmortem studies indicated that the cAMP cascade is downregulated in major depressive disorder (MDD) and that antidepressant treatment normalizes this change. Rolipram, a selective inhibitor of phosphodiesterase-4 (PDE4), has been labeled with carbon-11 for PET imaging. We previously showed that unmedicated patients with MDD have lower rolipram binding indicating downregulation of the cAMP cascade (Biol Psychiat. 72:548). The current study aimed to compare rolipram binding before and after selective serotonin-reuptake inhibitor (SSRI) therapy in MDD patients and also to compare rolipram binding between healthy controls and unmedicated patients with a larger sample size in each group than that in our published study. Methods Thirty five healthy controls and 40 unmedicated MDD patients were studied. Twenty of the MDD patients had a repeat scan ~8 weeks after SSRI treatment. Eleven healthy controls had a repeat scan without SSRI. Total distribution volume normalized to plasma free fraction, \<italic\>Vx003E;T/fP of 11C-(R)-rolipram, was measured in 10 regions throughout the brain using unconstrained two-compartment model and metabolite-corrected arterial input function. Results Unmedicated patients showed lower 11C-(R)-rolipram binding than controls in all regions with an average change of -18\% (p=0.002). Twenty patients, scanned a second time with 11C-(R)-rolipram during SSRI treatment, showed an increase of 14{\textpm}38\% binding across all brain regions (p=0.001 when age was used as a covariate). In contrast, eleven healthy controls showed similar binding on repeat scans, which changed by only -2{\textpm}13\%. Conclusions Consistent with the cAMP theories of depression and of antidepressant action, radioligand binding to PDE4 was downregulated in unmedicated patients and increased / normalized after ~8 weeks treatment with an SSRI.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/55/supplement_1/81}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }