RT Journal Article
SR Electronic
T1 Cyclic AMP cascade in major depressive disorder imaged with <sup>11</sup>C-(<em>R</em>)-rolipram - Downregulation in unmedicated patients and normalization by antidepressant treatment
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 81
OP 81
VO 55
IS supplement 1
A1 Masahiro Fujita
A1 Christina Hines
A1 Sami Zoghbi
A1 Denise Rallis-Frutos
A1 Rong Xu
A1 Victor Pike
A1 Wayne Drevets
A1 Carlos Zarate
A1 Robert Innis
YR 2014
UL http://jnm.snmjournals.org/content/55/supplement_1/81.abstract
AB 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, &lt;italic&gt;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±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±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.