Translocator Protein Distribution Volume Predicts Reduction Of Symptoms During Open-Label Trial Of Celecoxib In Major Depressive Disorder

BACKGROUND: Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO V-T), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO V-T in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder.METHODS: A total of 41 subjects with treatment-resistant major depressive disorder underwent one [F-18]FEPPA positron emission tomography scan to measure PFC and ACC TSPO V-T. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS).RESULTS: Cumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO V-T, showing a significant nonlinear relationship. At low TSPO V-T values, there was no reduction in HDRS scores, but as TSPO V-T values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO V-T accounted for 84% and 92% of the variance, respectively.CONCLUSIONS: Celecoxib administration in the presence of gliosis labeled by TSPO V-T is associated with greater reduction of symptoms. Given the predictiveness of TSPO V-T on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.