Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: A positron emission tomography scan study

The changes in aminergic receptors elicited by antidepressant treatments ha ve been extensively examined in the brain of experimental animals using rad ioligand and molecular techniques. However, there is a very limited direct information regarding the changes effected by such treatments in the human brain, as well as its relationship to clinical improvement. Using positron emission tomography (PET) scanning, the authors examined the cortical 5-Hyd roxytryptamine-2A (5-HT2A) receptor binding of [F-18]fluoro-ethyl-spiperone after a 4-week treatment with the selective serotonin reuptake inhibitor p aroxetine. [F-18]fluoro-ethyl-spiperone labels 5-HT2A receptors in the cort ex and dopamine D-2 receptors in the basal ganglia. A binding index (BI) wa s calculated in the frontal cortex and the basal ganglia (mostly caudate-pu tamen) by reference to cerebellum. Thirty-seven inpatients with major depre ssion with a mean +/- SD score on the 21-item Hamilton Rating Scale for Dep ression (HAM-D-21) of 26.3 +/- 4.3 at admission were treated with paroxetin e 40 mg/day. After 4 weeks of treatment, the BI in the frontal cortex of re mitted patients (HAM-D-21 score = 4.7 +/- 4.0; N = 20) was significantly gr eater than the score in nonresponder patients (HAM-D-21 score = 21.2 +/- 4. 0; N = 17) (BI = 0.54 +/- 0.15 and 0.41 +/- 0.17, respectively; p < 0.02). No such difference was observed in the basal ganglia (5.45 <plus/minus> 1.1 1 and 5.39 +/- 0.82, respectively; p = 0.85). The significant difference in cortical BI persisted when age was used as covariate (p < 0.016). These da ta suggest that clinical improvement in patients treated with paroxetine is associated with an increase in the density of 5-HT2A receptors in the fron tal cortex.