Age decline in the subcortical 5-HT6 receptor as imaged in male volunteers

Objectives Previous imaging studies have suggested an age-related decline in brain serotonin (5-hydroxytryptamine or 5-HT) measures in healthy subjects. This project seeks to investigate via positron emission tomography (PET) imaging whether the availability of 5-HT6 is also changed with age.

Methods Twenty-nine healthy control subjects (all males; mean age 36±9; range 23-52 years) were scanned with the PET radiotracer [11C]GSK215083 that exhibits high binding affinity for the 5-HT6 receptor specifically localized in the striatum. Dynamic PET scans were acquired on the Siemens HR+. An early summed PET image was created and registered to the subject’s 3T MR anatomical image (6-parameter affine registration) which was then registered to an MR template using a non-linear transform with Bioimagesuite. Automatic regions-of-interest (Anatomical Automatic Labeling (AAL) for SPM2) were then applied to generate time-activity curves (TACs) in the striatum (caudate and putamen). The 90-min TACs were fitted with the MA1 (t*=40) model with a metabolite-corrected arterial input function, and regional binding potential (BPND) was calculated from the fitted VT values using the cerebellum as the reference region.

Results Regional [11C]GSK215083 BPND displayed a negative correlation with age in the caudate (r = -0.51, P = 0.005) and putamen (r = -0.46, P = 0.01). 5-HT6 receptor availability in these two brain regions were found to be 22% (caudate) and 13% (putamen) lower with each decade of life studied.

Conclusions PET imaging studies with [11C]GSK215083 infer an age-related decrease in 5-HT6 receptors in the striatum of healthy males. These findings indicate that age is a relevant factor to take into account when studying potential 5-HT6 receptor alterations in psychiatric disorders.