Cognitive function and 5-HT2A receptors in healthy volunteers, an [18F]altanserin PET study

Abstracts / NeuroImage 41 (2008) T58–T200

T159

Poster Presentation No.: P098

Cognitive function and 5-HT2A receptors in healthy volunteers, an [ 18 F]altanserin PET study Karine Madsen,a D. Erritzøe,a L. Marner,a A. Gade,b G.M. Knudsen,a and S.G. Hasselbalcha,c a

b

Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark Department of Psychology, University of Copenhagen, Copenhagen, Denmark c The Memory Clinic, Rigshospitalet, Copenhagen, Denmark

Introduction: Manipulation studies of central serotonergic activity in healthy volunteers have indicated that long-term memory and executive functions are the cognitive domains most sensitive to manipulations. However, only few PET serotonin studies have involved cognitive research in healthy volunteers. The aim was to evaluate the correlations between performance in sensitive cognitive tests in young healthy volunteers with regional 5-HT2A receptor levels. A negative correlation was hypothesized. Methods: 33 healthy volunteers (mean age 25.6, range 19–37 years, mean BMI 25.2, range 19.3–41.5, 25 males) were included. The 5-HT2A binding was imaged with [18F]altanserin PET in a GE Advance scanner. A 40 min scan was acquired in steady-state conditions. Volumes of interest were delineated automatically on coregistered 3T T1-weighted magnetic resonance images. Regional partial volume corrected binding potentials, BPP, were calculated for the bilateral prefrontal cortex and mesial temporal cortex (containing hippocampus and enthorinal cortex) using cerebellum as a reference region and metabolite corrected venous plasma concentration. Long time memory was measured with a 30 min delayed recall of Rey Auditory Verbal Learning Test and a 3 min recall of Rey's Complex Figure. Executive function was measured with Trail Making B test and Stroop Color Word Test incongruent version. Intelligence was measured with The Danish Adult Reading Test (DART45) and educational level was scored. All correlations were calculated with BMI as a co-variate, which significantly influenced on BPp. Results: No correlations between the specific memory and executive function tests and regional BPP were found. In post hoc analysis, both prefrontal and mesial temporal BPP correlated negatively with performance of DART45 (p = 0.023 and p = 0.011). Mesial temporal BPP also showed a tendency to a negative correlation with educational level (p = 0.060). A negative correlation was also found between BPP in a global neocortical region and DART45 (p = 0.025), and again a tendency was found for educational level (p = 0.094). All p-values are uncorrected. Conclusion: Our results showed a negative correlation between 5-HT2A binding and intelligence, and a tendency was found for educational level. The findings should be corroborated with more comprehensive tests for intelligence. A specific link between the 5-HT2A receptor level and cognitive performance is supported by changed 5-HT2A receptor levels found in diseases involving cognitive dysfunction, such as depression and Alzheimer's disease. Alternatively, a high serotonergic tone may lead to a down-regulation of 5-HT2A receptor level in the young intelligent and well educated subjects. The specific tests for memory and executive function did not correlate with the 5-HT2A binding, indicating that a putative link between the 5-HT2A receptor level and general intelligence must be mediated through other mechanisms than mere memory and executive functions. doi:10.1016/j.neuroimage.2008.04.126