Greater loss of 5-HT(2A) receptors in midlife than in late life

Am J Psychiatry. 2002 Mar;159(3):430-5. doi: 10.1176/appi.ajp.159.3.430.


Objective: Earlier work has shown markedly lower density of serotonin 2A (5-HT(2A)) receptors in elderly subjects than in young healthy subjects. In this study the authors used positron emission tomography (PET) and [(18)F]altanserin, a ligand with high affinity for the 5-HT(2A) receptor, to examine the relationship between 5-HT(2A) receptor density and age in more detail.

Method: The 22 subjects ranged in age from 21 to 69 years (mean=43.4, SD=13.3) and were healthy comparison subjects in a study of depression. Regions of interest were determined on magnetic resonance images and were transferred to coregistered PET data. The data were derived from dynamic PET scanning and arterial sampling with resulting plasma activity data corrected for labeled metabolites. Compartmental modeling was used to estimate the radioligand distribution volume. By comparing the distribution volume (DV) of different regions to the cerebellum distribution volume, DV(ratio)-1, which is proportional to the binding potential, was calculated.

Results: The decrease in 5-HT(2A) binding was not linear but on average was approximately 17% per decade from age 20. The correlations between age and 5-HT(2A) DV(ratio)-1 were significant for the global measure and for the medial gyrus rectus, anterior cingulate, posterior medial prefrontal cortex, hippocampus, and occipital cortex. Most of the fall off in receptor binding occurred up through midlife, and there was less decrease in late life. There were no decreases in regional brain volumes of corresponding magnitudes.

Conclusions: 5-HT(2A) receptor binding decreases dramatically in a variety of brain regions up through midlife.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging / metabolism*
  • Aging / physiology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / physiology
  • Female
  • Frontal Lobe / chemistry
  • Frontal Lobe / metabolism
  • Hippocampus / chemistry
  • Hippocampus / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Occipital Lobe / chemistry
  • Occipital Lobe / metabolism
  • Prefrontal Cortex / chemistry
  • Prefrontal Cortex / metabolism
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin / metabolism
  • Tomography, Emission-Computed


  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin