PET Imaging of Serotonin Type 2A Receptors in Late-Life Neuropsychiatric Disorders

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT_2A) receptor in late-life depression and Alzheimer’s disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [¹⁸F]altanserin to evaluate 5-HT_2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age=65.0 years, SD=5.5); nine Alzheimer’s disease patients, including three with concurrent depression (two men, seven women; mean age=69.7 years, SD=5.0); and 10 age-matched healthy subjects (four men, six women; mean age=69.8 years, SD=5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [¹⁸F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alz­heimer’s disease group. However, the patients with Alzheimer’s disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT_2A receptor is differentially affected in late-life depression and Alzheimer’s disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.