Depression and serotonin 5-HT4 receptor binding in Alzheimer's disease

Abstract

In contrast to the cholinergic system,the serotonin (5-HT) system is less studied in Alzheimer's disease (AD). The 5-HT system is, however, also affected in the course of AD. In both postmortem studies and in positron emission tomography (PET) studies, reductions in markers of pre- and postsynaptic markers have been shown. However, only few studies have been able to associate alterations in the serotonergic system inAD patients to cognitive function or depressive symptoms. The 5-HT receptor subtype 5-HT4 hasbeen linked to both cognitive function and depressive symptoms. We correlated depressive symptoms in early AD patients with 5-HT4receptorbinding in amygdala, and hypothesized that depressive symptoms would beassociated with lower 5-HT4receptor binding. Eleven patients newly diagnosed with AD (mean age 71y, range 55-85 y, six males, mean MMSE 24, range 19-27) according to the NINCDS-ADRDA criteria were recruited from the Memory Clinic at Rigshospitalet. All subjects underwent a 120 minute dynamic [11C]SB207145 PET scan. PET scans were co-registered with T1 weighted MRIs and regions were automatically delineated on each subject's MRI in auser-independent fashion. Kinetic modeling of the non-displaceable binding potential (BPND) of the 5-HT4receptor was performed with the simplified reference tissue model (SRTM) using cerebellum as reference region. Depressive symptoms were measuered by the Geriatric Depression Scale (GDS, 15-items). Correlation with BPND in amygdala was performed the Spearman rank correlation coefficient. A negative correlation was found between depression scores and BPND in amygdala, showing that lower 5-HT4 receptor was associated with more depressive symptoms (figure 1, Spearman's rho: -0.684, p < 0.029). BPND in amygdala did not correlate with age, gender, or general cognitive function (MMSE).