American Mothers

Background. Monkeys who suffer maternal deprivation in childhood have behavioral abnormalities as adults. They tend to be fearful, more aggressive, less exploratory, and subject to binge drinking on exposure to alcohol. Prior studies showed that these monkeys have decreased levels of a metabolite of serotonin, a neurotransmitter in brain. We performed PET imaging of the serotonin transporter, a protein located on serotonin-containing nerve terminals. This transporter is the site of action of antidepressant drugs like fluoxetine (Prozac®). Consistent with the loss of serotonin metabolite in cerebrospinal fluid, adult monkeys who had suffered maternal deprivation (i.e., raised by peers), showed widespread loss of serotonin transporters in brain. We recently completed a study with this radioligand in human subjects with alcoholism (see references below) and will soon scan patients with depression in collaboration with Dr. Wayne Drevets.

Legend. Figure 1. Spatially normalized parametric images of serotonin transporter (SERT) binding potential (BP) fused onto the rhesus magnetic resonance imaging (MRI) template. BP images are shown in color while the template MRIs are shown with a gray scale. One peer-reared (PR) monkey and one mother-reared (MR) monkey are shown, respectively, in the upper half (two upper rows) and lower half (two lower rows) separated by a horizontal white line. For each monkey, coronal (top left), sagittal (top right) and transaxial (bottom left) slices are shown. The color scale on the left represents the range of BP-values from 0 to 2.4. RT = right.

Figure 2. Voxel-wise comparison of serotonin transporter (SERT) binding potential (BP) between peer-reared (PR) and mother-reared (MR) rhesus monkeys by SPM2. The panels show coronal (left top), sagittal (right top), and axial (left bottom) views of the rhesus MRI template represented with a gray scale, with superimposed p-values for a t-test (thresholded at p < 0.01, T = 2.62) representing an interconnected cluster of voxels with decreases of BP in the PR group. The color scale on the left represents the range of t-values from 0 to 4.8. RT = right.

Reference. 1.) M. Ichise, D.C. Vines, T. Gura, G.M. Anderson, S.J. Suomi, J.D. Higley, R.B. Innis. Effects of early life stress on [11C]DASB PET imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys. J. Neurosci. 26: 4638-4643, 2006. Download Reference in PDF Format (377 kb)

2) A.K. Brown, D.T. George, M. Fujita, J.-S. Liow, M. Ichise, J. Hibbeln, S. Ghose, J. Sangare, D. Hommer, and R.B. Innis. PET [11C]DASB imaging of serotonin transporters in patients with alcoholism. Alcoholism: Clin. & Exp. Res.. 31: 1-5, 2007. Download Reference in PDF