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The Journal of Neuroscience, April 26, 2006, 26(17):4638-4643; doi:10.1523/JNEUROSCI.5199-05.2006

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Neurobiology of Disease
Effects of Early Life Stress on [¹¹C]DASB Positron Emission Tomography Imaging of Serotonin Transporters in Adolescent Peer- and Mother-Reared Rhesus Monkeys

Masanori Ichise,¹ Douglass C. Vines,¹ Tami Gura,² George M. Anderson,³ Stephen J. Suomi,^4 * J. Dee Higley,^2 * and Robert B. Innis^1 *

¹Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892, ²Laboratory of Clinical Studies–Primate Unit, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland 20837, ³Departments of Child Psychiatry and Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, and ⁴Laboratory of Comparative Ethology, National Institute of Child and Human Development, National Institutes of Health Animal Center, Poolesville, Maryland 20837

Correspondence should be addressed to Dr. Masanori Ichise at his present address: Nuclear Medicine, ASBI-L1-037-E, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Email: michise{at}partners.org

Peer-reared (PR) rhesus monkeys with early maternal separation later exhibit aggressiveness, impaired impulse control, alcohol abuse, and low CSF 5-hydroxyindoleacetic acid. This study compared regional brain serotonin transporter (SERT) binding between nine PR and seven mother-reared rhesus monkeys with [¹¹C]DASB positron emission tomography (PET) imaging. Parametric images of binding potential (BP) (which is proportional to B_max/K_D, in which B_max is transporter density and K_D is dissociation constant) and relative blood flow (R₁) were generated by the two-parameter multilinear reference tissue model. R₁ images were used for coregistration and normalization of PET parametric data to the magnetic resonance imaging template space. Group BP differences were analyzed voxelwise by Student's t test in SPM2. Region of interest-based parameter values were also calculated to obtain the magnitude of regional BP differences between the two groups. For the PR group, SERT BP was decreased by 10–23% across a range of brain areas consisting of the raphe, thalamus, hypothalamus, caudate and putamen, globus pallidum, anterior cingulate gyrus, and medial temporal regions, including amygdala and hippocampus (cluster-level corrected p = 0.002). For the latter three regions, BP was decreased in the right hemisphere. These results agree with the hypothesis that early maternal deprivation affects the development of the serotonergic system and suggest that decreased serotonergic innervations in the critical brain regions may explain some of the behavioral and biochemical abnormalities in PR monkeys.

Key words: positron emission tomography; serotonin transporter; early life stress; aggression; peer-reared rhesus monkey; impulse control

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Received Dec. 6, 2005; revised Feb. 20, 2006; accepted March 27, 2006.

Correspondence should be addressed to Dr. Masanori Ichise at his present address: Nuclear Medicine, ASBI-L1-037-E, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Email: michise{at}partners.org

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