title: Effects of early life stress on [11C]DASB positron emission tomography imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys.
abstract: 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 Bmax/KD, in which Bmax is transporter density and KD 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.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. michise@partners.org
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Douglass C
authors.initials: DC
authors.lastname: Vines
authors.forename: Tami
authors.initials: T
authors.lastname: Gura
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Suomi
authors.forename: J Dee
authors.initials: JD
authors.lastname: Higley
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000375:Aging / Q000378:metabolism; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001010:Anxiety, Separation / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides