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The dopaminergic system has been shown to have substantial effects on the etiology of attention-deficit hyperactivity disorder (ADHD). However, while some studies found a significant direct effect, others did not. In this context, social behavior might play an important role as a factor that is related both to the dopaminergic system and ADHD. In a large epidemiological sample of adolescents (N = 462; 16–17 years), we assessed the level of ADHD symptoms using the Strengths and Difficulties Questionnaire, social behavior using the Social Responsiveness Scale, and the allelic distribution of the dopaminergic catechol-O-methyltransferase (COMT) Val158Met polymorphism. We found a significant association between COMT and social impairment, insofar as Met-allele carriers showed increased levels of social impairment. Moreover, social impairment significantly determined an association between COMT and ADHD (explained variance: 19.09%). This effect did not significantly differ between males and females. COMT and social impairment might interactively affect ADHD symptomatology, and could thus represent significant gene-phenotypic risk factors for ADHD symptomatology. This might have interesting implications for prevention and intervention strategies with a focus on social behavior in genetically at-risk individuals.

Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2) = 0.38, p

The precise effects of normal aging on the cholinergic system are unknown, as both in vitro and PET studies have shown conflicting results. In vivo determination of muscarinic receptor distribution and density has been hampered by both poor subtype selectivity and/or blood–brain barrier permeability of known ligands. Previous in vitro and in vivo work with the F-18 labeled muscarinic agonist, 3-(3- (3-[18F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (18FP-TZTP) suggested the use of 18FP-TZTP to selectively quantify M2 receptors in humans. In this study, we used 18FP-TZTP to infer M2 receptor avidity in the brains of 15 healthy younger subjects (mean age = 28.3 ± 5.5 years) and 20 healthy older subjects (mean age = 62.1 ± 7.7 years). Corrections for subject motion during the 120-min acquisition and partial voluming (PVC) were performed. A one-tissue compartment model was used to estimate the volumes of distribution (VT) of 18FP-TZTP. Within both groups of subjects, volumes of distribution (K1/k2) in cortical, subcortical, and cerebellar areas were consistent with M2 receptor topography. Compared to younger subjects older subjects had significantly higher means and standard deviations for the volumes of distribution of 18FP-TZTP throughout much of the cerebellum, cortex, and subcortex (Global Gray VT = 742 ± 163 in older subjects and 645 ± 74 in younger subjects, P < 0.03). Across all subjects 18FP-TZTP, regional, and Global Gray distribution volumes were significantly correlated to age (Global Gray VT, r = 0.41, P < 0.01). A lower concentration of acetylcholine in the synapse of some older subjects is one possible explanation for the data. Synapse 48:39–44, 2003. Published 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]