Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals.

Altered neurophysiological responses to emotional faces discriminate children with ASD, ADHD and ASD+ADHD.

There are high rates of overlap between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Emotional impairment in the two disorders, however, has not been directly compared using event-related potentials (ERPs) that are able to measure distinct temporal stages in emotional processing. The N170 and N400 ERP components were measured during presentation of emotional face stimuli to boys with ASD (n=19), ADHD (n=18), comorbid ASD+ADHD (n=29) and typically developing controls (n=26). Subjects with ASD (ASD/ASD+ADHD) displayed reduced N170 amplitude across all stimuli, particularly for fearful versus neutral facial expressions. Conversely, subjects with ADHD (ADHD/ASD+ADHD) demonstrated reduced modulation of N400 amplitude by fearful expressions in parietal scalp regions and happy facial expressions in central scalp regions. These findings indicate a dissociation between disorders on the basis of distinct stages of emotion processing; while children with ASD show alterations at the structural encoding stage, children with ADHD display abnormality at the contextual processing stage. The comorbid ASD+ADHD group presents as an additive condition with the unique deficits of both disorders. This supports the use of objective neural measurement of emotional processing to delineate pathophysiological mechanisms in complex overlapping disorders.

A general population twin study of conduct problems and the auditory P300 waveform.

Reduced amplitude of the P300 event-related potential has been consistently associated with a variety of externalising problems, including conduct disorder. The few available genetically-informative studies of these relationships, however, were conducted among adolescents/adults (i.e., at an age when conduct disorder has typically already become manifest). Among 200 general population twins with a mean age of 9 years (range 6-14 years), we studied the relationship between the P300 waveform elicited by an auditory oddball task and the DSM-oriented conduct problems scale of the Child Behavior Checklist 6-18. Conduct problems scores were negatively and significantly correlated (r = -0.19, p = 0.01) with P300 amplitude; correlations between P300 amplitude and the other DSM-oriented Child Behavior Checklist scales were non-significant, except for oppositional defiant problems (p = 0.01). We found moderate heritability estimates for both P300 amplitude (0.58, CI:0.37;0.73) and conduct problems (0.52, CI:0.25;0.70). Bivariate twin analyses indicated that the covariation between these two phenotypes can be explained by additive genetic factors only, with a genetic correlation of -0.33. An association between reduced P300 amplitude and conduct problems can be substantiated already in childhood, at an age that precedes the most typical onset of conduct disorder. This relationship appears to be genetic in nature. Reduced P300 amplitude can represent a valuable marker for conduct problems, and can contribute to the early identification of children at high-risk for conduct disorder.

Influence of the OPRM1 gene polymorphism upon children's degree of withdrawal and brain activation in response to facial expressions.

Genetic variation of the A118G polymorphism of the µ-opioid receptor gene (OPRM1) predicts individual sensitivity to social rejection and fMRI activation during simulated social rejection in adults, while data on these relationships during childhood are lacking. We investigated whether this polymorphism predicts childhood withdrawal - a predictor of sensitivity to social rejection -, and the face-specific N170 event-related waveform in response to facial expressions. Among facial expressions, 'anger' was expected to be particularly evocative, as it communicates social rejection. Forty-nine children aged 8-10 years were characterised for their OPRM1 genotype, their score at the Withdrawn Scale of the Child Behavior Checklist (CBCL), and for N170 latencies and amplitudes recorded during a task of implicit processing of happy, neutral, and angry expressions of other children. Children carrying the OPRM1-G allele had higher CBCL Withdrawn scores and enhanced N170 amplitudes in response to facial expressions. Multiple linear regressions showed that the Withdrawn scale score predicts larger N170 amplitudes at the Pz and C4 electrodes, only for the anger expression. Children who carry one or two copies of the OPRM1 G-allele are more likely to manifest withdrawn behaviours, and differ for electrophysiological responses to the early phases of processing affective stimuli.

Cerebral responses to emotional expressions and the development of social anxiety disorder: a preliminary longitudinal study.

BACKGROUND: Cross-sectional studies report biased reactivity to facial expressions among shy children, anxious adolescents, and adults with social anxiety disorder (SAD). It remains unknown whether cerebral reactivity to facial expressions can predict longitudinally the development of SAD in adolescence and characterize the degree of social anxiety among the general population of adolescents. METHODS: In a longitudinal study of 21 general population volunteers characterized for behavioral and genetic variables, N400 event-related potentials, and 3-Tesla fMRI activations in response to happy/neutral/angry expressions were acquired at age 8-9 and 14-15, respectively. RESULTS: By stepwise regression, N400 amplitudes acquired at age 8-9 predicted the number of DSM-IV SAD symptoms at age 14-15, with the sole, significant (P = .018) contribution of the "anger" condition. Factorial ANOVA revealed increased (Voxel-Level P((FWE)) range: .02-.0001) bilateral fMRI activations of several brain areas, including the amygdala, in response to facial expressions compared to a fixation cross. The number of symptoms of DSM-IV SAD was positively correlated with left amygdala response to angry (P((FWE)) = .036) and neutral (P((FWE)) = .025) facial expressions. Factorial ANOVA revealed that the 5-HTTLPR -S allele was associated with heightened left amygdala response to anger (P((FWE)) = .05). CONCLUSION: Cerebral reactivity to facial expressions, anger especially, measured at different developmental stages by different techniques is associated with adolescence SAD. The 5-HTTLPR genotype affects the neural processing of interpersonal affective stimuli during development.