Heather A. Henderson

Stable early maternal report of behavioral inhibition predicts lifetime social anxiety disorder in adolescence.

OBJECTIVE Behavioral inhibition (BI), a temperamental style identifiable in early childhood, is considered a risk factor for the development of anxiety disorders, particularly social anxiety disorder (SAD). However, few studies examining this question have evaluated the stability of BI across multiple developmental time points and followed participants into adolescence-the developmental period during which risk for SAD onset is at its peak. The current study used a prospective longitudinal design to determine whether stable early BI predicted the presence of psychiatric disorders and continuous levels of social anxiety in adolescents. It was hypothesized that stable BI would predict the presence of adolescent psychiatric diagnoses, specifically SAD. METHOD Participants included 126 adolescents aged 14 to 16 years who were first recruited at 4 months of age from hospital birth records. Temperament was measured at multiple time points between the ages of 14 months and 7 years. In adolescence, diagnostic interviews were conducted with parents and adolescents, and continuous measures of adolescent- and parent-reported social anxiety were collected. RESULTS Stable maternal-reported early BI was associated with 3.79 times increased odds of a lifetime SAD diagnosis, but not other diagnoses, during adolescence (95% confidence interval 1.18-12.12). Stable maternal-reported early BI also predicted independent adolescent and parent ratings of ongoing social anxiety symptoms. CONCLUSIONS Findings suggesting that stable maternal-reported early BI predicts lifetime SAD have important implications for the early identification and prevention of SAD.

Evidence for a gene-environment interaction in predicting behavioral inhibition in middle childhood

Gene-environment interactions are presumed to shape human behavior during early development. However, no human research has demonstrated that such interactions lead to stable individual differences in fear responses. We tested this possibility by focusing on a polymorphism in the promoter region of the gene for the serotonin transporter (5-HTT). This polymorphism has been linked to many indices of serotonin activity. Specifically, we tested the hypothesis that an interaction between childrens 5-HTT status and maternal reports of social support predicts inhibited behavior with unfamiliar peers in middle childhood. Results were consistent with this hypothesis: Children with the combination of the short 5-HTT allele and low social support had increased risk for behavioral inhibition in middle childhood.

Attention Alters Neural Responses to Evocative Faces in Behaviorally Inhibited Adolescents

Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N=10, mean 12.8 years) and BN (N=17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety.

A history of childhood behavioral inhibition and enhanced response monitoring in adolescence are linked to clinical anxiety.

BACKGROUND Behaviorally inhibited (BI) children who also exhibit enhanced response monitoring might be at particularly high risk for anxiety disorders. The current study tests the hypothesis that response monitoring, as manifest in the error-related negativity (ERN), moderates the association between BI and anxiety. METHODS Participants (n=113; 73 male) assessed for early-childhood BI were re-assessed as adolescents with a clinical interview and a flanker paradigm that generated behavioral data and event-related potentials (ERPs). Risk for anxiety disorders in adolescents was examined as a function of childhood-BI status and adolescent performance on the flanker paradigm. RESULTS Adolescents with childhood BI displayed ERP evidence of enhanced response monitoring, manifest as large ERNs. The ERN moderated the relationship between early BI and later clinically significant disorders. CONCLUSIONS Physiological measures of response monitoring might moderate associations between early-childhood BI and risk for psychopathology. The subset of children with BI and enhanced response monitoring might face greater risk for later-life clinical anxiety than children with either BI or enhanced response monitoring alone.

Behavioral Reactivity and Approach-Withdrawal Bias in Infancy.

Seven hundred seventy-nine infants were screened at 4 months of age for motor and emotional reactivity. At age 9 months, infants who showed extreme patterns of motor and negative (n = 75) or motor and positive (n = 73) reactivity and an unselected control group (n = 86) were administered the Laboratory Temperament Assessment Battery, and baseline electroencephalogram data were collected. Negatively reactive infants showed significantly more avoidance than positively reactive infants and displayed a pattern of right frontal electroencephalogram asymmetry. Positively reactive infants exhibited significantly more approach behavior than controls and exhibited a pattern of left frontal asymmetry. Results support the notion that approach-withdrawal bias underlies reactivity in infancy.

Response monitoring, the error-related negativity, and differences in social behavior in autism

Children with autism not only display social impairments but also significant individual differences in social development. Understanding the source of these differences, as well as the nature of social impairments, is important for improved diagnosis and treatments for these children. Current theory and research suggests that individual differences in response monitoring, a specific function of the anterior cingulate cortex (ACC), may contribute to social-emotional and social-cognitive impairments and individual differences in autism. To examine this hypothesis, we used a modified flanker task to assess an ERP index of response monitoring, the error-related negativity (ERN), in a sample of higher function children with autism (HFA) and an IQ-matched control sample. The results revealed a significant Diagnostic group by Verbal IQ interaction on ERN amplitude indicating that the most verbally capable HFA children displayed significantly larger ERN amplitudes than did the control children. Within the HFA sample, greater ERN amplitude was also related to parent reports of fewer symptoms of social interaction impairments, fewer internalizing problems, but more externalizing problems, although these associations were reduced to nonsignificance when medication status was controlled. The latter results complement previous observations from imaging studies of a significant association between ACC activity and social symptoms and impairments in autism. The implications of these results for future research on brain-behavior relations, as well as treatment related research with children with autism are discussed.

Longitudinal Stability of Temperamental Exuberance and Social-Emotional Outcomes in Early Childhood

The goals of the current study were to investigate the stability of temperamental exuberance across infancy and toddlerhood and to examine the associations between exuberance and social-emotional outcomes in early childhood. The sample consisted of 291 4-month-olds followed at 9, 24, and 36 months and again at 5 years of age. Behavioral measures of exuberance were collected at 9, 24, and 36 months. At 36 months, frontal electroencephalogram (EEG) asymmetry was assessed. At 5 years, maternal reports of temperament and behavior problems were collected, as were observational measures of social behavior during an interaction with an unfamiliar peer in the laboratory. Latent profile analysis revealed a high, stable exuberance profile that was associated with greater ratings of 5-year externalizing behavior and surgency, as well as observed disruptive behavior and social competence with unfamiliar peers. These associations were particularly true for children who displayed left frontal EEG asymmetry. Multiple factors supported an approach bias for exuberant temperament but did not differentiate between adaptive and maladaptive social-emotional outcomes at 5 years of age.

Developmental and Individual Differences on the P1 and N170 ERP Components in Children With and Without Autism

The P1 and N170 components, two event-related potentials sensitive to face processing, were examined in response to faces and vehicles for children with autism and typical development. P1 amplitude decreased, P1 latency decreased, and N170 amplitude became more negative with age. Children with typical development had larger P1 amplitudes for inverted faces than upright faces, but children with autism did not show this pattern. Children with autism had longer N170 latencies than children with typical development. Smaller P1 amplitudes and more negative N170 amplitudes for upright faces were associated with better social skills for children with typical development.

Startle Response in Behaviorally Inhibited Adolescents With a Lifetime Occurrence of Anxiety Disorders

OBJECTIVE Behaviorally inhibited children face increased risk for anxiety disorders, although factors that predict which children develop a disorder remain poorly specified. The current study examines whether the startle reflex response may be used to differentiate between behaviorally inhibited adolescents with and without a history of anxiety. METHOD Participants were assessed for behavioral inhibition during toddlerhood and early childhood. They returned to the laboratory as adolescents and completed a fear-potentiated startle paradigm and a clinical diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). Magnitude of the startle reflex was examined at baseline and during cues associated with safety and threat. RESULTS Only adolescents who showed high levels of behavioral inhibition and had a lifetime occurrence of anxiety disorders showed increased startle reactivity in the presence of safety cues. Neither behavioral inhibition nor diagnosis was related to startle reactivity during threat cues. CONCLUSIONS These results suggest that neurobiological measures, such as the startle reflex, may be a potential risk marker for the development of anxiety disorders among behaviorally inhibited adolescents. These methods may enhance our ability to identify vulnerable individuals before the development of anxious psychopathology.

Self-referenced processing, neurodevelopment and joint attention in autism

This article describes a parallel and distributed processing model (PDPM) of joint attention, self-referenced processing and autism. According to this model, autism involves early impairments in the capacity for rapid, integrated processing of self-referenced (proprioceptive and interoceptive) and other-referenced (exteroceptive) information. Measures of joint attention have proven useful in research on autism because they are sensitive to the early development of the ‘parallel’ and integrated processing of self- and other-referenced stimuli. Moreover, joint attention behaviors are a consequence, but also an organizer of the functional development of a distal distributed cortical system involving anterior networks including the prefrontal and insula cortices, as well as posterior neural networks including the temporal and parietal cortices. Measures of joint attention provide early behavioral indicators of atypical development in this parallel and distributed processing system in autism. In addition it is proposed that an early, chronic disturbance in the capacity for integrating self- and other-referenced information may have cascading effects on the development of self awareness in autism. The assumptions, empirical support and future research implications of this model are discussed.