Nancy Snidman

The Physiology and Psychology of Behavioral Inhibition in Children.

Longitudinal study of 2 cohorts of children selected in the second or third year of life to be extremely cautious and shy (inhibited) or fearless and outgoing (uninhibited) to unfamiliar events revealed preservation of these 2 behavioral qualities through the sixth year of life. Additionally, more of the inhibited children showed signs of activation in 1 or more of the physiological circuits that usually respond to novelty and challenge, namely, the hypothalamic-pituitary-adrenal axis, the reticular activating system, and the sympathetic arm of the autonomic nervous system. It is suggested that the threshold of responsivity in limbic and hypothalamic structures to unfamiliarity and challenge is tonically lower for inhibited than for uninhibited children.

Adolescent social anxiety as an outcome of inhibited temperament in childhood

OBJECTIVE Chess and Thomas suggested that temperament might make a contribution to social phobia and other forms of extreme social anxiety. This study provides the first investigation of the outcomes in adolescents who had been inhibited (subdued to and avoidant of novelty) or uninhibited (approaching novelty) in the second year of life, utilizing both direct interview and direct observation. METHOD Seventy-nine subjects, aged 13 years, who had been classified as inhibited or uninhibited in the second year were assessed with both standardized interview and direct observation. RESULTS There was a significant association between earlier classification of a child as inhibited and generalized social anxiety at adolescence, but no association with specific fears, separation anxiety, or performance anxiety. The adolescents who were classified as socially anxious made fewer spontaneous comments than those without social anxiety; no relation was seen between any other type of fear and the number of spontaneous comments. Adolescent girls who had been inhibited as toddlers were more likely to be impaired by generalized social anxiety than boys. CONCLUSIONS The interview and observational data indicate that important aspects of an inhibited temperament are preserved from the second year of life to early adolescence, which predispose an adolescent to social anxiety.

Temperamental Factors in Human Development.

The initial dispositions to approach or to avoid unfamiliar events are 2 temperamental characteristics of children--among the many that have been described--that appear to be moderately stable over time and associated with distinct, physiological profiles that may be under partial genetic control. The display of high versus low levels of both motor activity and crying to unfamiliar in 4-month-old infants predicts these 2 temperamental profiles in the 2nd year. This fact implies, but does not prove, that variation in the excitability of those brain areas that mediate motor activity and crying participates in the actualization of the temperamental categories called inhibited and uninhibited to the unfamiliar.

Early childhood predictors of adult anxiety disorders

This paper considers the influence of temperamental factors on the development of anxious symptoms in children and adolescents. About 20 percent of healthy children are born with a temperamental bias that predisposes them to be highly reactive to unfamiliar stimulation as infants and to be fearful of or avoidant to unfamiliar events and people as young children. Experiences act on this initial temperamental bias and, by adolescence, about one-third of this group is likely to show signs of serious social anxiety. These children are also likely to have one or more biological features, including a sympathetically more reactive cardiovascular system, asymmetry of cortical activation in EEG favoring a more active right frontal area, more power in the EEG in the higher frequency range, and a narrower facial skeleton. The data imply that this temperamental bias should be conceptualized as constraining the probability of developing a consistently fearless and spontaneous profile rather than as determining an anxious or introverted phenotype.

Infant Predictors of Inhibited and Uninhibited Profiles

Previous research on subjects showing the two temperamental profiles called inhibited and uninhibited to unfamiliar events suggests that the two groups differ in threshold of reactivity to novelty. Hence, variation among infants in behavioral reactivity to unfamiliar events might predict later display of the two profiles. In a longitudinal study of 94 four-month-old infants, those who displayed the combination of high motor activity and frequent crying to stimulation were more fearful to unfamiliar events at nine and 14 months than infants who displayed both low motor activity and infrequent crying. This result implies that the processes that mediate early reactivity to stimulation may also influence a later preparedness to avoid or to approach unfamiliarity.

Inhibited and uninhibited children: A follow-up study.

REZNICK, J. STEVEN; KAGAN, JEROME; SNIDMAN, NANCY; GERSTEN, MICHELLE; BAAK, KATHERINE; and ROSENBERG, ALLISON. Inhibited and Uninhibited Children: A Follow-up Study. CHILD DEVELOPMENT, 1986, 57, 660-680. A group of 46 children classified at 21 months as either behaviorally inhibited or uninhibited, and 18 children who were classified as falling at neither extreme, were observed at 5 /2years of age in contexts designed to evaluate behavior in social situations and heart rate, heart rate variability, and pupillary dilation to cognitive tasks. Additionally, 43 of the 46 inhibited or uninhibited children had been evaluated in similar contexts when they were 4 years of age. At age 51/, the formerly inhibited children, compared with the uninhibited ones, were more inhibited with peers in both laboratory and school, as well as with an adult examiner in a testing situation, and more cautious in a situation of mild risk. As at the earlier ages, more inhibited children had a relatively high and stable heart rate. The inhibited children also had tonically larger pupillary dilations to cognitive stress, were either impulsive or reflective on a test with response uncertainty, and their mothers described them as shy with unfamiliar peers. It was suggested that one or more of the stress circuits that link the hypothalamus to the pituitary, reticular activating system, and sympathetic chain are at a higher level of excitability among inhibited than among uninhibited children.

Infant temperament and anxious symptoms in school age children.

A group of 164 children from different infant temperament categories were seen at 7 years of age for a laboratory battery that included behavioral and physiological measurements. The major results indicated that children who had been classified as high reactive infants at 4 months of age, compared with infants classified as low reactive, (a) were more vulnerable to the development of anxious symptoms at age 7 years, (b) were more subdued in their interactions with a female examiner, (c) made fewer errors on a task requiring inhibition of a reflex, and (d) were more reflective. Further, the high reactives who developed anxious symptoms differed from the high reactives without anxious symptoms with respect to fearful behavior in the second year and, at age 7 years, higher diastolic blood pressure, a narrower facial skeleton, and greater magnitude of cooling of the temperature of the fingertips to cognitive challenge. Finally, variation in magnitude of interference to fearful or aggressive pictures on a modified Stroop procedure failed to differentiate anxious from nonanxious or high from low reactive children.

The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder.

BACKGROUND Behavioral inhibition to the unfamiliar (BI) is a heritable temperamental phenotype involving the tendency to display fearful, avoidant, or shy behavior in novel situations. BI is a familial and developmental risk factor for panic and phobic anxiety disorders. We previously observed an association between BI and a microsatellite marker linked to the corticotropin releasing hormone (CRH) gene in children at risk for panic disorder. To evaluate this further, we genotyped additional families for this marker and a panel of markers encompassing the CRH locus. METHODS Sixty-two families that included parents with panic disorder and children who underwent laboratory-based behavioral observations were studied. Family-based association tests and haplotype analysis were used to evaluate the association between BI and polymorphisms spanning the CRH locus. RESULTS We examined a set of markers which we found to reside in a block of strong linkage disequilibrium encompassing the CRH locus. The BI phenotype was associated with the microsatellite marker (p=.0016) and three single nucleotide polymorphisms (SNPs), including a SNP in the coding sequence of the gene (p=.023). Haplotype-specific tests revealed association with a haplotype comprising all of the markers (p=.015). CONCLUSIONS These results suggest that the CRH gene influences inhibited temperament, a risk factor for panic and phobic anxiety disorders. Genetic studies of anxiety-related temperament represent an important strategy for identifying the genetic basis of anxiety disorders.

Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition

BACKGROUND Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. METHODS We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. RESULTS We observed an association between an allele of the CRH-linked locus and BI (p =.015). Among offspring of parents with panic disorder, this association was particularly marked (p =.0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. CONCLUSIONS These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness.

Early childhood temperament as a determinant of externalizing behavior in adolescence

Two cohorts of adolescents who were categorized at either 21 or 31 months of age as extremely inhibited or uninhibited completed the Youth Self-Report (YSR), and their parents completed the Child Behavior Checklist (CBCL). In the second year, inhibited children typically cease ongoing behavior and vocalizing, seek comfort from a familiar person, or withdraw in response to unfamiliar situations. By contrast uninhibited children do not become subdued by novelty and are sociable and outgoing, often vocalizing, smiling, and approaching unfamiliar persons or objects. The 13-year-old adolescents who had been categorized as inhibited at 21 months of age scored significantly lower than adolescents originally classified as uninhibited on the Total Externalizing, Delinquent Behavior, and Aggressive Behavior Scales. Parental ratings of Total Externalizing and Aggressive behavior on the CBCL agreed with the Youth Self-Report. The second cohort of adolescents who had been selected at 31 months yielded similar findings, but only for males. These results suggest that important aspects of the original temperamental profile have been preserved over a 12-year period.