Is behavioral inhibition related to the anxiety disorders?

Clinical Psychology Review, Vol. 16, No. 2, pp. 157-172, 1996 Copyright 0 1996 Elsetier Science Ltd Printed in the USA. All rights reserved 02%7358/!36 $15.00 + .OO

Pergamon

PI1 SO272-7358(96)00016-4

IS BEHAVIORAL INHIBITION RELATED TO THE ANXIETY DISORDERS? Samuel M. Turner and Deborah C. Beidel Department

of Psychiatry and Behavioral Sciences, Medical South Carolina

University

of

Patricia L. Wolff Park Medical

Group,

Terre Haute, Indiana

ABSTRACT. Following a brief summary of extant research on behavioral inhibition (BZ), evio!.+mce far its relationship to the anxiety di.wrdezs i.s examined criticaEy. BZ z’sa behavioral qndtvme that is iokntzjiable at an early age and, at the extreme, appears to be stabkfrom infanq to at least early childhood. AMwugh there is some evidence to suggest that BZ is a characteristic behavioral response style, the avaikbb duta indicate that it is not immutable, but rather is governed to some extent by enviwnmental factors. Additionally, current data suggest lihelihood of a limited relationship between BZ and anxiety disorders, in particular to conditions characterized by m&adaptive social anxiety. However, the exact nature of thti relationship has yet to be elucida&d. Several hypotheses are put forth as to how BZ might be related to the anxiety disoroks.

BEHAVIORAL shyness, objects,

INHIBITION

withdrawal,

and events (Garcia-Coll,

Caucasian research

children

display

has examined

Broberg,

Matheny,

Recently,

explored

1989).

(e.g., Biederman

1992).

BI as defined

Although by Ragan

this

is an early appearing uneasiness,

Ragan,

Lamb, the

fear

1984).

pattern

and physiological

8c Hwang, relationship

is an extensive

and his colleagues

literature

1989),

correlates

1990; Ragan, of BI

characterized situations,

Approximately

(Ragan,

Reznick,

to anxiety

et al., 1990, 1993; Hirshfeld

there

syndrome

of unfamiliar

& Reznick,

behavior

its behavioral

1990,1991,1993;

1991,

(BI)

avoidance,

and

lo-20%

(e.g., Asendorpf, & Snidman,

disorders

on inhibition,

of

substantial

has

et al., 1992; Rosenbaum

has received

by

people,

1987; been et al,,

the construct

the most attention,

of

and it is

Correspondence should be addressed to Samuel M. Turner, PhD, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 615 Wesley Drive, Suite 200, Charleston, SC 29407. I57

158

S. M. Turno; D. C. Be&l, and l? L. Wolff

the behavior syndrome defined by this construct that has been studied most closely in relation to the anxiety disorders. After a brief summary of basic research on BI (in humans and a similar syndrome in nonhuman primates), studies examining the possibility of a link between BI and anxiety disorders will be reviewed. Because the majority of the research on the relationship of BI to anxiety disorders has been conducted using Kagan’s conceptualization of behavioral inhibition, the review of BI will focus heavily on the work of the Harvard group. DEFINITION

OF THE BEHAVIORAL INHIBITION

CONSTRUCT

In the early 198Os, a seminal study introduced the body of research that currently defines the BI construct (Garcia-Co11 et al., 1984). Initially, 21-monthold toddlers were assessed using behavioral, physiological, and parental report measures. The behaviors were assessed under several “challenge” conditions (i.e., unfamiliar or novel situations) and included the following: crying, fretting, distressful vocalizations or facial expressions, withdrawal, and absence of initiation or interaction with the experimenter. Specific inhibited behaviors varied with the particular task, but based on their overall presence or absence, 28% were consistently inhibited, 32% consistently uninhibited, and 40% neither. An aggregate behavioral inhibition index (quantitative score) was constructed using the BI variables plus several others: length of time to initiate interaction (with objects or the experimenter), inhibition of play, and a distressful display in response to the experimenter or an object. This aggregate index was used to determine the stability of BI across time (see stability section below). A number of psychophysiological variables has been examined as potential correlates, but heart rate and heart rate variability have been most often studied and consistently associated with BI (at 21 months of age). Inhibited boys, but not girls, had higher and more stable heart rates and less heart rate variability (Garcia-Co11 et al., 1984). When reassessed 1 month later, inhibited toddlers (regardless of gender) had higher and more stable heart rates during the experimental tasks than the uninhibited children, but the difference was apparent only for those children whose BI index at l-month follow-up placed them in the uppermost or lowest quartile (i.e., extremes of the distribution). At later ages (4 and 5.5)) inhibited children exhibited higher and more stable heart rates during a variety of cognitive and other laboratory “challenges.” However, at 7.5 years of age, differences between inhibited and uninhibited children on cardiac variables were no longer significant statistically. Other physiological variables studied include pupilarly dilation, cortisol, and norepinephrine. At age 5.5, children with BI had larger pupillary dilation during pretrial and trial periods (Reznick et al., 1986) and higher salivary cortisol levels irrespective of the home or laboratory environment (Reznick et al., 1986). Also, home cortisol values correlated significantly with the behavioral index of BI (Kagan et al., 1987). Finally, modest but statistically significant correlations between an index of norepinephrine activity and an aggregate index of BI have been reported (Kagan et al., 1987). CROSS CULTURAL STUDIES Inhibited behaviors similar to BI have been reported by other investigators and provide some corroboration of findings from the Harvard group. Broberg (1993) and Broberg et al. (1990) assessed 144 first-born Swedish children at 16 months and followed them for the next 24 months. Unlike behavioral observations used by the Harvard group, ratings by parents and an independent observer were used to create an initial index of BI. Children who were inhibited at 16 months were more likely to

Behavioral Inhibition and Anxiety

159

be inhibited at 28 and 40 months of age. Inhibition was correlated strongly with mothers’ descriptors of behaviors reflecting restricted sociability and risk avoidance (Broberg, 1993, p. 167). Asendorpf (1990, 1993) used a behavioral assessment paradigm, similar to that used by Garcia-Co11 et al. (1984), for a 4-year study which began when the children (unselected for degree of inhibition) were 3 years, 9 months old. Moderate to high and significant correlations were found between 4 and 8 years of age for inhibition scores based on interactions with unfamiliar people (peers and adults) in unfamiliar environments ( TS= .49 to .75). For unfamiliar peers in a familiar environment, correlation for a parental inhibition index with behavioral measures were low to moderate, but significant (n = .25 to .55). However, for a familiar peer in a familiar environment, none of the correlations was significant (1s = .OOto .20). These results suggest that person familiarity is a critical feature in the attenuation of BI but physical environment familiarity is not. Taken together, these studies provide cross laboratory and cross cultural confirmation of BI. Collectively, the weight of these findings indicate that a response style characterized largely by inhibition appears to be evident in a small proportion of Caucasian children. Furthermore, the evidence suggests that the syndrome is subject to mitigation by certain environmental/psychological factors (see environmental section). STABILITY OF BI Stability of BI can be examined along two dimensions: stability of the behaviors that initially defined BI and stability of the physiological correlates. Below, these two components will be examined separately. Behavioral

Stability

The Harvard cohort has been followed over both short- and long-term follow-up intervals. One month stability data for the behavioral index were significant (r = .63). Ten months stability data, collected in the home (home index) and the laboratory (lab index) both correlated significantly with the original 21-month BI index (r= .39 and r= .66, respectively; Garcia-Co11 et al., 1984). Additional cohort assessments occurred at ages 4, 5.5, 6, and 7.5 years (Rag-an, 1989; Kagan, Reznick, Clarke, Snidman, SC Garcia-Coll, 1984; Kagan, Reznick, & Snidman, 1988; Kagan, Reznick, Snidman, Gibbons &Johnson, 1988; Reznick et al., 1986). At age 4, most children meeting criteria for BI at 21 months continued to exhibit BI (see Kagan et al., 1984 for details). However, some children changed classification. Although 13/22 children initially classified as BI remained so at age 4, nine were less inhibited (but not enough to be classified as uninhibited). Thus, of the original sample of inhibited children, 59% remained inhibited at follow-up. Only one of the originally uninhibited sample was more inhibited at the follow-up. Furthermore, heart rate variability appeared to be a factor in those who became less inhibited. Five of the nine BI children who were less inhibited at follow-up had variable heart rates at 21 months of age. In contrast, 11 of the 13 toddlers who retained their inhibited classification had more stable heart rates at 21 months. Taken together, these findings suggest that even among the extreme group, BI is not an irreversible attribute and that a high and stable heart rate may be a predictor of relatively persistent BI. As a group, those who were labeled BI at 21 months continued to exhibit inhibited behaviors, including caution and restraint during “challenge” and “risk” tasks at age 5.5 (Reznick et al., 1986). Mothers rated these BI children as “shy,” and behaviors

160

S. M. Turner, D. C. Beidel, and I? L. WolJ

commonly both

associated

behavioral

affected.

with anxiety

and

physiological

For example,

mothers

ble heart rate reported lessness

during

and bugs were common cated moderate

extreme

among

(age 21 months 1989).

these same children.

to 7.5 years; Kagan,

Finally, there

of children

other children;

children

who had most

from

the

original

and frequent

behavior

engaged

a relationship

behavioral

Reznick,

Asendorpf

index)

Snidman,

validation sample

1991).

in significantly

that strengthened

likely

with a high and stasleepheights,

At 7.5 years, reassessment

also is cross-cultural

at 4, 6, and 8 years of age (Asendorpf,

played inhibited

the ones

irritability,

stability of BI (based on the aggregate

1988; Kagan, reassessed

constipation,

Children

of BI were

first year. At age 5.5, fears of the dark, elevators,

year interval subset

characteristics

of 10 of the 13 inhibited

chronic

the child’s

also were observed/reported.

indi-

across a 5.5

Gibbons

et al.,

for stability of BI. A

(Asendorpf,

German

1990)

children

less social-interactional

was

who display with

from age 4 to age 8.

Physiological Stability Garcia-Co11

et al. (1984)

heart rate variability nificantly

reported

no consistent

at 21 months

predicted

relationship

and 31 months.

between

heart

However, BI measured

larger pupil size during baseline

laboratory

rate or

at age 4 sig-

recordings

at age 5.5,

whereas the BI index at 21 months did not (Reznick et al., 1986). Norepinephrine level at age 5.5 did not significantly relate to the BI index at 21 months, but was correlated

moderately

Cortisol

with BI at ages 4 (r = .34) and 5.5 (r = .31; Kagan

levels at 5.5 years correlated

21 months

moderately

and significantly

et al., 1987).

with the BI index at

(n = .45) and 5.5 years of age (r = .37; Kagan et al., 1987),

years (coefficient

not reported;

Ragan,

ogy index at age 5.5 consisting rine, and cortisol

Reznick,

& Snidman,

1988).

of heart rate, pupil size, muscle

measurements

correlated

significantly

but not at 7.5

Finally, a physiol-

tension,

norepineph-

with the BI index at 7.5 years.

PRECURSORS TO BEHAVIORAL INHIBITION For the main Harvard sequent

events have been & Gibbons, behavioral response

had higher

younger

in unselected

who were reassessed

responses stability

BI initially was established

assessed

assessed

1989),

top and bottom ed. Heart

cohort,

investigations

lo%,

when selected

a similar

pattern

in conjunction

cohort

Kagan & Snidman,

14 months

subsamples

those who were extremely

suggest that BI may be a stable response The youngest

reactions

inhibited

1991b),

to unfamiliar

for the total sample,

but

on the

at ages 14 and 20 months

than those who were extremely

(see Kagan

Reznick,

of age. Consistent

were used. Based

uninhibit-

et al., 1989 for details).

style, but only at the most extreme

Findings level, and

with high and stable heart rate.

assessed to date consists of 4-month-old

1991a,

However, sub

of age (Kagan,

at 20, 32, and 48 months

of BI at age 48 months

rate showed

only when it occurs

children

at 21 months.

Initial

from year 1 to year 4 were not detected

was enhanced

indices

children.

classified

as high motor-high

infants

(Ragan,

1989;

cry, high motor-low

cry, low motor-high cry, or low motor-low cry, based on behavioral responses to unfamiliar events (see Kagan, 1989, for details). At 9 months, high motor-high cry infants had the highest

fear scores

by high motor-low

when confronted

with novel events followed

cry, and then the two low motor

groups.

At 14 months,

successively all of the

high motor-high cry infants showed at least moderate fear, whereas 14/35 of the low motor-low cry infants showed low to no fear. At 21 months, the high motor-high cry group was more fearful in unfamiliar and novel situations than the other groups (Kagan & Snidman, 1991a; Ragan, Snidman, & Arcus, 1992). These results suggest

Behavioral Znhibitim and Anxiety

161

that reactivity at 4 months (motor activity and emotionality) and fearfulness to unfamiliar stimuli at 14 months predicted an inhibited withdrawn style (i.e., more fearful) to unfamiliar stimuli in the second year of life. Recently, Kagan et al. (1994) reported a cross-cultural comparison of infant reactivity using samples of 4monthold children from Boston, Dublin, and Beijing. The highest arousal levels were recorded by the American infants, followed by the Irish, and finally, the Chinese. Specifically, the American infants were more motorically active and fretful than the Irish infants, who were more active and fretful than the Chinese. Similar differences were found for crying and vocalizations. These results suggest that there are cultural differences in early expression of reactivity. However, whether these early differences are maintained at later ages, or whether initial reactivity predicts the later development of BI in Irish or Asian children has yet to be determined. ENVIRONMENTAL

EXACERBATING OR ATTENUATING

FACTORS

As noted previously, inhibited behavioral styles in children appear to be affected by psychological/environmental characteristics. For example, Kagan, Reznick, Snidman, Gibbons et al. (1988) speculated that parental pressure and encouragement to socialize may influence change to more sociable uninhibited behavior in BI children, but this has yet to be evaluated empirically. Although BI has been conceptualized as a temperamental variable (e.g., Kagan et al., 1984), current evidence suggests that there is cross-situational variability. For example, in the initial study of BI (Garcia-Co11 et al., 1984), behavioral data were collected in the home and laboratory. Although both home and laboratory indexes correlated significantly with the original 21-month BI index (r= .39 and r= .66, respectively), the correlation between the lab and home BI indexes was not significant (7 = .34). Furthermore, the much lower correlation (7 = .39) between home BI and the 21month BI index (which was based on laboratory data) indicates that situational factors influence the manifestation of BI. Broberg (1993) examined the influence of day care experiences (out-of-home, center-based care facility; another family’s home; or own home) on expression of inhibition. Despite the particular environment, all inhibited children engaged in significantly less interactional play when at home. Similar, though somewhat weaker, results were obtained for peer play assessed in an out-of-home care setting. However, inhib ited children cared for in out-of-home settings were somewhat less inhibited than inhibited children raised at home. Asendorpf (1991) found a significant and positive correlation between failed social interactions and BI. As failure experiences increased, so did BI. This suggests that inhibited response styles might be aggravated or perhaps even develop subsequent to certain types of social experiences (in this case failure experiences). These data suggest that several situational/environmental/psychological variables influence the manifestation of inhibited response styles in young children. This, however, does not mean that BI is not a temperamental variable. Rather, it means that BI is a complex behavioral style subject to multiple influences. INHIBITED

BEHAVIOR STYLES IN NON-HUMAN

PRIMATES

Parallel research with nonhuman primates has delineated a behavior pattern strikingly similar to that of children with BI, including “chronic anxiety,” environmental wariness, and timidity with unfamiliar peers and situations (Suomi, 1983). In addition, heart rate reactivity to early-occurring (1 month of age) conditioning trials was

162

S. M. Turnq D. C. Be&l, and F! L. Wolff

correlated with later (12-30 months of age) expressions of anxious behaviors (selfrocking, grasping, and passivity) across different unfamiliar settings (Suomi, Kraemer, Baysinger, & Delizio, 1981). Cortisol levels in newborn monkeys separated from their mothers at birth also have been positively related to cortisol levels and heart rate reactivity (at 18 months of age) in unfamiliar peer interactions. In addition, high cortisol values and heart rate changes were related to more fearful and withdrawn behaviors (Suomi, 1983). Finally, when introduced into an unfamiliar group, monkeys with increased cortisol levels exhibited pacing or withdrawal behaviors (Suomi et al., 1981). Thus, there appears to be a subgroup of infant monkeys who demonstrates behaviors that are: (a) similar to children with BI, (b) stable over time, and (c) exhibited behaviorally and physiologically under challenge conditions. GENETICSAND BEHAVIORALINHIBITION Consistent with the view of BI as an aspect of temperament, researchers have explored a possible genetic basis. At 18 and 30 months of age, MZ twin pairs showed significantly greater concordance for BI (operationalized as fearfulness, emotional tone, and approach/withdrawal behaviors) than DZ twin pairs (Matheny, 1989). Although some measures failed to differentiate groups at some ages, overall MZ correlations were consistently and statistically significantly higher than DZ correlations. DiLalla, Kagan, and Reznick (1994) reported that, overall, identical twins were more likely to be rated as extremely inhibited than were fraternal twins. Also, concordance rates and heritability estimates indicated that MZ pairs were more similar in their inhibited behaviors than were DZ twins. In addition, the heritability estimate for the extremely inhibited children was higher than for the entire group, suggesting that genetic influences may be particularly important for this extreme group. Such a finding is consistent with most of the BI literature where the characteristic behavioral responses are most stable in the most extreme group. Finally, Robinson et al. (1992) reported that estimates of genetic correlation across three ages (14, 20, and 24 months) were .81, greater than 1.0, and .65, respectively. Although there are a number of limitations to current genetic studies (e.g., the Robinson et al., 1992 study did not use antigen typing and adopted away studies have not been conducted), data suggest that there might be a genetic factor in BI, particularly in those with extreme manifestation of the syndrome. LIMITATIONSOF FINDINGS ON BEHAVIORALINHIBITION Several methodological weaknesses limit interpretation of results from these basic studies of BI. First, attempts to assess consistency across ages were plagued by the task differences across the various assessment protocols. Although use of different tasks was necessary to match developmental stage of the child, there was no attempt to establish task equivalency. Thus, tasks at one age may have been more capable of differentiating the groups, possibly explaining the different findings at different ages. Second, because physiological dimensions sometimes have been examined in terms of their ability to differentiate between groups, while at other times correlational procedures were used to indicate the strength of the relationship, the physiological findings from these studies are somewhat difficult to interpret. Third, physiological variables have been less stable than behavioral variables. This could be because the age range used in these studies represent periods of rapid physical maturation, making it possible that the inconsistent findings may reflect changes in physical development. Fourth, even with associated instability, the strongest physiological variable

Behavioral Inhibition and Anxiety

163

associated with BI is a higher and more stable heart rate. This result seems consistent from early ages (21 months) well into childhood (7.5 years). Although there is some support to suggest that other physiological parameters might be useful, findings to date are rather inconsistent. Fifth, with respect to the Asendorpf (1993) finding that environmental factors act to attenuate inhibition, the study’s conclusions are limited because the children were not randomly assigned to type of day care setting. Thus, parental bias toward a particular setting cannot be ruled out, although no evidence that such bias existed was presented. In summary, the preponderance of the data support usefulness of the BI construct. Furthermore, the fact that a similar behavioral pattern has been observed across lab oratories, cross-nationally, and cross-species provide additional support. However, closer examination of the findings from the Harvard group suggests that BI is not as robust or uniform as heretofore believed. Some children (approximately 40%)) identified as behaviorally inhibited at 21 months, became less inhibited with increased maturation (as early as age 4). Because inhibited children can become less inhibited given certain environmental circumstances, it appears that specific behaviors defining the construct are not immutable even if they have a biological basis, although the tendency to react in an inhibited fashion, given specific environmental conditions might be. Finally, reconceptualizing BI as a dimensional construct rather than a qualitatively different behavior would be consistent with the findings that BI is stable but only in a very small group and only in those who exhibit both the behavioral and physiological features. BEHAVIORAL

INHIBITION

AND THE ANXIETY

DISORDERS

In recent years, there has been considerable interest in the etiology of anxiety disorders. Although it seems clear that anxiety states are familial, the nature of this familial factor remains unclear. Furthermore, there has been considerable speculation about the relationship of childhood problems and adult anxiety disorders. Only a relatively small number of studies has addressed this question, except for separation anxiety, and most are retrospective in nature. Because BI includes many behaviors typically associated with anxiety syndromes (e.g., withdrawal, increased latency to speak, avoidance of novel situations, difficulty initiating conversations, reluctance to enter strange or unfamiliar settings, heightened physiological reactivity), questions about a possible relationship have been posed. In a seminal study, Rosenbaum et al. (1988) assessed 56 Caucasian children aged 2-7 years old who were matched on age, gender, and birth order. The children were the offspring of parents with Panic Disorder (PD) with or without Agoraphobia (AG); comorbid PD and Major Depressive Disorder (PD plus MDD); Major Depressive Disorder (MDD); or no PD, AG, or MDD (Control). The last group consisted of sib lings of patients with ADD or children of parents treated for other disorders such as tobacco dependence, Generalized Anxiety Disorder, or obesity. The children participated in the BI assessment protocol at the Harvard laboratory (GarciaColl et al., 1984; Ragan et al., 1987). Behaviors measured included latency to first, second, and third spontaneous comment, frequency of spontaneous comments, frequency of small and gross body movements, and smiles. Children of PD parents, either alone or with comorbid MDD, had longer latencies to speak to an examiner and made significantly fewer spontaneous comments than children of the control group. Children of parents with only MDD did not differ from the other groups. Similar findings were obtained for rates of BI within each group, such that children of PD parents, with or

164

S. M. Turnet; D. C. B&X, and I? L. Wolff

without MDD, were significantly more inhibited than children of parents from the control group. Again, children of MDD parents did not differ from the other groups. For all children, rates of BI were: PD only, 85%; PD and MDD, 70%; MDD only, 50%; and control, 15%. These results suggested that presence of panic (PD only and PD plus MDD) in parents was associated with a greater likelihood of BI in the offspring. However, 50% of the children of parents with MDD alone manifested BI. Thus, although it was clear that children of the ill parents were more likely to manifest BI than controls, the high rate of BI in offspring of depressed parents mitigate against attributing the presence of BI solely to panic. This study has several methodological limitations which affect the interpretation of the data. First, the composition of the control group was mixed. The majority of those in this group consisted of siblings of children with ADD plus the offspring of a few adults being treated at Massachusetts General Hospital (MGH) . Although none of the parents or spouses in the group had PD or MDD, absence of other diagnostic conditions is not stated clearly. This is a significant limitation for a study whose purpose was to determine the presence of BI in offspring of parental groups. A second limitation is the substantial deviation in the way children were labeled as inhibited. In the original GarciaGo et al. (1984) study (i.e., Kagan sample), the label “inhibited” was assigned to children who exhibited nine or more (separate) behaviors across six different tasks. “Uninhibited” was used to describe children who exhibited two or fewer behaviors across the same tasks. “Neither” was used to describe those children who exhibited between three and eight behaviors. Out of the original 118 children in the Kagan sample, 40% were classified as “neither” and, thus, were removed. In contrast, the Rosenbaum et al. (1988) study classified children into two mutually exclusive categories: inhibited and not inhibited. In addition, classification was based on two variables (long latency to spontaneous speech with the examiner and total frequency of spontaneous comments) rather than the broader range of behaviors used in the Kagan sample. Long latency and few comments indicated inhibited status, whereas short latency and many comments denoted uninhibited status. Thirty percent of the Rosenbaum et al. (1988) sample displayed inconsistent behavior even on these two variables (i.e., they had short latency but few comments or long latency but many comments). According to the original protocol (Garcia-Co11 et al., 1984), these children should have been eliminated from the sample. However, because number of spontaneous comments was considered “more sensitive” than latency (Ragan et al., 1987), these children were classified based on this single variable. In summary, then, behaviors used to classify this sample were not consistent with the prior classification system used by Kagan and colleagues, and the deviation in procedure questions the equivalency of the samples and the interpretation of the results. In short, there is sufficient deviation in the Rosenbaum et al. (1988) study such that it cannot be considered a direct test of the relationship between BI (as defined by Ragan and colleagues) and anxiety disorders in the parents of these children. Biederman et al. (1990) examined three samples of children. The first group consisted of 30children from the Rosenbaum et al. (1988) sample who were deemed to be at risk because of a parental diagnosis of panic (MGH at risk). The second sample (healthy control group) consisted of 20 nonadopted Caucasian children recruited from a pediatric primary care unit. These children were screened and determined not to have a psychiatric or medical diagnosis. The final group of 41 children (22 inhib ited and 19 uninhibited) were part of Kagan’s longitudinal cohort. Mothers were interviewed with the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P) to determine the child’s diagnosis, but children themselves were not inter-

Behavioral Inhibition and Anxiety

viewed.

The

at-risk

sample

was divided

into

inhibited

to each

other

(n = 12) groups

and were compared

Results indicated

that the BI group was significantly

disorders

per child and two or more

dren were significantly healthy

more

(n = 18) and

noninhibited

as well as to healthy

controls.

more likely to have four or more

disorders

per child.

likely to have overanxious

The inhibited

disorder

as compared

chilto the

controls.

For the BI group (more

anxiety

165

DSM-III

in the Kagan

anxiety

and uninhibited

children

der was significantly

longitudinal

and general common

disorders

uninhibited

status. Of those inhibited

a fear of public

were significantly

speaking,

44%

statistically.

in uninhibited

and phobic

more

common

children

disorder

did not differ between

was found inhibited

defiant

than inhibited

disor-

children,

in those with inhibited

with a phobic

had a fear of strangers,

trend between

Oppositional

children

disorder,

33%

called on in class, and 33% had fear of crowds. Unlike overanxious

this same

but the difference

was not significant

more

cohort,

disorders),

reported

a fear of being

the at-risk sample,

the inhibited

than

56% reported presence

and uninhibited

of

groups

in

this sample. Although

results of this study provided

of BI to the anxiety disorders, conclusions

can be drawn.

additional

owing to significant The

inequivalency

information

on the relationship

methodological

limitations,

of the BI sample

in these

noted previously. Also, parents

of the Ragan sample and the healthy control

not participate

interview,

in a diagnostic

Because the familial relationship (e.g., Turner, Beidel, & Costello, risk sample

may have been

hence,

no parental

diagnoses

no firm

studies

was

group did

were available.

of anxiety disorders has been previously established 1987), presence of anxiety disorders in the MGH at

inflated

because

of the parents’

anxiety

rather

than the

presence of BI. A third difficulty is the high rate of ADD found in the inhibited dren, particularly the MGH at risk sample, where the percentage of children ADD was 33%. for several

In the Ragan

reasons.

sample,

and healthy

expectations

of ADD in the MGH at risk sample

for any of the anxiety

rate of ADD for the inhibited (17%)

the rate for ADD was 18%. This is problematic

First, prevalence

than the prevalence

control

children

groups

given the descriptions

this reversal did not occur

disorders.

was higher

(10%).

Second,

(33%)

than for the not inhibited

Both of these findings

of BI and the pathology

in the Kagan sample,

Rosenbaum the offspring. Ragan’s

et al. (1991)

a direct

Presence

inhibited

out any known interviewed

psychiatric

with the NIMH were determined

dren were not interviewed Overall,

parents

or uninhibited or medical Diagnostic

Interview

parental

in the parents

(n = 27) of a randomly

sion of the Diagnostic diagnoses

of disorders

(n = 22)

(n = 35) and siblings

exists between

further

contrary

diagnoses, Interview

to

also were assessed. Schedule

and BI in (72 = 45) of

was assessed.

group of children (DE)

Parents

(n = 20)) withParents

and a modified (DICA).

the

more close-

disorder

(n = 75) and siblings

and Adolescents

based on a structured

questions

to examine

psychiatric

(n = 19) children selected

for Children

appear

of ADD. Furthermore,

where the rate was 18% for the inhib

used family history methodology

relationship

was higher

in the at risk sample,

ited and 32% for the uninhibited groups. This discrepancy equivalency of these samples of inhibited children. ly whether

chilwith

were ver-

The siblings’

interview with the parents

(i.e., chil-

directly).

of inhibited

children

were more likely to have histories

for the of two or more anxiety disorders,

to have a higher percentage

iety disorders,

higher

and to have a significantly

risk for a current

the parents of uninhibited or normal children. Disorders between the groups were social phobia, avoidant disorder,

significant

of childhood

anx-

anxiety disorder

than

accounting for difference and overanxious disorder,

166

S. M. Turn,

D. C. Eieide&and l? L. Wolff

all of which were higher in parents of children with BI than the other two groups. For the siblings, differences in rates of psychopathology among the three groups were not significant. Because this study used the original Ragan sample and the original classification of inhibited and uninhibited, it does not suffer from the limitations of those using the MGH at risk sample. Furthermore, because children in the Kagan sample were not selected based on having a parent with an anxiety disorder, findings provide a less biased assessment of the relationship between BI and anxiety. Results indicated that parents of BI children were significantly more likely to have anxiety disorders of a socialevaluative nature. Rosenbaum et al. (1992) assessed both parental and child diagnoses in the two previously described groups, the at-risk group (n = 31) and the Ragan longitudinal sample (n = 40). Sixty parents from the at-risk group and 75 parents from the Ragan sample were assessed for the presence of psychopathology. Parents were interviewed using the NIMH Diagnostic Interview Schedule (DIS; to assess for current anxiety disorders) and portions of the DICA (to assess for past childhood anxiety diagnoses). Children from these two groups were diagnosed based on DICA-P interviews with their mothers. Children were then divided into three groups: (a) BI plus an anxiety disorder(s), (b) BI only, and (c) no BI-no anxiety disorder. Among the at-risk group, parents of children with BI plus an anxiety disorder were significantly more likely to have a history of an adult anxiety disorder than parents of children with BI only or no BI-no anxiety. For the Ragan longitudinal sample, parents of children with BI plus an anxiety disorder were significantly more likely to have a history of adult or childhood anxiety disorder than parents of children with no BI-no anxiety. However, there was no significant difference between parents of children with BI plus anxiety and BI only for the presence of adult or childhood anxiety disorders. Children with BI plus an anxiety disorder from the at-risk group were more likely to have a parent with a history of anxiety disorder than children with BI plus an anxiety disorder from the Ragan longitudinal sample, but this could be explained by sample recruitment strategies. Finally, as an exploratory analysis, the two samples were pooled and differences between BI only and no BI-no anxiety were examined. Prevalence of social phobia was higher for parents of children with BI only (10%) than for their counterparts (0%). Similar to the Rosenbaum et al. (1991) study, this finding suggests that the possible relationship between BI and anxiety disorders has a social basis, although the prevalence rate in this study (10%) suggests that this relationship may not be very strong. Results of these studies indicate that there is some relationship between BI in children and anxiety syndromes in their parents, especially when BI and anxiety in the children co-occur. The most parsimonious explanation is that anxiety is the critical factor. Children of anxious parents are more likely to have an anxiety disorder than children of normals and other diagnostic groups (e.g., Turner et al., 1987). Likewise, parents of children with a diagnosed anxiety disorder are more likely to suffer from anxiety themselves (e.g., Last, Hersen, I&din, Orvaschel, & Perrin, 1991). Thus, it remains unclear whether BI might be a predisposition to anxiety, the parameter through which the relationship is mediated, or a secondary manifestation of some other primary process (such as anxiety). In another study from this laboratory, Hirshfeld et al. (1992) examined presence of anxiety disorders in the children, parents, and siblings of the Ragan longitudinal sample. All children were 7.5 to 8 years of age when psychopathology was assessed. Parents were interviewed with the NIMH-DIS and portions of the DICA. Psychiatric interviews (DICA-P) were conducted with mothers about their children (no direct

Behavioral Inhibition and Anxiety

167

child interviews). Using the BI index, the children were classified according to one of four categories: Stable-inhibited (n = 12)) unstable-inhibited (n = lo), stable-uninhib ited (n = 9)) and unstable-uninhibited (n = 9). The stable-inhibited children had significantly higher rates of any anxiety disorder, more than two anxiety disorders and phobic disorders as contrasted to the other three groups combined. Parents of stable-inhibited children were significantly more likely to meet criteria for two or more childhood anxiety disorders, avoidant disorder of childhood and continuing disorder (having both a childhood and adult anxiety disorder), than parents of children in the other three groups combined. These findings suggest that children with stable inhibition tended to have more anxiety disorder diagnoses than uninhibited or unstable-inhibited children, and the anxiety disorders diagnosed were largely characterized by maladaptive social anxiety. In the most recent publication, Biederman et al. (1993) reported a S-year followup of children from the MGH at risk sample and the Ragan sample. For this investigation, the samples were pooled to create two groups: inhibited and noninhibited. Children with BI were more likely to have four or more disorders and two or more anxiety disorders. In addition, these children were more likely to have avoidant disorder, separation anxiety disorder, and agoraphobia. Rates for presence of disorders at follow-up were increased over the rates at initial assessment. Among those children without a disorder at baseline, at follow-up BI children were more likely to have (a) two or more anxiety disorders, (b) avoidant disorder, and (c) separation anxiety disorder. Finally, when children with stable BI were compared to all others, they were more likely to have two or more anxiety disorders and avoidant disorder. Because this study used the same MGH at risk group as in previous investigations, the same sample limitations apply. Furthermore, at risk BI children had prevalence rates of 50% for oppositional disorder and 50% for ADD for those who did not have a disorder at baseline. Implications of these high rates of externalizing disorders were not discussed. However, high rates in this group compared to the much lower rates in Kagan’s sample (7% for ADD and 11% for oppositional disorder) again highlight the samples’ disparities. In summarizing the data from this series of studies, several conclusions can be made. The findings from any one study in this series are not particularly strong because each suffers from a number of significant methodological weaknesses. In addition, data interpretation problems that cut across studies must be noted. Most noticeably is the complication of the interpretation created by combining disorders and characterizing the outcome in terms of number ofdisorders. This grouping rep resents an attempt to control for severity of psychopathology in these children inas much as it was felt that all children affirmatively endorse a large number of symptoms (J. Rosenbaum, personal communication, December 28, 1994). Thus, the grouping of disorders into larger clusters was an attempt to impose more stringent criteria on the determination of “true” psychopathology, providing a stricter determination of Ucaseness.n However, by grouping the data in this fashion, a clear relationship between parental and child diagnosis cannot be determined. Furthermore, this type of grouping limits the opportunity to determine if BI is associated with a particular anxiety disorder. A second limitation of this series of studies is that not all parents were assessed thoroughly for presence of psychopathology, yet they were considered to be normal or healthy controls. Without complete information about the parent’s psychiatric condition, it is difficult to meaningfully interpret the findings. At other times, a priori selection criteria confounded the intent for which the groups were to be used. For

S. M. Turnq

168

example,

children

because

of parents

of their parents’

interviewed

to determine

ly to have an anxiety because

with panic

diagnosis.

disorder.

disorder

of behaviorally

However,

diagnosis,

were not surprising.

in the

inhibited

group

the nature

of these disorders

Furthermore,

study, these

inhibited

children

of an anxiety

What can be concluded,

have

as at risk for BI parents

were then

were more like-

given that the sample was originally

the findings

of BI children stable

were targeted

In a subsequent

if parents

of the parents’

D. C. Beidel, and l? L. Wolff

more

anxiety

selected

disorder

in the parents

however,

is that children

disorders

as do their

parents.

are socialevaluative.

CONCLUSIONS To date, research

on BI suggests

that the behavioral

pattern

appears

ble over the years of young

childhood

for those who manifest

who show high

heart

In essence,

expected jects

and stable

in about

10% of the assessed

were recruited,

where

this figure

the percentage

siderable

degree

of similarity

across

variable,

the response

tability. As the infant behaviors. unfamiliar

sample.

cannot

Because

BI pattern

species

BI has been considered

a temperamental basis

population

observed

by high motor

by withdrawn,

with a conThis suggests

variable. Although

influences.

activity and irri-

passive, and avoidant

are more fearful

(Rotherbart

and

can be

in which sub

to the general

to a host of environmental

BI is manifested

imply a constitutional

pattern

of the manner

has been

style is characterized

matures,

the stable

as well as cross culturally.

likely subject

Some children exhibiting this pattern persons, situations, and novelty.

perament

then,

be extrapolated

likely is lower. The

that BI is a dimensional In early infancy,

rate.

early and is sta-

it in its extreme

and tend to avoid

some theories

& Derryberry,

1981;

of tem-

Thomas

8c

Chess, 1977), the importance of temperament as an interaction between a child and the environment also is acknowledged (Garrison & Earls, 1987). Some empirical evidence supports presence of a constitutional factor for some aspects of temperament. For example, genetic studies suggest high heritability estimates for social introversionextroversion, stitutional

but lesser support

variable,

for fearfulness

toward social introversion, behaviors marily under challenge “conditions.” ject to the influence 1993; Broberg (1990,

environment existence Current ferent

increases.

with Caucasians.

methodological

weaknesses,

by which behavioral

is a trend

suggested

racial,

1993: Broberg,

ethnic,

s studies

that the expression

and that inhibition

decreases

or cultural

for children

of BI to anxiety

the most important

inhibition

was defined.

were identified

of

as physical

BI per se have

differences

in the

(Garcia-Co11

suffer from a number of which involves dif-

When

the focus is limited

using the procedures

et al., 1984),

the outcome

with BI to have four or more

more anxiety disorders when compared to uninhibited the presence of more disorders is indicative of caseness, dren with BI are more with BI are significantly

1990, 1991,

et al., 1986). Asendorpf

population,

the relationship

by Kagan and colleagues

First, there

(Asendorpf,

pri-

of BI appears sub-

Finally, to date all studies assessing Thus,

to only those studies where children defined

propensity

of BI is unclear.

studies examining

criteria

factors

largely by unfamiliarity

or manifestation

of significant

However, even the expression

with a school-age

familiarity

conducted

Thus, if BI is a con-

a behavioral

that are seen in infancy and early childhood

of environmental

1993), conducted

1983).

considered

et al., 1990; Kagan et al., 1984; Reznick

BI was determined been

(Goldsmith,

it might be more appropriately

originally is as follows.

disorders

children. In other these data indicate

or two or words, if that chil-

likely to have a significant anxiety syndrome. Also, children more likely to have phobias (fear of public speaking, fear of

Behavioral Znhibitim and Anxiety

169

strangers, fear of crowds, and fear of being called on in class) than uninhibited children (Biederman et al., 1990). Furthermore, the group differences apparently are accounted for by children who retain their classification of inhibition (stably inhibited) across repeated assessment intervals (Hirshfeld et al., 1992); and the specific fears have a social (crowds or strangers) or social-evaluative (public speaking, being called on in class) basis. Second, with respect to the parents of these children, one study (Rosenbaum et al., 1991) reported that parents of children with BI were more likely to meet criteria for two or more anxiety disorders, a past history of a childhood anxiety disorder, and a current anxiety disorder. Differences between groups were accounted for by differences in rates of social phobia, avoidant disorders of childhood, or overanxious disorder, all of which were higher in the parents of BI children. Thus, it would appear that the data indicate that BI is more closely associated with disorders characterized by social-evaluative anxiety. However, even this finding must be tempered because a second study with the same cohort (Rosenbaum et al., 1992) revealed that it was the parents of children with BI plus an anxiety disorder who were more likely to have a history of child or adult anxiety disorders. When children with BI only were compared to children with no BI-no anxiety disorder, no group differences emerged. Thus, the critical factor seems to be a familial pattern of anxiety rather than BI per se. This would suggest that it is the familial history of anxiety that is the key rather than presence of BI. Finally, although current evidence for a relationship between BI and anxiety disorders is rather meager, children in the sample have not passed through the age of risk. Thus, continued follow-up studies ultimately will determine if early-appearing BI predicts the onset of anxiety disorders. Specific hypotheses as to exactly how BI might lead to development of anxiety disorders have yet to be developed and examined. One hypothesis is that BI is a genetically transmitted trait that culminates in development of maladaptive anxiety states. In this scenario, BI is the early syndromal features of the genetically transmitted disorder. Available data provide little support for this hypothesis. Furthermore, genetic variables are thought to exert their influence by predisposing the individual to interact with the environment in a certain fashion, in this case, with a withdrawn and tentative interactional style (e.g., Starr, 1967). Thus, in order for a disorder to develop, the appropriate “anxiogenic environment” is needed. For example, because children with BI do not readily engage in social contact, they may not learn appropriate social skills. In turn, such ineptitude may cause them to be neglected or rejected by their peers, further increasing isolation. When a situation requiring social interaction cannot be avoided, the individual is ill equipped to deal with it and may experience increased physiological arousal and subjective distress, which increases the likelihood of social failure and leads to further avoidance and apprehension. Asendorpf (1993) provided support for such a process, noting a significant and positive correlation between failed social interactions and BI. Thus, in this example, BI is the basis for the development of anxiety disorders by fostering a behavioral style that is not conducive to adaptive social functioning but the full emergence of a disorder is dependent on environmental factors. Such a view could accommodate the data illustrating that BI is environment responsive and that not all children with BI have anxiety disorders. On the other hand, this conceptualization cannot explain why children who are uninhibited have anxiety disorders (e.g., Biederman et al., 1990). A second hypothesis is based on the notion that BI is a genetically transmitted predisposition, that individuals with BI are more prone to respond intensely to anxiety producing events, and through this mechanism are more vulnerable to develop maladaptive

170

S. M. Turner;D. C. Beidel, and tl L. Wolff

anxiety. Garrison perament,

and Earls (1987)

and early behavior

suggest that the role of such a predisposition,

tem-

patterns dimensions 6y themselvesproba-

may be a mediational one. That is, early temperamental

bly contribute a minimal amount to explanations of psychopathology during childhood or adulthood. Their real utility may reside in demonstrations interactions

with a host of environmental

der, age, social cks

and the larger cultural

This type of conceptualization

context.

Another

hypothesis

assumes

ulatory systems are different more vulnerable

to the development

iety (Gray, 1970, behavioral

1982)

inhibition

postulates system

the limited

stability

with BI develop

anxiety

that physiological

in individuals

temperament

activation

of the BI condisorders.

systems or behavioral

with BI, and that affected

that there

are two brain

and the behavioral

motivational

activation

reg-

individuals

of anxiety as a result. One existing

(BIS)

by gen-

(p. 65)

would explain

struct as well as why only a subset of children

of critical

which are, in turn moderated

factors,

are

theory of anxsystems: the

system (BAS).

The

BAS regulates behavior in the presence of rewards whereas the BIS regulates behavior in the presence of punishment. According to Gray, individuals differ in the relative strengths of these systems. For example, more susceptible to warnings of punishment, conditioned

fear responses

more

readily. Thus,

Gray (1970) noted that introverts are react with fear responses, and develop introverts

(i.e., behaviorally

inhibited

children) would be more likely to develop maladaptive anxiety. Yet another hypothesis is that BI is only one manifestation

of a more

complex

behavioral

are similar

to those

defined

system. The

behaviors

by the constructs

comprising

of trait anxiety

neuroticism (Eysenck & Eysenck, 1984), and clearly resemble those

BI, for example,

(Spielberger,

Gorsuch,

& Lushene,

1985), and negative affect (e.g., typically described as introverted.

1970),

Watson 8c Clark, BI might be the

behavioral manifestation of one or more of these more pervasive behavioral patterns. All of these constructs probably refer to similar behavior and might actually be varying explanations a manifestation

of the same or similar phenomena. of a larger and more comprehensive

sition, with its importance pervasive response pattern. BI uniformly appear

predisposes

to completely

viable. This, of course, hypotheses

In this case, BI might merely be personality

or behavioral

dispo

for the development of anxiety dependent on this more Given that extant data do not support the contention that one to anxiety,

explain

and the fact that other

the data, this latter

is purely speculative

interpretation

hypotheses might

do not

be the most

at this point but one can generate

testable

based on this perspective.

The hypotheses

discussed

thus far are not mutually

bined to form a more comprehensive

hypothesis

exclusive

regarding

and could

be com-

the role of BI in the devel-

opment of anxiety disorders. However, even a hypothesis using this combination of constitutional and environmental factors is insufficient because it is based on the presumption that BI is necessary, but not sufficient, for the development of anxiety disorders.

However,

BI clearly

with anxiety disorders et al., 1990).

is not present

(uninhibited

children

in all individuals

(i.e.,

it is not necessary)

develop anxiety disorders;

e.g., Biederman

In summary, then, the most parsimonious explanation for the relationship of BI to the anxiety disorders, given the current status of the research, is that BI might represent one, but not the only, factor associated with the development of anxiety disorders. disorders,

That is, BI is not necessary or sufficient for the development of anxiety although the presence of BI may make an individual more vulnerable to

Behavioral

Inhibition and Anxiety

171

the development of these disorders. This explanation accounts for the vulnerability factors described above (e.g., negative affectivity, Gray’s theory of the disordered behavioral inhibition system), yet because alternative etiological pathways are acknowledged, it is broad enough to allow for the disorder to be acquired through other mechanisms. Such a hypothesis is consistent with the research findings that anxiety disorders are acquired through different mechanisms (Ost & Hugdahl, 1983; Rachman, 197’7) rather than having a singular etiology, and with the current data indicating that children without BI nonetheless present with anxiety disorders. Based on all data presented, approximately 10% of the children assessed at 21 months for the presence of BI remained inhibited throughout middle childhood. Thus, a relatively small percentage of those found to have BI remains so over several years. It is these children, then, that are likely to constitute the group at highest risk for development of anxiety disorders.

Acknowledgemmts

-

Preparation of this manuscript was supported in part by NIMH grant MH

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