J Abnorm Child Psychol (2006) 34:799812
DOI 10.1007/s10802-006-9079-y
ORIGINAL ARTICLE
The Interactive Role of Anxiety Sensitivity and Pubertal Status
in Predicting Anxious Responding to Bodily Sensations among
Adolescents
Ellen W. Leen-Feldner Laura E. Reardon
Laura G. McKee Matthew T. Feldner
Kimberly A. Babson Michael J. J. Zvolensky
Published online: 18 November 2006

C Springer Science+Business Media, LLC 2006
Abstract The present study examined the interaction be-
tween pubertal status and anxiety sensitivity (AS) in predict-
ing anxious and fearful responding to a three-minute vol-
untary hyperventilation challenge among 124 (57 females)
adolescents between the ages of 12 and 17 years (Mage =
15.04; SD = 1.49). As predicted, after controlling for base-
line anxiety, age, and gender, there was a significant inter-
action between pubertal status and AS in predicting anx-
ious responding to bodily sensations to the hyperventilation
challenge. Specifically, adolescents reporting more advanced
pubertal status and higher levels of AS reported the great-
est post-challenge self-reported anxiety focused on bodily
sensations, whereas pubertal status had relatively less of an
effect on low AS adolescents. A test of specificity also was
conducted; as expected, the interaction between AS and pu-
bertal status was unrelated to generalized negative affectivity,
suggesting the predictor variables interact to confer specific
risk for anxious responding to bodily sensations. Finally, ex-
ploratory analyses of psychophysiological reactivity to the
challenge indicated AS, but not pubertal status, moderated
the relation between challenge-related change in heart-rate
and post-challenge anxiety such that high AS youth who
had experienced a relatively greater heart-rate change re-
ported the most anxious reactivity to the challenge. Results
are discussed in relation to theory regarding vulnerability to
anxious responding to bodily sensations among adolescents.
E. W. Leen-Feldner (
) L. E. Reardon M. T. Feldner K. A.
Babson
University of Arkansas, Department of Psychology,
216 Memorial Hall, Fayetteville, AR, 72701
e-mail: eleenfe@uark.edu
L. G. McKee M. J. Zvolensky
University of Vermont, Department of Psychology,
John Dewey Hall, Burlington, VT 05405
Keywords adolescent . hyperventilation . pubertal status .
anxiety sensitivity . panic vulnerability
Puberty is a key developmental process characterized by pro-
found biopsychosocial changes that occur in a relatively short
period of time (Rogol, Roemmich, & Clark, 2002; Sheehy,
Gasser, Molinari, & Largo, 1999). These hormonallydriven
changes typically co-occur with unexpected and/or undesir-
able bodily events (e.g., Costos, Ackerman, & Paradis, 2002;
Omar, McElderry, & Zakharia, 2003), increased susceptibil-
ity to negative affect (Brooks-Gunn, Graber, & Paikoff, 1994;
Susman, Dorn, & Chrousos, 1991), and enhanced emotional
lability (Buchanan, Eccles, & Becker, 1992; Spear, 2003).
In addition, empirical evidence suggests an association be-
tween pubertal stage and psychopathology, including eat-
ing disorders (Killen et al., 1992), substance use problems
(Patton et al., 2004), and depression (Angold, Costello &
Worthman, 1998; Patton et al., 1996). Overall, available data
indicate puberty may be important for better understanding
affective vulnerability and psychopathology. However, rela-
tively little is known about the association between puberty
and anxiety psychopathology.
Although in its relative infancy, evidence is emerging that
links puberty to panic attacks. In a groundbreaking study,
Hayward and colleagues (1992) administered structured clin-
ical interviews to determine panic attack history to an un-
screened sample (n = 754) of 6th and 7th grade females, who
self-reported pubertal status using the Tanner staging system.
Findings from this cross-sectional analysis indicated a two-
fold increase in the likelihood of having had a panic attack for
each one-point change in Tanner stage. In a follow-up study,
Hayward and colleagues (1997) examined pubertal timing in
relation to panic attack status among 758 adolescent females
across a six-year period. Compared to their on-time coun-
terparts, early maturing girls were significantly more likely
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to have experienced a panic attack. In addition, an interac-
tion was observed such that, relative to the rest of the sam-
ple, early maturing females with a history of internalizing
symptoms had the highest overall risk of developing a clin-
ical disorder (including panic disorder). These data suggest
that puberty is related to panic attacks and that individual dif-
ference factors may interact with pubertal status to increase
panic-relevant vulnerability.
Although promising, the extant work on puberty and panic
vulnerability currently is limited in at least two regards. First,
existing work has thus far focused on psychologically un-
screened adolescents (i.e., youth with psychopathology have
not been excluded). As a result, it is not clear whether pre-
existing psychopathology played a role in the documented
puberty-panic association. For example, given the link be-
tween puberty and other mental health problems (e.g., Patton
et al., 2004), it may be that psychopathology (e.g., substance
abuse/dependence, clinical levels of depression), rather than
pubertal status per se, may at least partially explain the
puberty-panic linkage. To address this methodological lim-
itation of previous studies, investigations need to focus on
adolescents who have not yet developed psychopathology;
in this way, observed findings can be more confidently at-
tributed to the predictor variables of interest rather than
factors related to psychopathology (Forsyth & Zvolensky,
2002; Zvolensky, Lejeuz, Stuart, & Curtin, 2001). Overall,
this methodological approach is clinically-relevant and the-
oretically useful, as the potential confound associated with
pre-existing psychopathology is delimited, thereby allowing
researchers to interpret findings in terms of risk-factor (eti-
ological) processes. Such data inform our understanding of
vulnerability processes among youth who have not yet devel-
oped panic psychopathology and help to specify for whom
or under what conditions panic problems develop (Mrazek &
Haggerty, 1994).
Second, little is known about the variables that may mod-
erate the association between puberty and panic vulnerabil-
ity. The relative neglect of this empirical question is impor-
tant, particularly since puberty is a normative (Rosenfeld &
Nicodemus, 2003) developmental process. Thus, it is not
likely that changes associated with puberty alone are
pathogenic in their own right, but rather, increase risk for
psychopathology only under certain conditions (e.g., among
psychologically vulnerable adolescents; Buchanan et al.,
1992). This conceptualization is consistent with extant the-
ory and research on affective vulnerability (e.g., accentuation
hypothesis; Caspi & Moffit, 1991; 1993); specific individual
differences may be critical to understanding why puberty is
characterized by heightened vulnerability for psychopathol-
ogy among some adolescents.
In light of these limitations, we sought to examine the
moderating role of anxiety sensitivity on the puberty-panic
association among psychologically healthy adolescents.
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J Abnorm Child Psychol (2006) 34:799812
Anxiety sensitivity (AS) is a well established panic-relevant
individual difference variable reflecting a cognitive vulner-
ability to experience fear in the context of bodily arousal
(Barlow, 2002; McNally, 1990; Reiss & McNally, 1985).
At least four lines of research support the conceptualiza-
tion of AS as a panic-relevant variable risk factor (Kraemer,
Lowe, & Kupfer, 2005; Zvolensky, Schmidt, Bernstein, &
Keogh, 2006). First, AS predicts anxious and fearful re-
sponding to biological challenge procedures among youth,
even when conceptually-relevant variables such as trait anxi-
ety and negative affectivity are accounted for (Leen-Feldner,
Feldner, Bernstein, McCormick, & Zvolensky, 2005; Rabian,
Embry, & McIntyre, 1999; Unnewehr, Schneider, Margraf,
Jenkins, & Florin, 1996). Second, AS is associated with panic
symptomatology, even after controlling for symptoms of
general anxiety and depression (Deacon, Valentiner, Gutier-
rez, & Blacker, 2002), and is elevated among adolescents
with panic attacks (Ginsburg & Drake, 2002; Lau, Calamari,
& Waraczynski, 1996) and panic disorder (Kearney, Albano,
Eisen, Allan, & Barlow, 1997) compared to those without
such histories. Third, work with youth (Ollendick, 1995) and
adults (Telch et al., 1993; Smits, Powers, Cho, & Telch, 2004)
indicates AS is sensitive to change following clinical inter-
vention for panic-related problems. Finally, work completed
with adults (Li & Zinbarg, in press; Maller & Reiss, 1992;
Schmidt, Lerew, & Jackson, 1997; 1999) and adolescents
(Hayward, Killen, Kraemer, & Taylor, 2000) indicates AS
prospectively predicts the development of panic attacks and
related anxiety disorders. For instance, among non-clinical
adults with no history of panic, AS scores in the upper half
of the sample distribution were associated with a two-fold
increase in the likelihood of developing panic attacks, even
after controlling for trait anxiety (Schmidt, Zvolensky, &
Maner, 2006). Collectively, evidence across methodological
approaches indicates elevations in AS are reliably associated
with an increased likelihood of developing panic problems.
In the context of puberty, AS may represent a key vul-
nerability factor that may interact with the biopsychoso-
cial changes that occur during puberty to potentiate panic-
relevant learning. That is, compared to low AS youth, adoles-
cents with elevated AS may perceive the bodily events that
occur during puberty as personally threatening and anxiety-
provoking and thereby be exposed to more frequent and in-
tense learning trials, wherein they are learning to fear bodily
sensations, thereby setting the stage for panic development.
Over time, the repeated pairing of bodily sensations and anx-
iety about such sensations may result in a learned association
between these two phenomena, such that bodily sensations
ultimately come to elicit fear-relevant affective states. This
conceptualization is drawn from contemporary theoretical
models of panic development, where bodily sensations be-
come associated with fearful responding, ultimately resulting
in the development of anxious reactivity to such sensations
J Abnorm Child Psychol (2006) 34:799812
(Barlow, 2002; Bouton, Mineka, & Barlow, 2001). Although
theoretically promising, empirical tests of this perspective
are scant.
The objective of this investigation was to examine the
interaction between pubertal status and AS in predicting
anxious responding to a voluntary hyperventilation chal-
lenge among psychologically healthy adolescents. A bio-
logical challenge procedure was utilized because it allows
for a controlled, real-time assessment of multimodal (e.g.,
self-report; physiological) responding. This approach elim-
inates exclusive reliance on self-report, which, particularly
in regard to the reporting of emotional states/processes, is
subject to recall biases and other types of reporting er-
rors (McNally, 1999). In addition, this procedure: 1) has
been safely used with youth in the past (Unnewehr et al.,
1996), 2) is a non-invasive challenge controlled voluntar-
ily by participants, 3) produces responses that remit imme-
diately upon return to normal breathing, and 4) is a rec-
ommended treatment strategy for children and adolescents
with PD (Bouchard, Mendlowitz, Coles, & Franklin, 2004).
Moreover, prospective research indicates respiratory-based
challenges do not increase risk of panic-type problems (e.g.,
Harrington, Schmidt, & Telch, 1996; Perna, Cocchi, Politi, &
Bellodi, 1997; Prenoveau, Forsyth, Kelly, & Barrios, in
press). Overall, the potential gains in knowledge far out-
weigh the temporary discomfort that may result from study
procedures.
Three hypotheses guided the investigation. First, in terms
of predicting post-challenge self-reported anxiety, a main
effect of AS was expected. A main effect of pubertal status
on post-challenge anxiety was not predicted because the-
oretically, the changes associated with puberty would not
be expected to potentiate panic responding among healthy
adolescents per se, but rather only among those already at
risk by virtue of elevated levels of AS. Therefore, it was
expected that pubertal status would predict post-challenge
anxiety among adolescents high in AS, whereas pubertal
status would demonstrate less of a relation to such anxiety
among individuals low in AS.
Second, we conducted a discriminative test of our primary
hypothesis. Specifically, we examined the specificity of the
AS x pubertal stage interaction for predicting panic-type
responding versus general levels of negative affectivity. This
analysis aimed to provide an initial test of whether, given
support for our first hypothesis, the interaction between AS
and pubertal status is predictive of panic-type responding
specifically, or whether pubertal youth high in AS are at an
increased risk for negative affect in general. This test seemed
particularly relevant in light of established relations between
pubertal status and negative affectivity (e.g., Brooks-Gunn
et al., 1994). It was not expected that the AS x pubertal
status interaction term would relate to self-reported levels of
negative affectivity. Finally, for the purposes of generating
801
new research in this domain, we conducted some exploratory
analyses of physiological reactivity to the hyperventilation
challenge (i.e., changes in heart-rate).
Method
Participants
Adolescents between the ages of 12 and 17 years (M =
15.04; SD = 1.49) were recruited from the general commu-
nity. The primary means of advertising was flyers that alerted
adolescents to a study being conducted at a northeastern
university that involved a breathing exercise, an interview,
completion of questionnaires, and compensation for partic-
ipation. These fliers were placed in the community (e.g., in
arcades, primary care offices, adolescent-oriented commu-
nity centers) and advertisement booths also were set up in a
local well-traveled marketplace on two separate occasions,
approximately two months apart.
One hundred twenty four adolescents (57 females) par-
ticipated in the present study.1 The racial distribution of
the sample reflected that of the local population (State of
Vermont Department of Health, 2000): 90.3% (n = 112)
Caucasian; 3.2% (n = 4) African American; 0.8% (n = 1)
Native Hawaiian; 0.8% (n = 1) Asian; 0.8% (n = 1) Amer-
ican Indian; 0.8% (n = 1) other; and 3.2% (n = 4) did
not specify race. On average, participants had completed 9.91
years of education (SD = 1.56). Parents (Mage = 46.44 [SD:
5.99]; 91 females) provided additional demographic data
for 113 participants; 97 respondents were currently married
or living with someone; 1 was widowed, 12 were divorced
or separated, and 3 were never married. In terms of total
family income, 20 reported less than $50,000/year; 52 be-
tween $50,000 and $100,000/year; 21 between $101,000 and
1
In light of the sensitive nature of questions on the Tanner stage ques-
tionnaire, participants were reminded before completing the question-
naire battery that they were free to skip any questions that made them
feel uncomfortable. Of the 151 adolescents recruited, 124 completed
the Tanner stage questionnaire. Analyses indicated that there were no
significant differences between adolescents who completed the Tan-
ner stage questionnaire and those who did not with respect to age,
gender, anxiety sensitivity, or challenge responding.To delimit unnec-
essary participant burden, adolescents were apprised of exclusionary
criteria upon contacting the laboratory. Specifically, it was explained
that participants would be excluded for any of the six conditions de-
scribed in the narrative (e.g., if a doctor ever diagnosed you with a
mental health problem or gave you medication for it or if you have
a bad cold right now). Thereafter, the participant was asked whether
he/she was still interested in the study. Thirty-three adolescents (17 fe-
males) who contacted the laboratory reported that they did not meet the
inclusionary criteria; specific reasons for ineligibility were not recorded
and no additional information (e. g., age) was gathered. An additional
nine participants (5 females) were excluded on the basis of ADIS-C
responses (primary diagnoses: 6 past or current depression; 2 social
phobia; 1 specific phobia).
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$150,000/year; 10 more than $150,000/year; and 10 did not
specify.
Participants were screened for psychopathology using the
Anxiety Disorders Interview Schedule for the Diagnostic and
Statistical Manual Fourth Edition (DSM-IV): Child Ver-
sion (ADIS-C; Silverman & Albano, 1996). This standard-
ized assessment strategy allows for the clinical evaluation of
Axis I psychopathology related to anxiety and mood states
and ensures a conservative evaluation of the exclusionary cri-
teria. Research personnel were trained to mastery in the use
of the instrument; training involved intensive didactic ses-
sions, direct observation of administrations, and diagnostic
comparison until 100% diagnostic reliability was reached.
In addition, ongoing supervision (e.g., to resolve diagnostic
questions) was provided throughout the study. In addition,
medical history was assessed with a brief semi-structured
screening interview (e.g., Do you have asthma?) that we
developed and used successfully in previous work with ado-
lescents (Leen-Feldner et al., 2005). Based upon their re-
sponse to the ADIS-C, none of the participants had current
or past Axis I psychopathology. Additional exclusionary cri-
teria for the present study included: (a) current or past car-
diopulmonary (chronic) illness (e.g., chronic obstructive pul-
monary disease; asthma); (b) current acute respiratory illness
(e.g., bronchitis); (c) current or past psychotropic medication
use; (d) suicidality; and (e) limited mental competency and
the inability to give informed, written consent/assent. Such
exclusionary criteria have been used successfully in past bi-
ological challenge work with adults (Feldner et al., 2006),
and aside from avoiding medical complications and risks that
might arise from the procedure, they serve to reduce potential
confounds introduced by individual difference factors known
to affect responding to the hyperventilation procedure.
Measures
Pre-challenge assessment
The 18-item Childhood Anxiety Sensitivity Index (CASI;
Silverman, Fleisig, Rabian, & Peterson, 1991), a modifi-
cation of the adult 16-item Anxiety Sensitivity Index (Reiss,
Peterson, Gursky, & McNally, 1986), was used to assess AS.
Participants rated their perceptions of the aversive nature
of anxiety symptoms by endorsing 1 (none), 2 (some), or
3 (a lot) in response to questions such as it scares me when
my heart beats fast. This scale was adapted for, and validated
with, a population of children and adolescents. The scale has
good psychometric properties (e.g., Cronbachs alpha for the
total scale in present sample = 0.82) and satisfactory valid-
ity estimates (Silverman et al., 1991).
The Tanner staging system was selected as the index of pu-
bertal status. Although there is no gold standard in terms
of measuring pubertal development (Hayward, 2003), the
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J Abnorm Child Psychol (2006) 34:799812
Tanner stages provide a reliable index of secondary sexual
characteristics and, as such, reflect the two major hormonal
events associated with pubertal onset; adrenarche and go-
nadarche (Fechner, 2002). This approach is standard in pu-
berty assessment and is more reliable than other methods
(e.g., retrospective recall of menarche). Broader develop-
mental indices (e.g., age) were not used because they do not
necessarily reflect pubertal status (e.g., age at pubertal onset
varies across youth, for instance, female breast development
typically begins anywhere from ages 8 to 13; Tanner, 1962)
and hence, are not necessarily valid tools in the assessment
of puberty (Dorn, Dahl, Woodward, & Biro, 2006). Sub-
jects provided ratings of pubertal stage based on the Tan-
ner staging system (Morris & Udry, 1980). Each participant
was shown sex-appropriate drawings depicting specific sec-
ondary sexual characteristics across the course of puberty
(i.e., breasts and pubic hair in girls; genitalia and pubic hair
in boys). Participants were asked to choose the drawing that
most looks like you from each set of five drawings. Self-
ratings were averaged to generate a single score ranging
from Tanner stage I (immature) to Tanner stage V (mature)
for each participant. This instrument is commonly used in
puberty research (e.g., Hayward et al., 1992; Wilson et al.,
1991) and data support the validity of this assessment strat-
egy. For instance, Duke, Litt, & Gross (1980) reported good
convergent validity between this measure and physician rat-
ings of pubertal stage, with kappa coefficients ranging from
0.81 to 0.88. In terms of construct validity, self-reported
Tanner stage is positively correlated with physiological pro-
cesses known to occur during puberty, such as increases in
sex steroid concentrations (reflected by increased levels of
Insulin-Like Growth Factor I; Wilson et al., 1994) . Cron-
bachs alphas for the current sample are: Female Drawings =
.74; Male Drawings = .71.
The negative affectivity subscale of the Positive and
Negative Affect Schedule for Children (PANAS-C; Wilson,
Gullone, & Moss, 1998) was used to assess a generalized
propensity to experience negative affectivity. For each of 15
descriptors on the PANAS-C, participants were instructed
to indicate to what extent you usually feel this way, that
is, how you feel on average on a 5-point Likert-type scale
(1 = very slightly to 5 = extremely). The PANAS-C
was selected as the outcome variable for the discriminant
test in the current study because it is nonspecific; it covers a
wide range of negative affective states (e.g., anxiety; sadness;
anger). As such, it represents a particularly conservative test
of the study hypothesis that AS and pubertal status will re-
late specifically to panic-type states and not to general levels
of negative affectivity. In addition, the PANAS-C is psycho-
metrically sound; it demonstrates good internal consistency
(e.g., = .80 for the negative affectivity scale in the present
sample), as well as adequate discriminant and convergent
validity (Joiner, Catanzaro, & Laurent, 1996).
J Abnorm Child Psychol (2006) 34:799812
Challenge assessment
Self-reported anxiety was indexed using a Subjective Units
of Distress Scale (SUDS; Wolpe, 1958), which ranged from
0 (no anxiety) to 100 (extreme anxiety), and was ad- the right to discontinue participation at any time without
ministered during a baseline period and immediately post-
challenge. This is a well-established assessment of self-
reported anxiety in studies with adolescents (e.g., Pine et al.,
2000). Psychophysiological responding was indexed using a
J & J Engineering I-330-C2 system, which recorded phys-
iological data on-line at a sample rate of 1024 samples per
second across all channels using J & J Engineering Physiolab
Software. Raw electrocardiogram data were collected with
disposable Ag/AgCl electrodes placed in a standard bilateral
configuration on the palmar side of each wrist. Respiration
rate (breaths-per-minute) was sampled using a Pnemograph
sensor cable with two elastic PS-2 sensors filled with con-
ductive fluid. Stretching across the sensors causes a voltage
change, thereby providing a gross measure of excursion of
the chest during respiration. Respiration rate was examined
to validate the efficacy of the breathing rate manipulation.
As is standard in our laboratory, physiological data were
screened for outliers prior to data analysis.
Laboratory Challenge
A well-established voluntary hyperventilation procedure was
selected as the challenge induction because this laboratory-
based procedure allows for the modeling of panic-like expe-
riences (e.g., abrupt increases in bodily arousal) in a safe and
well-controlled manner (see Zvolensky & Eifert, 2000, for
a discussion). Specifically, this procedure has been shown
to be reliable and safe when used with children and adoles-
cents (Leen-Feldner et al., 2005; Unnewehr et al., 1996), its
parametric properties are well studied, and it reliably pro-
duces bodily arousal that mimics anxiety and panic attack
symptoms (Hornsveld, Garssen, Dop, & van Spiegel, 1990).
The challenge involved a three-minute hyperventilation with
a breathing rate of 30 respiratory cycles/min; this rate has
been shown to produce a decrease in pCO2 , an elevation in
blood pH, and increases in plasma epinephrine and lactate
levels (Fried & Grimaldi, 1993). To ensure consistency of
breathing rates across the duration of the interval and across
subjects, audiotaped instructions were used to standardize
participant breathing tempo (see below for details).
General Laboratory Layout and Procedure
The current study was approved by the University Insti-
tutional Review Board and ethical guidelines for research
with children and adolescents were adhered to throughout
all stages of the project. Specifically, informed written con-
sent (for child participation) from parents and written assent
from adolescents was obtained upon arrival at the labora-
803
tory. As part of the informed consent/assent process, partic-
ipants and parental guardians were fully informed about the
side effects of the challenge procedure, including the pos-
sibility of having a panic attack, and that participants had
penalty (no participant withdrew from the study). Next, a
doctoral level graduate student, trained in administration of
the ADIS-C and directly supervised by Dr. Leen-Feldner,
conducted the medical exclusionary screenings and psychi-
atric interviews. Exclusionary criteria were rigorously as-
sessed, with any ambiguous responses (e.g., I dont know)
coded as a positive endorsement. Biological challenge pro-
cedures were conducted in accordance with comprehensive
and strict laboratory policies, which include in-depth and on-
going training in the safe use of the procedure. In addition,
challenge administrators were carefully trained in the man-
agement of adverse reactions. Specifically, participants were
told they may give a simple indicator (e.g., wave) if they
wish to stop the procedure. In this event, or if the adminis-
trator has any reason to believe the participant is becoming
upset (each participant is monitored throughout the proce-
dure via a closed-caption television system), the procedure is
stopped immediately. The administrator is trained in the use
of cognitive-behavioral methods of anxiety reduction (e.g.,
relaxation training) to help participants relax if they are upset
and participants do not leave the laboratory until they have
returned to a relaxed state. In addition, licensed child clin-
ical psychologists, housed in the University Psychological
Clinic across the hall from the laboratory, were on-hand to
offer consultation services if necessary. However, it is im-
portant to note that we did not have a single instance where
an adverse reaction occurred or consultation was necessary.
Eligible participants first completed the pre-experimental
assessments. Thereafter, participants were seated in the sub-
ject testing room; an 8ft 12ft sound attenuated experimen-
tal room. Electrodes were attached, the experimenter left the
subject testing room, and the participant sat quietly for a
five-minute adaptation/baseline period, which is consistent
with prior studies utilizing the hyperventilation procedure
with adolescents (e.g., Unnewehr et al., 1996), so that he/she
could adjust to the laboratory context. Audiotaped directions
were then played for participants that described the hyper-
ventilation procedure as follows:
You will now be guided through a deep breathing ex-
ercise. In this exercise, you will be asked to breathe in
and breathe out very deeply. The instructions will tell
you when you should breathe in and when you should
breathe out. Simply inhale when asked to breathe in,
and exhale when asked to breathe out making each
breath in as deep as possible and each breath out as
forceful as possible. It is important that you follow these
instructions as best as you can, and continue the exercise
until you are asked to stop and rest.
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Post-challenge SUDS (anxiety) ratings were collected
directly following the hyperventilation challenge and
physiological data were gathered continuously throughout
the adaptation and challenge periods. The subject and exper-
imenter rooms were equipped with a closed circuit television
so the experimenter could monitor participant behavior and
ensure that the depth of breathing was comparable for all
participants. Supporting the efficacy of the procedure, results
indicated that the hyperventilation challenge significantly in-
creased breaths per minute (Mbaseline = 18.31; SD = 2.15;
Mchallenge = 25.71; SD = 3.31; t = 20.20, p < . 01) from
baseline to challenge. At the end of the study, the partic-
ipant and his or her parental guardian were compensated
$50 for their efforts. In addition, all participants took part
in our comprehensive debriefing procedure, which included
defining anxiety sensitivity, psychoeducation about panic
and bodily sensations, and a newsletter describing specific
study findings and details about the scientific research pro-
cess (mailed to participants at the conclusion of data collec-
tion; the newsletter is available from the first author upon
request).
General Analytic Approach
Separate hierarchical multiple regression analyses were con-
ducted to examine the study hypotheses. The model was
divided into three levels: (1) gender, age, and baseline levels
of anxiety were entered at level one; (2) main effects (e.g., to-
tal CASI scores and Tanner stage) were entered at level two,
and (3) the interaction term was entered at level three. Each
variable that met criteria for entry into the model (p = .05 to
enter) was retained. Squared semi-partial correlations (sr2 )
were used as indices of effect size for those variables retained
in the equation (Cohen, 1988). Main effect variables were
mean-centered prior to computing product terms (Aiken &
West, 1991). Overall, this analytic approach provides a test
of incremental validity and ensures that any observed asso-
ciations between the interaction term and criterion variables
are above and beyond the variance accounted for by fac-
tors at levels one or two in the equation (Cohen & Cohen,
1983; Sechrest, 1963). In the case of significant interactions,
the form of the interaction was graphically depicted in ac-
cordance with the recommendations of Cohen and Cohen
(1983). Finally, based on recommendations of Holmbeck
(2002), post-hoc probing analyses were conducted on the
data to examine significant moderational effects.
In each model, age, gender, and pre-experimental anxiety
were selected as covariates on an a priori basis. Specifi-
cally, in line with our conceptualization and the approach
taken in previous reports (Graber, Seeley, Brooks-Gunn, &
Lewinsohn, 2004; Hayward et al., 1992; Rabian et al., 1999),
we viewed the isolation of the effects of the predictor vari-
ables relative to chronological age, participant gender, and
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J Abnorm Child Psychol (2006) 34:799812
individual differences in pre-challenge levels of anxiety as
theoretically important2 .
Results
Means and standard deviations for predictor and criterion
variables are reported in Table 1. CASI scores for the current
sample are consistent with previous findings (e.g., Kearney
et al., 1997; Silverman et al., 1991). For instance, scores ob-
served in the current study (M = 23.98; SD = 4.49) were
lower compared to youth with panic disorder (M = 34.58;
SD = 8.06), other non-panic anxiety disorders (M = 28.32;
SD = 9.73), and various psychiatric diagnoses (e.g., M =
28.07; SD = 7.01; Silverman et al., 1991), and similar to
unscreened, non-clinical samples (M = 26.53; SD = 5.81).
Post-challenge anxiety ratings and mean challenge heart rate
also were comparable to those observed in studies of youth
using similar methodologies (e.g., Unnewehr et al., 1996).
In terms of zero-order correlations among the predictor and
demographic variables (see Table 1), AS and Tanner stage
related positively to age, and Tanner stage related positively
to female gender. No other significant associations emerged
among predictor and demographic variables. In regard to
challenge responding, as predicted, AS related positively to
post-challenge anxiety ratings and Tanner stage was not sig-
nificantly correlated with this outcome variable. Also, there
were no significant relations among AS, Tanner stage, and
physiological responsivity to the challenge. Finally, in line
with expectations, pubertal status correlated positively with
negative affectivity (r = .32); AS also was related to this
variable. Notably, CASI scores and Tanner stage shared little
variance with one another (i.e., 3.6%), supporting the con-
ceptualization that they are each tapping distinct processes.
2
The current study is the first direct test of the relation between pu-
berty and panic-relevant responding among both male and female ado-
lescents. Although the specific events of puberty differ across gen-
ders (e.g., differences in the amount and type of hormones released;
Fechner, 2002), and the risk for internalizing-type problems is higher
for post-pubertal girls (Hayward & Sanborn, 2002), the current model
is predicated on the notion that the co-occurrence of bodily perturba-
tion and fearful reactivity to such sensations may potentiate panic-type
responding. These general features are characteristic of puberty across
the sexes (Buchanan et al., 1992), and therefore, we contend that the
role of puberty in panic attack development may be similar for males
and females. Indeed, Craske (2003) points out that the frequency of
prodromal panic symptomatology such as panic attacks does not dif-
fer as a function of gender; rather, girls are more likely to engage in
avoidance-type behavior, increasing the likelihood of panic disorder
development. Nonetheless, the role of gender is an important element
of the model that merits empirical attention. In the present study, we
were underpowered to test hypotheses in separate genders (a test of
the triple interaction was non-significant). Instead, we elected to treat
gender as a co-variate in this initial test of the model and highlight the
issue of gender as paramount for future research in the area.
J Abnorm Child Psychol (2006) 34:799812 805

Table 1 Descriptive Data for Predictor and Criterion Variables

Variable 1 2 3 4 5 6 7 8 9 M (SD)

Predictor Variables
1. Age (in years) .10 .03 .14 .28 .53 .09 .22 .35 15.04 (1.49)
2. Gender .10 .08 .05 .30 .15 .11 .10 57
3. Baseline anxiety (SUDS) ratings .12 .17 .02 .41 .01 .19 9.01 (16.47)
4. Baseline mean heart-rate .18 .12 .10 .56 .06 74.70 (9.36)
5. CASI total score .19 .25 .15 .40 23.98 (4.49)
6. Tanner stage .14 .07 .32 4.21 (.72)
Criterion Variables
7. Post-challenge anxiety (SUDS) ratings .08 .29 22.87 (20.42)
8. Mean challenge heart-rate .10 90.82 (14.02)
9. PANAS-C: negative affect subscale score 12.87 (4.15)

Note. N = 124. Gender was dummy coded (0 = male; 1 = female); the number listed for gender reflects number of girls in the sample; SUDS:
Subjective Units of Distress Scale (Wolpe, 1958); CASI: Child Anxiety Sensitivity Index (Silverman et al., 1991); Tanner stage: self-reported
Tanner stages of pubertal development (Morris & Udry, 1980; Tanner, 1962); mean challenge responding scores were derived by averaging heart-
rate across the three-minute challenge period; PANAS-C: Positive and Negative Affect Scale for Children; (Wilson et al., 1998). = p < .05,

= p < .01.

To assess the degree to which the hyperventilation chal-
lenge elicited self-reported anxiety and physiological arousal
we examined changes in SUDS ratings and heart rate.
Paired samples t-tests suggested baseline self-reported anx-
iety (M = 9.01, SD = 16.47) and heart rate (M = 74.70,
SD = 9.36) significantly increased in response to the hy-
perventilation challenge (M = 22.87, SD = 20.42; M =
90.82, SD = 14.02, respectively) period [t (self-reported
anxiety) = 7.56, p < .01; t (heart rate) = 16.12, p < .01].
These data suggest the hyperventilation procedure effec-
tively elicited a panic-relevant response.
Results of the regression analyses are presented in Table 2.
With respect to post-challenge SUDS (anxiety) ratings, the
predictor set at the first level in the model accounted for a
significant amount of variance (R2 = .19, p < .01). At this
level only pre-experimental anxiety was significantly associ-
ated with post-challenge anxiety ratings ( = .40, p < .01)
such that higher levels of pre-experimental anxiety predicted
higher levels of post-challenge anxiety. After controlling for
age3 , gender, and pre-experimental anxiety, the predictor set
at the second level in the model accounted for additional
variance (R2 = .05, p < .05). As predicted, there was a
main effect of AS on post-challenge anxiety ( = .18, p <
.05) such that increased CASI scores predicted increased
anxiety following the hyperventilation procedure. There was
3 affectivity (see Table 2).
A reviewer made the interesting suggestion that observed findings
may be due to the effects of age, rather than pubertal status. Specif-
ically, compared to younger youth, older adolescents may evidence
greater awareness of, and ability to report, interoceptive states and/or
be more sensitive to the demand characteristics of the testing situation.
To explore this alternative explanation, we examined the interaction
between anxiety sensitivity (AS) and age in predicting post-challenge
anxiety. After controlling for gender, pre-experimental anxiety, and the
main effects of AS and age, the interaction was not predictive of SUDs
anxiety ratings (R2 = .00, = .77, t = .62, p = .56).
no main effect of Tanner stage. At level three, the interac-
tion term accounted for additional variance (R2 = .03,
= .19, t = 2.27, p < .05, sr2 = .03). As can be seen in
Figure 1, the nature of the interaction was consistent with
prediction. Specifically, among individuals of advanced pu-
bertal stage, greater AS was associated with increased anx-
ious responding to the challenge, whereas pubertal status did
not appear as strongly related to anxiety ratings among in-
dividuals low in AS (see Figure 1). Post hoc probing of this
moderational effect indicated the simple slope for the low
AS regression line was not significantly different from zero
(t = .04, ns), whereas the simple slope for the high AS re-
gression line was significant (t = 2.78, p < .01; Holmbeck,
2002). These analyses support hypotheses, suggesting post-
challenge anxiety ratings are higher among adolescents at
more advanced pubertal stage when AS is also high.
Next, in regard to negative affectivity, predictors at level
one of the model accounted for a significant amount of vari-
ance (R2 = .13, p < .01). Here, only age related positively to
negative affectivity ( = .34, p < .01) such that increased
age predicted elevated levels of negative affectivity. Level
two of the model also was significant (R2 = .12, p <
.05); there was a main effect of AS ( = .34, p < .01) such
that increased CASI scores predicted increased negative af-
fectivity. There was not a main effect of pubertal status4 .
Finally, as predicted, the interaction did not predict negative
4
Post hoc exploration of the association between pubertal status and
negative affectivity indicated that when pubertal status was entered by
itself at level two of the model, it predicted negative affectivity above
and beyond variance accounted for by age and gender. However, as
can be seen in Table 2, when CASI scores were entered simultaneously
with pubertal status at level two, pubertal status no longer predicted
negative affectivity.

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806 J Abnorm Child Psychol (2006) 34:799812

Table 2 Anxiety Sensitivity,

Pubertal Status, and Heart-Rate R2 t (each predictor) sr2 p (F)
Change Predicting
Dependent Variable: Post-Challenge Anxiety Ratings
Post-Challenge Anxiety Ratings
and Negative Affectivity Step 1 .19 < .01
Age (in years) 1.33 .11 .01 ns
Gender 1.24 .11 .01 ns
Baseline Anxiety (SUDS) 4.72 .40 .16 < .01
Step 2 .05 < .05
CASI-total score 2.09 .18 .03 < .05
Tanner stage 1.62 .16 .02 ns
Step 3 .03 < .05
CASI-total score x Tanner stage 2.27 .19 .03 < .05
Dependent Variable: PANAS-C negative affectivity subscale total score
Step 1 .13 < .01
Age (in years) 3.89 .34 .11 < .01
Gender .85 .07 .00 ns
Step 2 .12 < .01
CASI-total score 4.00 .34 .11 < .01
Tanner stage 1.31 .13 .01 < .01
Step 3 .02 ns
CASI-total score x Tanner stage 1.92 .16 .02 ns
Dependent Variable: Post-Challenge Anxiety Ratings
Step 1 .18 < .01
Age (in years) 1.48 .12 .01 ns
Gender 1.08 .09 .00 ns
Baseline Anxiety (SUDS) 4.53 .39 .15 < .01
Step 2 .08 < .01
CASI-total score 1.95 .17 .02 < .05
Heart Rate Change 2.87 .24 .05 < .01
Note: N = 124. = Step 3 .03 < .05
standardized beta weight.
CASI-total score x Heart Rate Change 2.28 1.19 .03 < .05
Gender was dummy coded (0 =
male; 1 = female); SUDS: Dependent Variable: Post-Challenge Anxiety Ratings
Subjective Units of Distress Step 1 .18 < .01
Scale (Wolpe, 1958); CASI: Age (in years) 1.24 .10 .00 ns
Child Anxiety Sensitivity Index Gender 1.22 .10 .00 ns
(Silverman et al., 1991); Tanner Baseline Anxiety (SUDS) 4.45 .38 .14 < .01
stage: self-reported Tanner Step 2 .07 < .01
stages of pubertal development Tanner stage 1.81 .18 .02 ns
(Morris & Udry, 1980; Tanner, Heart Rate Change 2.52 .21 .04 < .05
1962); PANAS-C: Positive and
Step 3 .03 ns
Negative Affect Scale for
Tanner Stage x Heart Rate Change 1.55 .73 .01 ns
Children; (Wilson et al., 1998).

Theoretically-Derived Exploratory Analyses
Finally, we explored psychophysiological reactivity to the
challenge. Specifically, we examined AS and pubertal status
as independent moderators of the relation between heart-
rate change5 and post-challenge anxiety. The model with
5
We also examined the study hypotheses in terms of heart rate vari-
ability (HRV). Specifically, the J & J Engineering software we use
provides power values for the high frequency (HF) and low frequency
(LF) components of the power spectra; consistent with extant research
(e.g., Friedman & Thayer, 1998), HF power and the LF/HF ratio (as
an index of cardiac autonomic balance) were employed as the index
of HRV. Neither AS nor pubertal status moderated the association be-
the puberty by heart-rate change interaction term was non-
significant (see Table 2). However, in the AS model, the
predictor set at the first level accounted for a significant
amount of variance (R2 = .18, p < .01). At this level only
pre-experimental anxiety predicted post-challenge anxiety
ratings ( = .39, p < .01). After controlling for age, gen-
der, and pre-experimental anxiety, the predictor set at the
second level in the model accounted for additional variance
(R2 = .08, p < .05). There was a main effect of AS ( =
.17, p < .05) and heart-rate change ( = .24, p < .01);
these were qualified by a significant interaction at level three
tween challenge-related changes in HRV and anxious reactivity to the
voluntary hyperventilation.

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J Abnorm Child Psychol (2006) 34:799812
40
35
30
Post-Challenge SUDS Rating
26
25
20
17
15
10
0
Low Tanner
Tanner Stage
Fig. 1. Post-challenge anxiety ratings, as a function of pubertal status
(measured using the Tanner staging system; Morris & Udry, 1980) and
anxiety sensitivity (indexed via the Anxiety Sensitivity Index; Silver-
(R2 = .03, = 1.19, t = 2.28, p < .05, sr2 = .03). A
graphical depiction of the interaction is presented in Figure 2;
among youth who experienced a greater change in heart-rate
in response to the challenge, greater AS was associated with
increased anxious responding to the challenge, whereas heart
rate change did not appear as strongly related to anxiety rat-
ings among individuals low in AS (see Figure 2). Post hoc
probing of this effect supports this interpretation; the simple
slope for the low AS regression line was not significantly dif-
ferent from zero (t = .33, ns), whereas the simple slope
for the high AS regression line was significant (t = 3.47,
p < .01; Holmbeck, 2002).
Discussion
To date, no study has examined the interactive role of pu-
bertal status and AS in predicting panic vulnerability among
adolescents. The present study sought to address this gap
in the literature. As predicted, and consistent with the ex-
tant literature linking AS to a number of anxiety-relevant
outcomes (Silverman & Weems, 1999), total CASI scores
related positively to post-challenge anxiety ratings. Also
consistent with hypotheses, there was no main effect of pu-
bertal status on post-challenge anxiety. This supports our
contention that puberty per se does not increase panic re-
activity. Rather, pubertal stage interacted with AS such that
807
35.75
Low AS
High AS
16.58
High Tanner
man et al., 1991) among participants one-half of a standard deviation
above and/or below the mean for each predictor.
high AS adolescents endorsing more advanced pubertal sta-
tus reported the greatest overall post-challenge anxiety. In
contrast, pubertal status had relatively less of an effect on
low AS adolescents (see Figure 1). These findings support the
conceptualization that AS and pubertal status interact to in-
crease vulnerability to anxious responding to bodily arousal.
Thus, bodily changes related to puberty among youth with
pre-existing panic vulnerability (i.e., high AS), may provide
a critical context in which panic-relevant learning occurs
(Bouton et al., 2001). Interestingly, recent data suggest AS
relates positively to catastrophic misinterpretation of internal
somatic cues among youth in grades 3, 6, and 9 (Mattis &
Ollendick, 1997). Findings from the current study coalesce
well with these data; among adolescents high in AS, the
events of puberty may provide a fecund context for expe-
riencing fear in the context of somatic arousal, ultimately
setting the stage for a panic attack. Future research may
benefit by examining other features of puberty that may po-
tentiate panic development (e.g., timing; Graber, Lewinsohn,
Seeley, & Brooks-Gunn, 1997). Importantly, post-challenge
anxiety results cannot be attributed to Axis I psychopathol-
ogy or individual difference factors, including state anxiety,
age, and gender. Although the size of the observed effect
was small in overall magnitude at 3% of uniquely explained
variance, it is important to consider the larger context when
considering the potential significance of this finding. Specif-
ically, a relatively large amount of variance was explained
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808
60
50
Post-Challenge SUDS Ratings
40
30
20 19.75
10
0 0
Low Heart Rate Change
Change in Heart Rate
Fig. 2. Post-challenge anxiety ratings, as a function of heart rate
change (baseline to mean within-challenge heart rate) and anxiety sen-
sitivity (indexed via the Anxiety Sensitivity Index; Silverman et al.,
by predictor variables, including the covariates and the main
effect of AS, at earlier levels in the model (i.e., 24%); thus,
there was relatively less variance that could be accounted
for by the interaction term. In this sense, it is noteworthy
that the interaction term enhanced the models predictive
power (Abelson, 1985). In addition, we employed a vol-
untary hyperventilation challenge among psychologically
healthy adolescents, which likely truncated upper-end vari-
ability in panic-relevant responding. Utilization of prospec-
tive time-sampling methodologies to examine the interactive
roles of pubertal status, AS, and panic-relevant responding in
real-world contexts would further develop empirical un-
derstanding of how these factors relate across time during
puberty-related biopsychosocial development.
Next, as a test of specificity, we examined the predictor
variables in relation to self-reported negative affectivity. As
expected, the AS by pubertal status interaction was unrelated
to negative affectivity, suggesting these factors do not com-
bine to increase a general propensity to experience negative
affect, but rather are specifically related to anxious respond-
ing to bodily sensations. Such specificity tests are critical for
building sophisticated, developmentally-sensitive risk factor
models of panic psychopathology (Kraemer et al., 1997).
Of note, negative affectivity was indexed via self-report
and therefore future studies would benefit from measuring
this construct via multi-modal, multi-informant assessment
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J Abnorm Child Psychol (2006) 34:799812
55
Low AS
High AS
9.5
High Heart Rate Change
1991) among participants one-half of a standard deviation above and/or
below the mean for each predictor.
strategies. In terms of main effects, pubertal status corre-
lated positively with negative affectivity, although there was
no main effect in regression analyses. This latter finding
was surprising in light of theory and research suggesting pu-
berty is marked by increased negative affect (Brooks-Gunn
et al., 1994). However, post-hoc analyses (see Footnote #4)
suggested the absence of a main effect in regression analyses
was due to the fact that when AS was entered simultaneously
with pubertal status at level two of the model, it accounted
for much of the associated variance. Prior to drawing con-
clusions, this pattern of findings should be replicated among
a sample of adolescents with less stringent selection crite-
ria, which would delimit the impact of constrained variance.
In any case, these two sets of findings provide promising
initial results suggesting pubertal development and AS may
interact to specifically influence panic onset among youth.
In exploratory analyses focused on psychophysiological
reactivity to the challenge, the AS by heart-rate change inter-
action predicted post-challenge anxiety after accounting for
age, gender, baseline anxiety, and the respective main effects.
This analytic approach uniquely extends available work ex-
amining the main effect of AS on psychophysiological reac-
tivity, wherein null findings have been observed among both
youth (Leen-Feldner et al., 2005; Rabian et al., 1999) and
adults (Zvolensky, Feldner, Eifert, & Brown, 2001). The find-
ing that anxious responding was elevated among youth who
J Abnorm Child Psychol (2006) 34:799812
were both high in AS and had experienced relatively greater
change in heart-rate from baseline to challenge is consistent
with AS theory (e.g., Reiss, 1991), which suggests high AS
individuals find bodily perturbation to be fear-relevant. Con-
sistent with the interactionist perspective that puberty is un-
likely to be pathogenic in its own right (Graber, Petersen, &
Brooks-Gunn, 1996), the interaction between pubertal status
and heart-rate change did not predict post-challenge anxiety.
In this sense, the two sets of findings are complementary;
only the theoretically-relevant individual difference (AS),
and not pubertal status, combined with heart-rate reactivity
to predict challenge response. Extending these findings to
other indices of physiological arousal (e.g., cortisol levels)
would further bolster these conclusions.
A number of issues warrant further consideration. First,
the study was cross-sectional. While useful at this early stage
of research, this design does not permit causal inferences,
nor does it speak to changes in vulnerability processes across
time. Moreover, specific pubertal processes were not directly
investigated; much has yet to be learned regarding the par-
ticular events that occur during puberty, which may promote
panic-relevant learning. Second, this sample is limited as it
was a relatively homogenous (e.g., psychologically healthy,
primarily Caucasian) group of adolescents who volunteered
to participate for monetary reward and whose parents were
available/willing to transport them to the laboratory. To rule
out the potential role of self-selection bias among this sam-
ple and increase the generalizability of these findings, future
studies would benefit by examining a more diverse sam-
ple and utilizing alternative recruitment efforts. Third, the
present study used a controlled laboratory-based induction
of abrupt bodily sensations to allow for a multimodal (e.g.,
self-report; physiological) observation of panic-relevant re-
sponding in real-time. This approach represents a useful
laboratory model of panic-relevant responses, which allows
for insight into panic vulnerability, but does not reflect ac-
tual PD development. Accordingly, future research that inte-
grates both laboratory and naturalistic (prospective) methods
will ultimately provide the most comprehensive account of
the role of AS and puberty in panic development. Finally,
although an inspection of the non-significant interaction be-
tween AS and age predicting challenge response (see foot-
note #3) increased our confidence that findings from the
current study were not due to the effects of age, the specific
role of puberty (versus other age-related variables, such as
cognitive development) is a critical issue for future investiga-
tors to elucidate. Here, it will be important to obtain samples
that evidence variability in both age and Tanner stage (e.g.,
groups of youth ages 9, 10, and 11 at each of the five Tanner
stages; Hayward, 2003) and to directly examine theoretically
relevant cognitive variables such as anxiety-relevant memory
biases (e.g., Teachman, 2005).
809
From a clinical perspective, the current study is note-
worthy for two primary reasons. First, there are direct im-
plications for panic prevention, an important area receiving
burgeoning empirical attention (Craske & Zucker, 2002).
The value of well-controlled (e.g., laboratory-based) anxiety-
related risk factor research has been articulated within a
translational framework where risk factor research informs
prevention efforts and vice versa (Zvolensky et al., 2006).
This stage model of progress highlights studies of the inter-
play among risk factors as a critical step toward designing
effective preventative interventions for youth at risk for anx-
iety. As an illustrative example, given compelling (e.g., in-
dependently replicated and extended) evidence for the roles
of AS and pubertal development in the onset of panic psy-
chopathology, investigators could identify high AS adoles-
cents in a primary care setting who are just entering puberty
and design a brief intervention aimed at reducing AS. Al-
though in its relative infancy, research with adults suggests
such an approach may be effective (Schmidt et al., in press).
Here, a key research objective will be to empirically estab-
lish cut-offs that indicate at what level of AS the risk for
panic development meaningfully increases (Bernstein, Zv-
olensky, Stewart, Comeau, & Leen-Feldner, 2006). This type
of criterion would enhance prevention-related efforts by de-
lineating specific subpopulations at risk for developing panic
(Feldner, Zvolensky, & Schmidt, 2004). Second, there are in-
direct implications of the current findings for work with clin-
ical populations of adolescents suffering from panic prob-
lems. Specifically, researchers are now situated to extend
these findings to clinical samples of adolescents with panic
disorder to begin to understand if AS and pubertal status may
be involved in the maintenance or exacerbation of such prob-
lems. Overall, the present study sets the stage for additional
research targeted at disentangling the specific mechanisms
that impact panic problems among youth.
Acknowledgements This project was supported by a grant from
Child & Adolescent Research and Training, Inc. awarded to the
first author and National Institute on Drug Abuse research grants
(1 R01 DA018734-01A1, R03 DA16307-01, and 1 R21 DA016227-
01) awarded to the sixth author. The authors thank Kate Follansbee,
Marc Hartigan, Justin McCormick, Amanda ODell, Stephanie Sinisi,
and Lindsay Van Zanten for their assistance with this project.
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