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Changes in Caffeine States Enhance Return of Fear in Spider Phobia


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Treatment of phobias is sometimes followed by a return of fear. Animal and human research has shown that changes in external and internal contexts between the time of treatment and follow-up tests often enhance return of fear. The present study examined whether shifts in caffeine (C) state would enhance return of fear. Participants who were highly afraid of spiders (n = 43) were treated in 1-session exposure-based therapy and tested for follow-up 1 week later. Participants were randomly assigned to 1 of 4 groups and received either placebo (P) or C at treatment and follow-up sessions: CC, PP, CP, and PC. Results demonstrated state-dependent learning. Participants experiencing incongruent drug states during treatment and follow-up (CP and PC) exhibited greater return of fear than those experiencing congruent drug states (CC and PP).
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Changes in Caffeine States Enhance Return of Fear in Spider Phobia
Jayson L. Mystkowski, Susan Mineka, Laura L. Vernon, and Richard E. Zinbarg
Northwestern University
Treatment of phobias is sometimes followed by a return of fear. Animal and human research has shown
that changes in external and internal contexts between the time of treatment and follow-up tests often
enhance return of fear. The present study examined whether shifts in caffeine (C) state would enhance
return of fear. Participants who were highly afraid of spiders (n 43) were treated in 1-session
exposure-based therapy and tested for follow-up 1 week later. Participants were randomly assigned to 1
of 4 groups and received either placebo (P) or C at treatment and follow-up sessions: CC, PP, CP, and
PC. Results demonstrated state-dependent learning. Participants experiencing incongruent drug states
during treatment and follow-up (CP and PC) exhibited greater return of fear than those experiencing
congruent drug states (CC and PP).
Exposure-based treatment approaches have an excellent record
of efficacy in the treatment of specific phobias (e.g., Barlow, 1988;
Craske, 1999). This approach involves controlled in vivo exposure
to anxiety-provoking stimuli (e.g., Craske & Rowe, 1997; O
1997). In addition to mere exposure, therapists often model non-
fearful behavior when in the presence of a phobic stimulus (e.g., a
tarantula) and encourage participant imitation for each treatment
task. Many (but not all) studies have shown support for the
superiority of treatments that include the following beneficial
elements: in vivo versus imaginal exposure, graded as opposed to
ungraded exposure, and participant modeling (e.g., Bandura, Blan-
chard, & Ritter, 1969; Foa & Kozak, 1986; Marks, 1987).
In spite of the marked efficacy of exposure therapy in reducing
fears and phobias, some fear may return with the passage of time
since treatment. Specifically, return of fear, which is analogous to
Pavlov’s (1927) spontaneous recovery phenomenon, is the “reap-
pearance of fear that has undergone partial or complete extinction”
(Rachman, 1989, p. 147). The partial fear recovery may emerge
either between exposure sessions or after a long follow-up period.
The underlying mechanisms of return of fear have proven dif-
ficult to isolate. To date, researchers have examined treatment
variables (e.g., intensity or duration of exposure trials), posttreat-
ment variables (e.g., stressful life events that occur after treatment
and before retesting at follow-up), and individual difference vari-
ables during treatment (e.g., level of state arousal) that might
predispose certain individuals to greater return of fear as assessed
either through heart-rate or self-reported levels of fear. However,
as reviewed by Craske (1999), none of the variables examined in
these three broad categories have been shown to affect return of
fear in a reliable fashion. Thus, although there are a number of
different factors, both during and after treatment, that may influ-
ence the return of fear, these are yet to be determined and verified
empirically in a consistent manner.
Within the last 2 decades, new research in animals has examined
the effects of changes in context on return of fear and provided
new insights into possible determinants of return of fear in hu-
mans. This work on return of fear in animals has been inspired by
significant work in animals and humans on contextual control of
learning and memory more generally. Specifically, Bouton and
colleagues (e.g., Bouton, 1988, 1991, 1994; Bouton & Bolles,
1979; Bouton & Nelson, 1998) have provided strong evidence that
partial fear recovery
occurs in rats when a conditioned stimulus
(CS) that was extinguished or counterconditioned in one context
(other than the one where acquisition occurred) is later presented
in a different recovery context. Having similarity across extinction
and recovery contexts, on the other hand, prevents or minimizes
fear recovery (Bouton & King, 1983). According to Bouton
(1993), when a discrepancy between extinction and recovery con-
texts occurs, contextual cues favor the retrieval of memories as-
sociated with fear acquisition rather than the memories of extinc-
tion. Bouton’s work with rats suggests the importance of studying
contextual cues in human fear extinction because it has potentially
important implications for treatment of phobias and quite possibly
other anxiety disorders as well.
Recently Rodriguez, Craske, Mineka, and Hladek (1999) at-
tempted to determine whether similar fear recovery effects occur
in humans by examining the effects of changes in external context
on return of fear in spider-fearful participants following their
successful treatment 2 weeks earlier of spider fear using a live
tarantula as the fear-provoking stimulus. The results provided only
Fear recovery is the term used most often in animal research, whereas
return of fear is the term used most often in human research. The two terms
are equivalent.
Jayson L. Mystkowski, Susan Mineka, Laura L. Vernon, and Richard E.
Zinbarg, Department of Psychology, Northwestern University.
Jayson L. Mystkowski is now at the Department of Psychology, Uni-
versity of California, Los Angeles. Laura L. Vernon is now at the De-
partment of Psychology, Auburn University.
We thank the undergraduate research assistants that helped with all
phases of this study and Beverly Rodriguez for her very careful training
and supervision of these individuals in the exposure therapy procedures.
We also thank William Revelle and Kris Anderson for the advice concern-
ing the caffeine manipulation and in interpreting the EA and TA results of
the effects of caffeine in our study.
Correspondence concerning this article should be addressed to Susan
Mineka, Department of Psychology, Northwestern University, Evanston,
Illinois 60208. E-mail:
Journal of Consulting and Clinical Psychology Copyright 2003 by the American Psychological Association, Inc.
2003, Vol. 71, No. 2, 243–250 0022-006X/03/$12.00 DOI: 10.1037/0022-006X.71.2.243
weak support for the hypothesized effects of change of context on
return of fear, with heart-rate data in only one of the two relevant
conditions indicating greater return of fear in the group experienc-
ing a context shift than in the group experiencing no context shift.
Self-report results were not significantly affected by the same
manipulation; such desynchrony among different measures of fear
in studies of fear extinction is quite common (see Craske, 1999, for
a review). There were, however, two potentially important meth-
odological confounds that may have contributed to the relative
lack of significant results in this study (see Mineka, Mystkowski,
Hladek, & Rodriguez, 1999; Rodriguez et al., 1999, for discussion
of these limitations).
Therefore Mineka et al. (1999) modified the Rodriguez et al.
(1999) study design, attempting to make the necessary method-
ological changes to avoid these confounds. One important change
was increasing the distinctiveness of the different contexts relative
to those used by Rodriguez et al. Another important change in-
volved conducting follow-up testing in a completely novel context
that had not previously been encountered by the participants. (In
the Rodriguez et al. study, participants had previously been ex-
posed to the follow-up context with the tarantula present, prior to
treatment). Both of these changes enhanced external validity be-
cause individuals who encounter a phobic stimulus after therapy
are probably at least as likely to do so in novel and very distinctive
contexts as in contexts where they have previously encountered
their phobic stimulus (as in the Rodriguez et al. study). Highly
spider-fearful participants participated in a two-session study
(treatment and follow-up 1 week later). Results confirmed that
treatment was highly effective in decreasing fear. Moreover, par-
ticipants tested in a novel context at follow-up showed a greater
return of fear than participants tested in the same context as where
treatment had occurred. Nevertheless, it should be noted that the
observed effects were not as large as those seen in the animal-
conditioning literature. Mystkowski, Craske, and Echiverri (2002)
also found similar context shift effects using a within-groups
design in which all participants were tested in both the same and
a different context (in this case indoors and outdoors).
Beyond these significant yet preliminary results pertaining to
the effects of changing external contexts on return of fear in
humans, there is some experimental evidence from both animals
and humans suggesting that contexts are not limited to physical
settings. For an example particularly relevant to the current topic,
Bouton (1988, 1993) found that internal states/cues may also
enhance retrieval of memories associated with conditioning or
extinction, thus affecting a rats response to a previously extin-
guished stimulus. In particular, Bouton, Kenney, and Rosengard
(1990) found evidence in rats for context specificity of fear ex-
tinction using internal contexts (drug state) induced by diazepam
versus placebo (P). Following extinction of a fear CS in one drug
state, rats that were later tested for fear of the CS in a different drug
state (P vs. diazepam) showed greater return of fear than those
tested in the same drug state as during extinction. On the basis of
these findings, Bouton suggested that extinction of fear may be
specific to the drug context in which it occurs and that mismatch
of internal states experienced during treatment and follow-up can
lead to significant return of fear (Bouton & Swartzentruber, 1991).
Related results were reported by Cunningham (1979) using alcohol
rather than diazepam as an internal context.
Such findings using drug states as internal contexts in studies of
context specificity of fear extinction are one example of a more
general phenomenon known as state-dependent learning, which
can be defined as a decrement in learned performance after a shift
in physiological state. State-dependent learning has been investi-
gated primarily in learning of nonemotional responses (e.g., Over-
ton, 1978; Spear, 1973; see Craske, 1999, for a review) but also
occurs with regard to the retention of learning with emotional
content, particularly with regard to the retention of extinction, in
both humans and nonhuman animals (e.g., Bouton et al., 1990;
Gray, 1987; Marks, Viswanathan, Lipsedge, & Gardner, 1972).
One example particularly relevant to the current study was that
of Marks et al. (1972), who exposed situational phobics to fear-
provoking situations under one of two different drug conditions:
diazepam 4 hr before treatment withP1hrbefore treatment or P 4
hr before treatment with diazepam 1 hr before treatment. Marks et
al. found that individuals in the 4-hr diazepam condition (where
the drugs anxiolytic effects were likely to be decreasing during
exposure therapy) had greater transfer of treatment gains when
later tested in a nondrug state than those receiving diazepam 1 hr
before treatment. Although Marks et al.s study design did not use
the 2 2 design needed to demonstrate the full state-dependent
learning effect (which would require a group treated with the 4-hr
diazepam condition and tested with diazepam and a group treated
with the 1-hr diazepam condition and tested under diazepam), the
results of the study were nonetheless consistent with the state-
dependent learning phenomenon.
Rather than focusing on state-dependent learning effects with
anxiolytic medications, the current study focused on whether state-
dependent learning effects in extinction also can be demonstrated
using caffeine (C)a very widely used drug that is reliably anx-
iogenic, at least in patients with generalized anxiety disorder,
social phobia, and panic disorder (e.g., Boer, 2000; Bruce, Scott,
Shine & Lader, 1992; Simmons, 1996). This is also an important
practical issue from a clinical standpoint given that the majority of
people treated for anxiety disorders undoubtedly ingest C from
time to time. This may sometimes occur before a treatment session
and is, in fact, likely to occur sometime during long-term follow-
up. Although there are no published accounts that we are aware of
on state-dependent learning in anxious individuals using C, Lowe
(1987, 1988) conducted a 2-day study of unselected participants
that examined the interaction of common social drugs on state-
dependent learning on a cognitive task. Results showed a signifi-
cant decrement in recall from the cognitive task in those partici-
pants who did not ingest C before the start of both the learning and
recall test sessions; no significant declines in recall emerged when
C was administered across both sessions.
On the basis of the results reflecting Cs effect on state-
dependent learning and on anxiety in individuals with anxiety
disorders, the clinically relevant question is simply whether
changes in C state affect return of fear (or potentially the short-
term effectiveness of treatment as well). Thus, the effects of
internal context on return of fear were investigated by manipulat-
ing drug state through C versus P ingestion in a one-session
exposure-based therapy and then again at follow-up, approxi-
mately 1 week later. We hypothesized that the results would
demonstrate state-dependent learning, with participants experienc-
ing incongruent drug states (C/P and P/C) exhibiting a signifi-
cantly greater return of self-reported fear (measured during a
behavioral approach task) from posttreatment to follow-up than
those participants experiencing congruent drug states (C/C and
Forty-three fearful participants (33 women, 10 men) were selected from
introductory psychology classes at Northwestern University using the
31-item Spider Questionnaire (Klorman, Hastings, Weerts, Melamed, &
Lang, 1974)
administered during a 1st-week mass testing session. Initially
participants were chosen from those in the top 20% of the distribution for
this questionnaire; scores ranged from moderate to extreme fear (range:
1527, M 18.28, SD 3.63). In addition, participants reported that they
exhibited moderate avoidance of spiders (on a 08 point scale, M 4.70,
SD 2.03), as well as moderate impairment of functioning (on a 08 point
scale, M 3.37, SD 2.21). The participants were primarily college
freshmen of Caucasian background. Prior to the treatment session, partic-
ipants were informed of the nature of the study and of possible C con-
sumption that day. Five potential participants were excluded for the fol-
lowing reasons: refusing treatment, failing to complete treatment in the
time allotted, or displaying insufficiently strong fear during an initial
behavioral approach task (BAT). The primary criterion for insufficiently
strong fear was a participant reporting a fear level below 70 during the
pretreatment BAT, as measured by the Subjective Units of Distress Scale
(SUDS; Wolpe, 1973) on a 1100 range. However, those participants who
had an initial fear level between 60 and 70 but refused to touch the spider
when prompted to do so (n 5) were included because their behavioral
avoidance was significant in spite of slightly lower levels of reported fear.
The SUDS included the following anchors 0 no fear,25 mild fear,
50 moderate fear,75 strong fear, and 100 extreme fear. Partici-
pants were given class credit for their participation in both sessions of the
study; Session 1 (treatment) lasted up to 3 hr and Session 2 (follow-up)
lasted 1 hr.
On arrival, participants were assigned to one of four groups according to
the experiments2 2 between-groups factorial design: CC (n 11), PP
(n 11), CP (n 10), and PC (n 11). Although assignment to groups
was initially random, about halfway through the experiment, we noticed
that pretreatment levels of fear during the first BAT were not equivalent
across groups. To remedy this problem thereafter, we used a matching
procedure whereby a qualified participants group assignment was based
on how many other participants in that group were in different parts of the
fear range during the initial BAT.
During the BATs and during treatment, the primary measure of self-
reported fear was the widely used SUDS described previously. Before and
after treatment and at follow-up, participants also completed a question-
naire that measured spider beliefsthe Spider Phobia Beliefs Question-
naire (SBQ; Arntz, Lavy, van den Berg, & van Rijsoort, 1993).
The two
subscales of this questionnaire, given before each BAT, assessed a partic-
ipants thoughts about spiders and how they believed they would react in
the presence of a spider.
To monitor changes in arousal, specifically energetic and tense arousal,
we administered 40 items from Thayers ActivationDeactivation Adjec-
tive Checklist (AD-ACL; 1978, 1986) during each session before the first
exposure to the tarantula and again just before the postdrink BAT, which
occurred 0.5 hr after C or P had been ingested. Thayers AD-ACL is highly
reliable and has two core dimensions: energetic arousal (EA; lively, alert)
and tense arousal (TA; anxious, fearful). C, relative to P, reliably increases
both EA and TA as a linear function of increasing the dose of C from 0 to 4
mg/kg body weight (Anderson, 1994).
Experimental settings for the study included an instruction room and a
therapy room. Both were well lit and contained tables, chairs, and wall
decorations. One large, nonpoisonous Chilean Rose-Haired tarantula
(Phrixotrichus spatulata; legspan approximately 6 in. [15.2 cm]) served as
the phobic stimulus. In the therapy room, several exposure task items,
including garden and latex gloves, paintbrushes, and a small open container
for the tarantula were used. The tarantula was housed in a plastic cage with
an easily removable top.
To manipulate the internal state of the participants by a double-blind
procedure, we prepared two solutions (C citrate and a similar tasting P
solution of flat quinine water) and randomly designated them as either A or
B for the experimental therapist, who did not know whether A or B was C.
In reality, A was C and B was quinine. Participants were told that they
might or might not receive C. The amount of A or B solution administered
to a participant was set at 4 mg per kg of body weight or the equivalent
amount of C contained in three cups of coffee. Body weight was deter-
mined by self-report. A juice mixture, orange-flavored Tang (Kraft Foods),
was then used to mask the taste of both solutions.
There were four (one male, three female) highly trained undergraduate
research assistants who were used as experimental therapists. The research
assistants received in-depth training with a treatment manual and were
supervised by a graduate student with several years of experience in
treating spider phobia. Before completing training, each research assistant
had to practice with 23 practice participants under the close scrutiny of the
supervising graduate student.
The study consisted of two sessions separated by approximately 1 week:
Session 1 (treatment) and Session 2 (follow-up). On arrival, participants
were escorted to an instruction room where they were instructed about the
standardized nature of the experimental and treatment procedures and then
asked to give formal written consent to participate in the study. They also
completed an information sheet to indicate their degree of avoidance and
impairment caused by their spider fear (using two 08 point scales). Then,
participants were trained to use the SUDS for rating their level of fear/
anxiety throughout the course of the study. Next, participants completed
the SBQ (SBQ 1) and the AD-ACL (AD-ACL 1), followed by the pre-
treatment BAT (BAT 1).
For BAT 1, the tarantula was in its home cage, a small open container
on a table situated in one corner of the therapy room. Participants were
asked to quickly approach and touch the tarantula if they were able to do
so, or, if not, to touch the bottom of the container, or if not able to do either,
to approach as closely as possible, reporting the peak amount of fear they
were experiencing using the 0100 point SUDS. Both the approach dis-
tance (measured in feet from the spider) and fear level were recorded by the
experimenter. The furthest approach distance was 13 ft (3.96 m), whereas
the closest distance was touching the spider with a fingertip. Following this
task, participants were given a 5-min rest period in the instruction room
(for details, see Rodriguez et al., 1999).
Following BAT 1, participants ingested the drink associated with their
assigned experimental condition (A or B) in the instruction room and
completed filler questionnaires and read magazines for 30 min. Participants
then completed the AD-ACL again (AD-ACL 2) and participated in a
second BAT (BAT 2) in the therapy room, identical to the first BAT, to
assess possible differential changes in fear caused by C or P ingestion. A
5-min rest period followed the avoidance task and preceded exposure
Klorman et al. (1974) reported the Spider Questionnaire to have high
internal consistency (
s .83 to .90).
The two subscales (Spider Beliefs and Responses to Spiders) have
shown high internal consistency (
.94) and significant testretest
reliability, r(25) 0.68 to 0.84; Arntz et al., 1993.
Exposure-based treatment was the longest part of Session 1. Participants
were escorted to the therapy room, given the treatment rationale, and asked
to rate the perceived credibility of the proposed 14-step treatment, which
consisted of a standard fear hierarchy (for details, see Rodriguez et al.,
1999). The experimenter explained and modeled each task for the partic-
ipant. Participants then performed the task and were periodically prompted
to rate their fear levels. The task was terminated when the participants fear
was reduced to mild levels, corresponding to 25 or less on the 100-point
scale. Treatment was considered complete if the participants reached the
14th step in the hierarchy (holding the tarantula in their bare hand). The
total amount of time allotted to treatment was 1.5 hr. On completing
treatment, participants were brought back to the instruction room where
they completed the SBQ 2.
Participants then engaged in a posttreatment BAT (BAT 3) in the
treatment room. During this BAT, participants were first asked to return to
the BAT 1 distance (the closest they had been able to approach on the first
BAT) and to rate their fear level. Next, participants were asked to proceed
further and touch the tarantula (2 were unable to do so and they rated their
fear at the closest point that they could reach). At each approach distance,
participants were asked to rate their fear level on the 100-point scale. The
approximate time to complete Session 1 was 3 hr.
One week later, participants participated in the hour-long follow-up
session. Participants were given a brief description of the procedures for
the final part of the study, as well as a review of the SUDS, and they also
completed SBQ 3 and AD-ACL 3. (Because the SBQ 3 was administered
before the C/P manipulation it was not expected to be sensitive to state-
dependency effects.) Meanwhile, the experimental therapist, who remained
blind, prepared the C/P solution according to each participants group
assignment. Participants were then given the juice drink and instructed to
read magazines for 30 min. Following this 30-min period, participants
completed AD-ACL 4 and engaged in another BAT (BAT 4) in the therapy
room. During the BAT 4, participants first reported their fear level at their
BAT 1 distance, at their BAT 3 distance, and, if they had not touched the
tarantula at BAT 3, they were prompted to do so and to report their fear
level at that closer approach distance for BAT 4. These were the only
dependent measures used for testing the state dependency hypothesis. As
before, approach distances and maximum fear levels were recorded by the
experimenter. This was followed by a 5-min rest period.
Finally, participants completed an exit interview assessing their thoughts
about the experiment and were then debriefed. Experimenters made sure
that participants were not anxious or highly aroused when leaving the
Data Analytic Strategy
To account for potential pretreatment differences between those partic-
ipants who ingested C and those who did not, the amount of change in
self-reported fear from the pretreatment BAT (BAT 1) to postdrink BAT
(BAT 2) was calculated and used as a covariate in the following analyses
that examined self-reported fear during BATs.
To examine treatment effectiveness and return of fear on our measures
of self-reported fear and spider phobic cognitions, we conducted analyses
of trend on the repeated measures factor focusing on the linear trend as an
index of the overall effectiveness in reducing fear from pretreatment
through follow-up and then examined the quadratic trend as an index of
return of fear.
Treatment Effectiveness
Initially four mixed-design analyses of covariance (ANCOVAs)
were conducted, focusing on the primary dependent measure of
self-reported fear during the BATs, to determine whether (a) the
two groups tested after treatment and follow-up in the same drug
state showed comparable patterns of fear reduction at both the
initial and the final approach distances and (b) the two groups
tested after treatment and follow-up in different drug states showed
comparable patterns of fear reduction at both the initial and final
approach distances. These four mixed design ANCOVAs with 2
groups (AA vs. BB or AB vs. BA) 4 (pretreatment, postdrink,
posttreatment, and follow-up repeated measures)
indicated that
treatment was highly effective in decreasing levels of self-reported
fear when participants were asked to approach a tarantula during a
In particular, a 2 groups (AA vs. BB) 4 repeated measures
ANCOVA with an analysis of trend on the repeated measures
factor at the initial approach distance (closest distance attained at
the pretreatment BAT, such as standing near the spiders con-
tainer) revealed a significant downward linear trend for SUDS
scores, from BATs 14, for those participants under the same drug
state (i.e., AA and BB) at treatment and follow-up, F(1, 17)
884.77, p .0001. There was no significant difference between
these groups in their rates of fear reduction, expressed by the lack
of a Group Linear Trend interaction, at the initial approach
distance, F 1. A parallel ANCOVA for the final approach
distance (closest distance attained at the posttreatment BAT, usu-
ally touching the spider) revealed the same significant downward
linear trend, F(1, 18) 312.89, p .0001, without a Group
Linear Trend interaction, F 1. Similarly, the 2 groups (AB vs.
BA) 4 repeated measures ANCOVAs with analyses of trend on
the repeated measures factor also revealed a significant downward
linear trend for those participants under different drug states at
treatment and follow-up (i.e., AB and BA), F(1, 17) 104.93, p
.0001, for the initial approach distance, F(1, 17) 31.06, p
.0001, for the final approach distance. There were no significant
Group Linear Trend interactions, indicating no differences
between these two groups in their rates of fear reduction at either
the initial approach distance, F(1, 17) 2.56, p .128, or the
final approach distance, F 1. Finally, all but 1 of the participants
(n 42) were able to hold the tarantula in their bare hand by the
end of treatment, with the 1 participant only being able to touch the
tarantula with a fingertip by the end of the treatment session. This
participants data were included since touching the tarantula with
a fingertip was the closest approach distance possible during the
posttreatment and follow-up BATs.
Because none of these four ANCOVAs (two for AA vs. BB and
two for AB vs. BA) revealed any significant Group Downward
Linear Trend interactions at either approach distance from the
pretreatment to the follow-up BATs, participants in groups AA and
BB were pooled into the Same group and participants in groups
AB and BA were pooled into the Different group in order to
maximize the power of subsequent analyses.
As expected after merging the four groups into the two afore-
mentioned groups, a 2 groups (Same vs. Different) 4 (pretreat-
ment, postdrink, posttreatment, and follow-up repeated measures)
mixed design ANCOVA with an analysis of trend on the repeated
measures factor revealed significant declines in levels of self-
reported fear at the initial and final approach distances from the
For these analyses, initial and final approach distances were the same
for BATs 1 and 2.
pretreatment to the follow-up BATs. Specifically, at the initial
approach distance, there was a significant downward linear trend
for groups, F(1, 37) 454.75, p .0001, that did not interact with
group assignment, F 1. Moreover, at the final approach distance,
there were also significant decreases in self-reported fear from
pretreatment to follow-up, as indicated by a significant downward
linear trend, F(1, 38) 171.27, p .0001, that did not interact
with group assignment, F(1, 38) 1.77, p .191. (See Table 1
and Figures 1 and 2.) Thus the overall effectiveness of treatment
from pretreatment to follow-up did not differ in the Same and
Different groups.
With regard to the two subscales of spider phobic cognitions
(SBQ), 2 groups (Same vs. Different) 3 (pretreatment, posttreat-
ment, and follow-up repeated measures) mixed-design ANOVAs
with analyses of trend on the repeated measures factor indicated
that exposure therapy reduced phobic thoughts about spiders as
indicated by a significant downward linear trend, F(1, 39)
149.55, p .0001, as well as thoughts about how one might react
when in the presence of a spider as indicated again by a significant
downward linear trend, F(1, 39) 58.08, p .0001. However,
there were no significant differences by group or Group Down-
ward Linear Trend interactions observed for either type of phobic
cognitions: F(1, 39) 2.85, p .100, for phobic thoughts, F 1,
for reactions to spiders (see Table 2).
Return of Fear
To examine possible differential return of fear from BAT 3 to
BAT 4 1 week later, we examined the results for the quadratic
trends from the two groups by four repeated measures ANCOVAs
described previously. There was a significant quadratic trend in
self-reported fear from pretreatment to follow-up while at the final
approach distance, F(1, 38) 8.13, p .007. Moreover, there was
a significant interaction between groups (Same vs. Different) and
the quadratic trend at the final approach distance, F(1, 38) 5.19,
p .028. Examination of the interaction indicated that there was
more self-reported return of fear in those participants under dif-
ferent drug states at treatment and follow-up than there was in
those with consistent treatment and follow-up drug states. This
same quadratic trend was not observed at the initial approach
distance, F 1; nor was there a significant interaction between
group and the quadratic trend at the initial approach distance,
F 1 (see Table 1 and Figures 1 and 2).
Mixed-design ANCOVAs also indicated reliable quadratic
trends in phobic thoughts about spiders and in thoughts of how one
might react when exposed to a spider, Fs(1, 39) 82.88
and 58.08, respectively, both ps .0001. There were no signifi-
cant interactions of group with these quadratic trends, Fs 1.
However, as noted above, this is not surprising given that the
SBQ 3 was administered before the C/P ingestion manipulation.
Predictors of Return of Fear
A simultaneous multiple regression analysis, collapsing across
all four groups, of various pretreatment, treatment, and posttreat-
ment variables (e.g., initial fear level and phobic cognitions about
the stimulus, treatment credibility and total treatment time, and
posttreatment fear level and phobic cognitions, respectively) was
conducted to determine predictors of return of fear (other than
context) at both the initial and final approach distances. Although
overall there was very little return of fear at the initial approach
Table 1
Self-Reported Fear During Behavioral Approach Tasks (BATs):
Adjusted Means
M 74.35 67.20 12.90 19.57 15.15 20.81
SD 10.87 17.87 11.28 15.87 13.51 16.24
M 80.30 68.50 16.75 17.85 18.00 31.75
SD 14.89 18.57 24.88 21.16 20.55 33.10
Note. Because of missing data, the Subjective Units of Distress Scale
(SUDS) values of 20 Group Same and 20 Group Different participants
were used to determine the adjusted means at the initial approach distance,
and the SUDS values of 21 Group Same and 20 Group Different partici-
pants were used to determine the adjusted means at the final approach
distance. SUDS1 SUDS recorded at the pretreatment BAT; SUDS2
SUDS recorded during postdrink BAT; SUDS3A SUDS recorded during
the posttreatment BAT at the initial approach distance; SUDS3B SUDS
recorded at the posttreatment BAT at the final approach distance;
SUDS4A SUDS recorded during the posttreatment BAT at the initial
approach distance; SUDS4B SUDS recorded at the posttreatment BAT
at the final approach distance.
Figure 1. Self-reported fear levels (SUDS) at initial approach distance
(measured during BAT 1) at pretreatment (Pre-Tx), postdrink, posttreat-
ment (Post-Tx), and follow-up.
Figure 2. Self-reported fear levels (SUDS) at final approach distance
(measured during BAT 3) at pretreatment (Pre-Tx), postdrink, posttreat-
ment (Post-Tx), and follow-up.
distance, the regression analysis indicated that high levels of
self-reported fear at the posttreatment BAT (BAT 3) predicted
return of fear (change from BAT 3 to BAT 4) at the follow-up
BAT (BAT 4) at the initial approach distance,
.662, R
F(1, 37) 22.39, p .0001, but not at the final approach distance.
No other predictors were significant at either approach distance.
Effects of C
The expected differential effects of C versus P on changes in
self-reported arousal received only very limited support in this
investigation. A great deal of prior research using the same dose of
C on unselected participants has shown that those given C show
EA and TA scores significantly higher than those given P 30 min
following ingestion of the drink (n 2,730; d .46 for EA, and
d .37 for TA; W. Revelle, unpublished data, personal commu-
nication, June 20, 2001). By contrast, the two P groups and the two
C groups in the present study did not differ at postdrink, EA:
t(39) 0.95, p .35, d .30; TA: t(39) ⫽⫺0.09, p .93, d
.03. Moreover, in our study both C and P groups demonstrated
only a very slight increase in TA and a very slight decrease in EA
from the pretreatment AD-ACL (AD-ACL 1) to postdrink AD-
ACL (AD-ACL 2). Participants in both C groups (AA and AB)
during Session 1 exhibited a very slightly larger increase in TA
(pretreatment: M 14.05, SD 3.72; postdrink: M 14.95,
SD 6.07; ⌬⫽0.90), than those participants in the P groups (BB
and BA) during Session 1 (pretreatment: M 14.35, SD 6.62;
postdrink: M 15.11, SD 5.33; ⌬⫽0.76). With regard to EA
during Session 1, there was a slightly smaller decrease in mean EA
in the C groups (pretreatment: M 14.25, SD 6.87; postdrink:
M 14.10, SD 7.15; ⌬⫽⫺0.15) than in the P groups
(pretreatment: M 12.90, SD 6.50; postdrink: M 11.93,
SD 7.40; ⌬⫽⫺0.97). Mixed design ANOVAs failed to reach
significance for any of the observed mean differences, Fs 1.
This failure to find expected significant increases in both EA
and TA for C groups in the present study seems primarily attrib-
utable to the fact that all our participants started with significantly
higher baseline EA and TA before consumption of either drink
than observed in prior studies with unselected participants about to
be studied on simple cognitive tasks. Specifically, in Revelle and
Andersons prior research (e.g., Anderson, 1994; Anderson &
Revelle, 1994), levels of EA and TA in their P participants were
significantly lower than in our study, t(1856) 2.20, p .025 for
TA, d .35, and t(1900) 2.42, p .010 for EA, d .38. Such
baseline elevations in our study are undoubtedly attributable to the
increased anticipatory anxiety that spider fearful participants
would be expected to experience when anticipating being treated
for their spider fear shortly.
In agreement with previous literature on the effectiveness of
exposure therapy for specific phobias, this investigation demon-
strated that graded exposure-based therapy with participant mod-
eling is highly effective in significantly reducing behavioral avoid-
ance, self-reported fear levels, and phobic beliefs pertaining to
spiders. Moreover, it also demonstrated that C ingestion per se
does not appear to reduce the efficacy of exposure therapy for at
least some specific phobias. Of more importance, however, the
results from this investigation confirmed our state-dependency
hypothesis regarding return of fear. Participants tested under con-
sistent drug states from treatment to follow-up exhibited signifi-
cantly less return of fear (at the final approach distance) than
participants tested under inconsistent drug states. This study also
extended prior work in humans (e.g., Marks et al., 1972) and
animals (e.g., Bouton et al., 1990) by showing that similar effects
to those obtained with anxiolytic drugs can be obtained with Ca
somewhat anxiogenic drug. In addition, these data replicate and
extend the previous work by Rodriguez et al. (1999), Mineka et al.
(1999), and Mystkowski et al. (2002), as well as extant findings in
the animal conditioning literature (e.g., Bouton, 1988, 1991, 1993,
1994; Bouton & Bolles, 1979; Bouton & Nelson, 1998), whereby
changes in external context from treatment to follow-up retention
tests lead to increased return of fear. Together, these results lend
further support to the notion that changes in context (including
internal drug state) from treatment to follow-up serve to enhance
return of fear among individuals receiving treatment for specific
fears and phobias.
One possible limitation of the present study is that the state-
dependency hypothesis was only supported at the final approach
distance. In several other studies on this topic using same or
different external contexts, results have been significant at the
initial approach distance. However, it seems quite possible that the
initial approach distance would not be as sensitive a measure in the
present experiment, where the physical context used during treat-
ment and follow-up for the Different groups was the same, as it is
when the physical context changes from treatment to follow-up for
Different groups as in Mineka et al. (1999) and Mystkowski et al.
(2002). That is, the effects of change in drug state may be manifest
most fully when one is about to encounter the feared stimulus itself
rather than at some relatively arbitrary physical place where one
had stopped during the very first behavioral approach task (and
that physical place is identical during follow-up).
Another possible limitation of the present study is that changes
in levels of TA and EA did not differ significantly between the C
and P participants on the AD-ACL. Specifically, participants in the
C group did not demonstrate a significant increase in either EA or
TA following C ingestion as anticipated; nor did their arousal
levels following C ingestion differ significantly from those in the
P groups (although all group differences were in the expected
Table 2
Spider Phobic Beliefs
M 50.15 17.07 13.26 25.49 7.48 4.85
SD 17.58 14.45 8.76 20.32 10.58 6.39
M 45.92 15.43 15.91 29.91 8.60 9.22
SD 21.62 10.74 15.23 21.45 9.74 13.64
Note. Spider Phobia Beliefs Questionnaire (SBQ) values of 22 Group
Same and 21 Group Different participants were used to determine the
means for SBQ1A and, due to missing data, the SBQ values of 21 Group
Same and 21 Group Different participants were used to determine the
remaining means. A thoughts about the spider; B what do you think
your response to the spider will be? 1 recorded before treatment; 2
recorded after treatment; 3 recorded at follow-up.
directions). This is in spite of the fact that the same C dose and
ingestion procedure was used here that has previously generated
significant increases in TA and EA, as well as significant differ-
ences from P groups. Although it is possible that we did not have
an adequate sample size to detect reliable differences, we do not
think this is the most likely explanation of our failure to observe
reliable changes in EA and TA. Instead, we think the more likely
explanation of our failure to observe hypothesized increases in
arousal stems from the already increased state of arousal that our
fearful participants were experiencing at the outset of the experi-
ment. Specifically, the prior studies demonstrating these C effects
used unselected participants about to participate in an information
processing study, who presumably were not in a state of anticipa-
tory anxiety (Anderson, 1994; Anderson & Revelle, 1994). Our
participants, by contrast, were all highly fearful of spiders and
knew that they had arrived at an experiment in which they were to
be treated for their fear. Consistent with this, participantsbaseline
levels of TA and EA were significantly higher than in the studies
conducted by Anderson (1994) and Anderson and Revelle (1994;
Revelle, personal communication, June 20, 2001). Moreover, the
postingestion measures of EA and TA also occurred 30 min
following the first BAT, which means that residual arousal from
the BAT itself could have obscured possible arousal differences
due to C.
Because changes in C state are the only reasonable explanation
for the state-dependent results exhibited in this investigation, it
seems likely that the AD-ACL is simply not sensitive enough to
detect additive effects of arousal stemming from C ingestion and
arousal stemming from the frightening nature of the anticipated
experimental tasks. Thus the AD-ACL does not seem to be an
adequate measure of state arousal induced by C when studying
participants selected as being highly fearful of an object or situa-
tion they are about to encounter. Whether there are other measures
of arousal that are more capable of reliably differentiating between
various sources of arousal among fearful individuals about to
encounter their feared objects remains to be determined.
Results of this study support the idea that state-dependent ef-
fects of C can influence return of fear in human participants treated
for spider phobia. As such, they complement and extend other
studies examining the effects of anxiolytic drugs on the outcome of
behavioral or cognitivebehavioral treatment for other anxiety
disorders. In addition to the study of Marks et al. (1972) on
state-dependent return of fear using diazepam in situational pho-
bics discussed previously, Marks et al. (1993) found related results
in an important study of behavioral and anxiolytic drug treatment
of agoraphobics. Using a 2 2 design, four groups of agorapho-
bics were treated for 8 weeks with (a) alprazolam and exposure
therapy, (b) P and exposure therapy, (c) alprazolam and relaxation
training (conceived as a less active therapy condition), or (d) P and
relaxation training. Medications were then tapered over an 8-week
period and assessments were continued for approximately 27 more
weeks. Results indicated that the group treated with alprazolam
and exposure showed a significantly higher relapse rate than the
group treated with P and exposure, supporting the state-dependent
learning phenomenon with anxiolytic drugs and exposure therapy
in a sophisticated large scale study of these issues in the treatment
of agoraphobia.
The issues raised by the two Marks et al. (1972, 1993) studies
and those presented here are important for two reasons. First,
significant numbers of people undergoing behavioral treatment for
anxiety disorders receive a combination of anxiolytic medication
and behavioral treatment, and withdrawal from the medications
can clearly enhance return of fear. Second, fluctuations in C state
are also very common over the course of treatment, and follow-up
and such fluctuations may also enhance return of fear. Moreover,
one might also expect that among those who combine anxiolytic
medication and behavioral treatment with regular or irregular C
use, fluctuations in fear levels following exposure therapy might
be especially likely. However, further research will be necessary to
corroborate this hypothesis, and it would be particularly important
to test this hypothesis in a treatment-seeking clinical sample to
determine the generalizability of our results.
In conclusion, the most specific implication of our study is that
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conduct some but not all exposure sessions after drinking a caf-
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exposure therapy in a variety of contextsboth internal and
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Received August 29, 2001
Revision received January 20, 2002
Accepted January 30, 2002
... Memory impairment and inability to memory retrieval are two main symptoms of several psychological disorders, such as post-traumatic stress disorder (PTSD), anxiety, depression, and stress-related disorders (Radulovic et al. 2018). Also, SDM has implications for the effectiveness of psychological treatment on psychiatric patients (Mystkowski et al. 2003). Moreover, the alcoholic subjects or opioid addicts are more susceptible to impairment of memory and retrieval. ...
Full-text available
Rationale Tramadol and ethanol, as psychoactive agents, are often abused. Discovering the molecular pathways of drug-induced memory creation may contribute to preventing drug addiction and relapse. Objective The tramadol- and ethanol-induced state-dependent memory (SDM) and cross-SDM retrieval between tramadol and ethanol were examined in this study. Moreover, because of the confirmed involvement of GABAA receptors and GABAergic neurotransmission in memory retrieval impairment, we assessed cross-SDM retrieval between tramadol and ethanol with a specific emphasis on the role of the GABAA receptors. The first hypothesis of this study was the presence of cross-SDM between tramadol and ethanol, and the second hypothesis was related to possible role of GABAA receptors in memory retrieval impairment within the dorsal hippocampus. The cannulae were inserted into the hippocampal CA1 area of NMRI mice, and a step-down inhibitory avoidance test was used to evaluate state dependence and memory recovery. Results The post-training and/or pre-test administration of tramadol (2.5 and 5 mg/kg, i.p.) and/or ethanol (0.5 and 1 g/kg, i.p.) induced amnesia, which was restored after the administration of the drugs 24 h later during the pre-test period, proposing ethanol and tramadol SDM. The pre-test injection of ethanol (0.25 and 0.5 g/kg, i.p.) with tramadol at an ineffective dose (1.25 mg/kg) enhanced tramadol SDM. Moreover, tramadol injection (1.25 and 2.5 mg/kg) with ethanol at the ineffective dose (0.25 g/kg) promoted ethanol SDM. Furthermore, the pre-test intra-CA1 injection of bicuculline (0.0625, 0.125, and 0.25 μg/mouse), a GABAA receptor antagonist, 5 min before the injection of tramadol (5 mg/kg) or ethanol (1 g/kg) inhibited tramadol- and ethanol-induced SDM dose-dependently. Conclusion The findings strongly confirmed cross-SDM between tramadol and ethanol and the critical role of dorsal hippocampal GABAA receptors in the cross-SDM between tramadol and ethanol.
... Another main interest in applying inhibitory retrieval to sport is that it makes exposure therapy more efficient when applied to dynamic changing environments, such as sport competition. Indeed, research has revealed that the CR can show "spontaneous recovery" (e.g., the return of the original fear response) when the CS-noUS has been trained in a limited number Maximizing exposure therapy in sport 7 of contexts while the athlete undergoes exposure therapy (Culver et al., 2011;Mystkowski et al., 2002Mystkowski et al., , 2003Mystkowski et al., , 2006Olatunji et al., 2017). In other words, fear extinction is specific to the context in which the extinction is being trained. ...
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ABSTRACT Physical exercise is considered as a promising medication free and cost-effective adjunct treatment for substance use disorders (SUD). Nevertheless, evidence regarding the effectiveness of these interventions is currently limited, thereby signaling the need to better understand the mechanisms underlying their impact on SUD, in order to reframe and optimize them. Here we advance that physical exercise could be re-conceptualized as an “interoception booster”, namely as a way to help people with SUD to better decode and interpret bodily-related signals associated with transient states of homeostatic imbalances that usually trigger consumption. We first discuss how mismatches between current and desired bodily states influence the formation of reward-seeking states in SUD, in light of the insular cortex brain networks. Next, we detail effort perception during physical exercise, and discuss how it can be used as a relevant framework for re-dynamizing interoception in SUD. We conclude by providing perspectives and methodological considerations for applying the proposed approach to mixed design neurocognitive research on SUD.
... Another main interest in applying inhibitory retrieval to sport is that it makes exposure therapy more efficient when applied to dynamic changing environments, such as sport competition. Indeed, research has revealed that the CR can show "spontaneous recovery" (e.g., the return of the original fear response) when the CS-noUS has been trained in a limited number Maximizing exposure therapy in sport 7 of contexts while the athlete undergoes exposure therapy (Culver et al., 2011;Mystkowski et al., 2002Mystkowski et al., , 2003Mystkowski et al., , 2006Olatunji et al., 2017). In other words, fear extinction is specific to the context in which the extinction is being trained. ...
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Inhibitory retrieval has redefined the way that exposure therapy can help individuals cope with debilitative states of fear and anxiety. Here we propose that an inhibitory retrieval-based model of exposure therapy could also be applied to the context of sport competition. We first discuss the usefulness of applying inhibitory retrieval-based exposure to emotion regulation in sport environments and provide therapeutic strategies for adopting this approach for athletes with performance anxiety and states of fear of failure. This proposal is followed by a case description that illustrates how this inhibitory retrieval approach could be used to help athletes get better at coping with fear and anxiety during a sport competition. We conclude by providing further guidelines for helping practitioners apply the inhibitory retrieval approach while working with athletes who experience debilitative states of anxiety during sport competition. Lay summary: This theoretical and case study paper discusses the application of inhibitory retrieval-based exposure for helping athletes who experience dysfunctional states of anxiety during competition. Inhibitory retrieval-based exposure aims to assist the athletes in creating new experiences when confronted with the pressure of sport competition. Here we aim to describe in detail how inhibitory retrieval-based exposure could be applied to sport environments by providing therapeutic strategies for adopting this approach for athletes with performance anxiety and states of fear of failure. • IMPLICATIONS FOR PRACTICE • Inhibitory retrieval-based exposure helps athletes cope with states of debilitative anxiety. • This approach should also help athletes focus on optimal ways to perform under anxiety. • Inhibitory retrieval-based exposure should reinvigorate the athlete-environment dynamic.
... On the other hand, the agoraphobic situation reflects a boundary condition (a context) for the additional association between bodily sensations and threat (context-depending extinction learning). However, generalization of cue associated inhibitory learning processes to varying contexts was demonstrated to be limited (Culver, Stoyanova, & Craske, 2011;Mineka, Mystkowski, Hladek, & Rodriguez, 1999;Mystkowski, Craske, & Echiverri, 2002;Mystkowski, Craske, Echiverri, & Labus, 2006;Mystkowski, Mineka, Vernon, & Zinbarg, 2003;Rodriguez, Craske, Mineka, & Hladek, 1999). In line, we also found substantial residual fear responses during post-treatment BAT assessment in the patients of the T-group. ...
Further developments of exposure-based therapy (EBT) require more knowledge about transfer of treatment to non-trained everyday contexts. However, little is known about transfer effects of EBT. Using a standardized EBT protocol in 275 patients with panic disorder and agoraphobia we investigated the transfer of EBT to a highly standardized context during a Behavioral Avoidance Test (BAT; being entrapped in a small and dark test chamber) and not part of the exposure sessions. Patients of a treatment group underwent the BATs before treatment (t1), after a preparatory treatment phase (t2), and after an agoraphobic exposure phase (t3) and were compared with wait-list control patients, who repeated BAT assessments across the same time period. We found stronger reductions in avoidance behavior, reported fear, and autonomic arousal during the BAT from t1 to t3 in the treatment group patients who were anxious during t1 relative to the anxious but untreated patients. Fear reduction was related to treatment outcome indicating the contribution of transfer effects to successful EBT. Interestingly, reduction varied for different fear response systems suggesting different processes to may be involved in transfer effects. Importantly, final BAT assessment still evoked residual fear in the treatment group as compared to BAT non-anxious control patients, suggesting limited transfer effects – one possible reason for the return of symptoms in new situations.
... Context plays an important role in occasioning both adaptive and maladaptive behaviors; indeed, for both operant and extinction research demonstrates that a change in context after learning may result in a decrement in performance of the new learning (Bouton & Todd, 2014;Todd, Winterbauer & Bouton, 2012). Context changes can include both external and internal cues (Bouton, 2002;Mystkowski, Craske, & Echiverri, 2002;Mystkowski, Mineka, Vernon, & Zinbarg, 2003), and have been identified as a potentially important source of relapse across both avoidance related and appetitive disorders (M. W. Otto, O'Cleirigh, & Pollack, 2007;Thomas, Larsen, & Ayres, 2003). ...
Low income and low educational attainment are among the strongest predictors of both smoking prevalence and lapse (i.e., return) to smoking after cessation attempts. Treatment refinement is limited by inadequate knowledge of the specific lapse- or relapse-relevant vulnerabilities characteristic of populations that should be the target of treatment. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the role of 2 specific lapse-relevant targets relative to the higher stress characteristic of low-socioeconomic contexts: low distress tolerance and low working memory capacity. Furthermore, we use an innovative approach for understanding risk of smoking lapse in smokers undergoing a quit attempt to examine candidate mechanistic targets assessed not only during nicotine use, but also during the conditions smokers will face upon a cessation attempt-during stressful nicotine-deprivation windows. This study is designed to show the incremental value of assessments during deprivation windows, in part because of the way in which specific vulnerabilities are modified by, and interact with, the heightened stress and withdrawal symptoms inherent to nicotine-deprivation states. Specifically, the study is designed to evaluate whether a novel mindfulness intervention (mindfulness combined with interoceptive exposure) can improve upon existing mindfulness interventions and extend therapeutic gains to the modification of mechanistic targets assessed in high-stress or negative affectivity contexts. The overall goal is to validate mechanistic targets and associated interventions for the purpose of expanding treatment options for at-risk smokers. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
... However, two studies Wiederhold et al., 2002) found that feedback of the heart rate did enhance the effect of ET, while one study could not find an influence of (visual or tactile) feedback (Tardif et al., 2019). Mystkowski et al. (2003) showed that the "caffeine state", i.e. how much coffee a participant drank, has an effect on post-ET anxiety in that a "caffeine state" differing to the one in the ET lead to greater return of fear. ...
Although Exposure Therapy (ET) is the first-line treatment of Specific Phobia (SP), there is no clear consensus on which factors influence its success, and thus on how to conduct it most efficiently. This review summarizes the current state of research regarding this topic. N = 111 studies were in accordance with our eligibility criteria: participants had at least symptoms of SP, the intervention was ET and the study investigated a factor influencing its success. Best evidence for positive effects was found for low trait anxiety, high motivation and high self-efficacy before the ET, high cortisol levels and heart rate variation, evoking disgust additionally to anxiety, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs. These factors may be conceptualized as modulating different aspects of learning as suggested in current models of ET that focus on inhibitory learning mechanisms. Limitations lie in the great heterogeneity concerning operationalization of factors and success. Based on these findings, we make suggestions for improvements in ET conduction and which factors should be researched in the future.
... The return of fear seen in both scenarios suggests that retrieval of the inhibitory CS-no US memory formed during extinction is relatively context specific, as even in a novel context that is ambiguous with regard to safety, the memory of the CS-US pairing tends to prevail [55]. Importantly, the range of possible contextual changes leading to renewal is wide, from physical location of training [56] to virtual reality environments [57] and internal states such as being caffeinated [58]. ...
Full-text available
Laboratory models of extinction learning in animals and humans have the potential to illuminate methods for improving clinical treatment of fear-based clinical disorders. However, such translational research often neglects important differences between threat responses in animals and fear learning in humans, particularly as it relates to the treatment of clinical disorders. Specifically, the conscious experience of fear and anxiety, along with the capacity to deliberately engage top-down cognitive processes to modulate that experience, involves distinct brain circuitry and is measured and manipulated using different methods than typically used in laboratory research. This paper will identify how translational research that investigates methods of enhancing extinction learning can more effectively model such elements of human fear learning, and how doing so will enhance the relevance of this research to the treatment of fear-based psychological disorders.
... Similarly, it is important to note that the generalizability which occurred in the followup assessment was operationalized through temporal and contextual changes. These changes have been found elsewhere to predict a higher fear renewal (Mystkowski, Mineka, Vernon, & Zinbarg, 2003;Vansteenwegen et al., 2007). Future studies may expand on the current work, and explore the extent to which similarly augmented exposures may generalize to changes in stimulus itself. ...
Our recent trial demonstrated individuals suffering from social anxiety with performance-related concerns who received virtual reality exposure augmented with scopolamine, a cholinergic antagonist, experienced significantly less post-treatment context renewal (CX) than placebo (Craske et al., 2019). The purpose of the present investigation was to determine who specifically benefits from scopolamine by examining hippocampal (HPC) functioning as a moderator of treatment response (Placebo n = 15, SCOP 0.5 mg n = 15, SCOP 0.6 mg n = 15). Skin conductance response to conditional stimulus (SCR-to-CS) termination suggested a dose-response relationship for enhanced HPC functioning individuals, wherein individuals receiving scopolamine demonstrated less fear at CX. In addition, SCR-to-CS onset indicated reduced fear at CX for impaired HPC individuals receiving SCOP 0.5 mg and SCOP 0.6 mg relative to Placebo. Our findings, however, lacked consistency across measures. Scopolamine remains a promising agent and additional research required to further understand its effects.
Background: In rodents, context specificity of Pavlovian extinction is attenuated by manipulations that impair hippocampal function, including systemic administration of scopolamine, a muscarinic-cholinergic receptor antagonist. Context renewal translates into return of fear following exposure therapy to feared situations. We evaluated the effectiveness of scopolamine for attenuating context renewal of phobic fear in humans. Methods: A total of 60 participants (35 female, 22 male, 1 transgender, 2 undeclared) with social anxiety disorder and fear of public speaking were randomized to placebo, 0.5 mg scopolamine, or 0.6 mg scopolamine. They completed seven exposure sessions in an exposure context and subsequently tested in the exposure context (extinction retest) versus a different context (context renewal test), which were counterbalanced. Testing 1 month later occurred in the exposure context (long-term extinction retest). Fear measures included skin conductance and self-reported distress during speeches. Hippocampus-dependent cognitive tasks were completed as well. Results: Scopolamine augmented extinction across exposure sessions on skin conductance response and skin conductance level. Lower skin conductance response at context renewal in scopolamine groups relative to the placebo group was constrained to simple effects and complicated by unexpected outcomes within placebo and on self-reported fear. Scopolamine led to lower skin conductance response at long-term extinction retest. Scopolamine impaired performance on a cognitive task of hippocampal function. Conclusions: Noninvasive and well-tolerated scopolamine impaired hippocampal processes and augmented extinction during exposure. Drug-free effects persisted 1 month later. Findings at context renewal were limited and suggestive only. Further investigation is warranted with varying scopolamine dosages.
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Treatment of specific fears and phobias is sometimes followed by a return of fear. Work with rats has provided evidence that a greater return of fear occurs when a conditioned stimulus extinguished in 1 context is later presented in a different context than if presented in the same context in which it was originally extinguished. In the present study, 36 human participants who were highly afraid of spiders received 1 session of exposure therapy (with participant modeling) and were then tested for return of fear 1 week later in either the same or a different context. It was hypothesized that there would be a greater return of fear in those participants treated and followed up in different contexts than in those treated and followed up in the same context. Participants tested in a novel context at follow-up showed a greater return of fear than participants tested in the same context. Limitations and areas for future study are discussed.
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Impulsivity has been interpreted as a stable mediator of rate of change in arousal states. To test this hypothesis, 129 Ss differing in impulsivity were given placebo or caffeine at 9:00 a.m. or 7:30 p.m. Recognition memory was tested for the last 20 items from 2 lists of 24 items and 2 lists of 80 items. Scores from this paradigm reflect sustained attention and are thus sensitive to changes in arousal. A 4-way interaction among impulsivity, time of day, drug, and prior stimuli (p < .05) indicated that for those given placebo, recognition memory for long and late lists was poorer the higher the impulsivity in the morning; this pattern reversed in the evening. Caffeine reduced recognition errors. These results indicate that impulsivity is not a stable predictor of rate of change in arousal states. Instead, susceptibility to attentional lapses is mediated by impulsivity-related phase differences in diurnal arousal rhythms.
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Four experiments with rats were run to investigate whether fear extinction conducted under the influence of a benzodiazepine transfers to the undrugged state. Fear was conditioned by pairing an experimental chamber with footshock and was assessed by observing freezing, a characteristic response of the rat to stimuli associated with shock. In Experiment 1, extinction of the chamber cues under chlordiazepoxide (librium) or diazepam (valium) was compared with extinction under a placebo; both drugs interfered with extinction in a dose-dependent manner as indicated by freezing during an undrugged test. Further results with chlordiazepoxide suggested that the effect depended on the drug’s specific combination with extinction and that it occurred even though the extinction procedure otherwise eliminated fear completely (Experiment 2). Repeated preexposure to the drug, and the development of partial tolerance to its sedative effects, did not weaken the interference effect (Experiment 3). Other evidence suggested that the drug signaled or retrieved extinction instead of disrupting learning or consolidation (Experiment 4). The results are consistent with research suggesting that extinguished fear can be “renewed” if the exteroceptive contextual stimuli are changed after extinction. Extinction combined with either unique exteroceptive or interoceptive cues may be specific to its context.
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Beliefs held by spider phobics about a confrontation with a spider are investigated. Study 1 explores the content of thoughts and images which spider phobics (N = 44) report to have during a confrontation with a spider and investigates the frequency and strength of the subjective belief in the idea. Spider phobics appear to have an abundance of negative, irrational ideas about the spider and about their own reactions during a confrontation with a spider. A one-session therapistassisted exposure therapy strongly attenuates these beliefs. Study 2 investigates the psychometric properties of the Spider Phobia Beliefs Questionnaire (SBQ), which measures the strength of belief of a large number of ideas derived from Study 1, in a second sample of spider phobics (N = 112). Factor analysis revealed 5 spider-related factors: harm, hunter and prey, unpredictability, territory, and multiplication; and 4 self-related factors: panic, paralysis, incubation, and unrestrained behavior. These factors have good internal consistency and reasonable test-retest reliability. The SBQ discriminates strongly between spider phobics and normals (N = 33) and has good concurrent validity as indicated by positive associations with other indices of spider phobia. It appears that spider phobics have a lot of misconceptions about spiders, e.g., that spiders attack them, take revenge, or are incalculable and about their own reactions about a confrontation with a spider, e.g., they expect to have a heart attack, to die of fear, or to exacerbate their fear. Most self-related ideas resemble those held by panic patients. Both spider-related and self-related ideas can be corrected by a one-session treatment.
Four conditioned suppression experiments examined the influence of contextual stimuli on the rat's fear of an extinguished conditioned stimulus (CS). When rats received pairings of a CS with shock in one context and then extinction of the CS in another context, fear of the CS was renewed when the CS was returned to and tested in the original context (Experiments 1 and 3). No such renewal was obtained when the CS was tested in a second context after extinction had occurred in the conditioning context (Experiment 4). In Experiment 2, shocks presented following extinction reinstated fear of the CS, but only if they were presented in the context in which the CS was tested. In each experiment, the associative properties of the contexts were independently assessed. Contextual excitation was assessed primarily with context-preference tests in which the rats chose to sit in either the target context or an adjoining side compartment. Contextual inhibition was assessed with summation tests. Although reinstatement was correlated with demonstrable contextual excitation present during testing, the renewal effect was not. Moreover, there was no evidence that contextual inhibition developed during extinction. The results suggest that fear of an extinguished CS can be affected by the excitatory strength of the context but that independently demonstrable contextual excitation or inhibition is not necessary for contexts to control that fear.
Theories of learning and of memory have been artificially separated for many years. In this article it is argued that the separation should be abandoned. Remembering and forgetting play an important role in simple conditioning experiments. For example, conditioned performance can readily recover after extinction because extinction is susceptible to forgetting. Memory itself involves the kind of associative learning that conditioning experiments are designed to investigate (e.g., conditioning experiments provide insight into the mechanisms of memory retrieval). Learning, remembering, and forgetting all occur within the same biological context; their adaptive functions are therefore intertwined. Taken together, they shed light on some of the mechanisms of clinical relapse. Conditioning theory enriches, and is enriched by, the field of memory as well as other fields of behavioral science.
This paper deals with questionnaires tapping fears of snakes, spiders, mutilation, and public speaking. Psychometric description of the scales across several samples indicated consistent distribution characteristics. In addition, consistently high reliability estimates were obtained; available results on test-retest reliability and validity were also encouraging. Correlations of these tests with one another and with general measures of anxiety indicated little shared variance. Inclusion of these scales in fear assessment procedures is suggested to promote standardization of evaluation and comparability of results across samples and laboratories.