![Mood change scores on the composed-anxious scale of the Profile of Mood States were computed by subtracting the mood ratings after the first YIPS conversation from the mood ratings of the postrelaxation baseline. High and low emotion-oriented coping scores were set to one standard deviation above and below the mean, respectively. Error bars represent 1 standard error in either direction. Relative to placebo, female participants with high emotion-oriented coping scores reported less anxiety in response to the YIPS following oxytocin administration [b ϭ 4.487, t (91) ϭ 2.09, p Ͻ .05]. Neither female participants with low emotion- oriented coping scores nor male participants exhibited this anxiolytic effect.](https://www.researchgate.net/profile/Christopher-Cardoso-2/publication/51711232/figure/fig1/AS:305968677179399@1449960025868/Mood-change-scores-on-the-composed-anxious-scale-of-the-Profile-of-Mood-States-were_Q320.jpg)
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Coping Style Moderates the Effect of Intranasal Oxytocin on the Mood
Response to Interpersonal Stress
Christopher Cardoso and Anne-Marie Linnen
Concordia University
Ridha Joober
McGill University
Mark A. Ellenbogen
Concordia University
Recent evidence suggests self-administration of intranasal oxytocin may facilitate social interaction
by attenuating the stress response to interpersonal conflict. Currently, no published research has
documented whether intraindividual factors moderate the effect of intranasal oxytocin on the
emotional response to stress. The aim of the present study was to determine whether coping style
moderates the effect of intranasal oxytocin on mood in response to an interpersonal stressor in
healthy men and women. In a double-blind placebo-controlled experiment, 100 undergraduate
students (50 women) participated in the Yale Interpersonal Stressor (YIPS: Stroud, Tanofsky–Kraff,
Wilfley, & Salovey, 2000), a live social rejection paradigm. Prior to the YIPS, participants were
randomly assigned to self-administer either intranasal oxytocin (24 IU) or a placebo. Coping was
measured using the Coping Inventory for Stressful Situations. Multiple regression analyses predict-
ing stress-related changes in anxiety revealed a significant Drug ⫻Emotion-oriented coping ⫻Sex
interaction [pr
2
⫽.06, b ⫽6.074, t(91) ⫽⫺2.526, p⫽.014]. Follow-up analyses using simple
slopes revealed self-administration of intranasal oxytocin reduced anxiety in response to the YIPS
relative to the placebo in women high in emotion-oriented coping [b ⫽4.487, t(91) ⫽2.09, p⬍.05],
but not in women low in emotion-oriented coping, or men. The results suggest that intraindividual
factors modulate the effect of intranasal oxytocin on the affective response to stress. Intranasal
oxytocin appears to be particularly beneficial to women who endorse high levels of emotion-oriented
coping, who may be vulnerable to the negative impact of stress.
Keywords: intranasal oxytocin, anxiety, social rejection, emotion-oriented coping
Chronic interpersonal stress, which refers to long-term distur-
bances and ongoing difficulties in social relations such as marital
conflict, is associated with the development of a host of physical
and emotional problems, including cardiovascular disease (Orth–
Gomer Wamala, & Horsten,, 2000) and depression (Eberhart &
Hammen, 2006; Hammen, Shih, & Brennan, 2004). It has also
been reported as a proximal marker of vulnerability for affective
disorders in high-risk populations, such as offspring of parents
with bipolar disorder (Ostiguy et al., 2009). Although the effect of
interpersonal stress on health is well established, our understand-
ing of the mechanisms underlying this relation requires greater
emphasis in the literature. Oxytocin, a neuropeptide germane to
affiliative behavior, may be implicated in the regulation of inter-
personal stress (Taylor et al., 2000). Oxytocin is stored in the
paraventricular nucleus of the hypothalamus, and is released both
centrally in the limbic system, and peripherally in the blood stream
through the posterior pituitary gland (Gimpl & Fahrenholz, 2001).
Although oxytocin is best known for its role in reproductive
functions, studies indicate that oxytocin regulates different social
behaviors including pair bonding and social recognition in animals
(Carter, 1998; Panksepp, Nelson, & Bekkedal, 1997). Consistent
with these data, human studies using intranasal peptide adminis-
This article was published Online First October 10, 2011.
Christopher Cardoso, Anne-Marie Linnen, and Mark A. Ellenbogen,
Centre for Research in Human Development, Concordia University, Mon-
treal, Que´bec, Canada; Ridha Joober, Douglas Hospital Research Centre,
McGill University, Montreal, Que´bec, Canada.
This research was supported by grants to Dr. Ellenbogen from the
Canadian Institutes of Health Research and the Canada Research Chair
program (supported by the Social Sciences and Humanities Research
Council of Canada; SSHRC). Christopher Cardoso is supported by a
scholarship from the Natural Sciences and Engineering Research Council
of Canada. Dr. Ellenbogen is currently supported by a Canada Research
Chair appointment from SSHRC.
Christopher Cardoso developed the hypotheses, conducted the statistical
analysis, and wrote the first draft of the manuscript. Anne-Marie Linnen
and Mark A. Ellenbogen designed the study, wrote the study protocol, and
extensively edited and revised the final version of the manuscript. Ridha
Joober supervised all procedures relating to the use of oxytocin. All authors
contributed to and have approved the final manuscript.
All authors on this article declare that they have no biomedical financial
interests or potential conflicts of interest.
Correspondence concerning this article should be addressed to Mark
A. Ellenbogen, Centre for Research in Human Development, Concordia
University, 7141 Sherbrooke Street West, Montre´al, Que´bec H4B 1R6.
E-mail: mark.ellenbogen@concordia.ca
Experimental and Clinical Psychopharmacology © 2011 American Psychological Association
2012, Vol. 20, No. 2, 84–91 1064-1297/11/$12.00 DOI: 10.1037/a0025763
84
tration (Born et al., 2002) indicate that oxytocin promotes positive
communication in the context of a laboratory stressor in which
couples discuss a point of contention in their relationship (Ditzen
et al., 2009). Furthermore, central oxytocin attenuated cortisol
following a public speaking laboratory stressor in humans (Hei-
nrichs, Baumgartner, Kirschbaum, & Ehlert, 2003), which sug-
gests oxytocin may serve to ameliorate the negative impact of
social stress.
Psychological factors also moderate the impact of stress expo-
sure. It is well established that a person’s response to difficult
circumstances varies greatly depending on contextual and intrain-
dividual factors (Lazarus & Folkman, 1984). An active form of
coping with stress, which focuses on alleviating the stressful
circumstance, is typically associated with stress attenuation and
effective emotion regulation (Feder, Nestler, & Charney, 2009;
Lazarus & Folkman, 1984). On the other hand, coping styles aimed
at regulating emotions through negative self-talk and emotional
expression are associated with outcomes such as increased depres-
sive symptoms and anxiety (Baschnagel, Gudmundsdottir, Hawk,
& Beck, 2009; Lazarus & Folkman, 1984; Ravindran, Griffiths,
Waddell, & Anisman, 1995; Veenstra et al., 2007).
Emphasis on emotion-oriented coping strategies is positively
correlated with higher levels of distress and increased rumination
in response to stress (Clarke & Goosen, 2009; Lazarus & Folkman,
1984). Individuals who endorse higher levels of emotion-oriented
coping strategies also report less perceived control over stress
(Folkman & Moskowitz, 2004). Moreover, emotion-oriented cop-
ing is elevated in individuals suffering from major depression
relative to nondepressed control participants (Ravindran, Methe-
son, Griffiths, Merali, & Anisman, 2002), and tends to increase
during depressive episodes (Ravindran et al., 1995). Because de-
pression is associated with higher levels of interpersonal stress that
is dependent, in part, on the person’s own behavior (Hammen,
2005), it is possible that this coping style serves to maintain and/or
exacerbate interpersonal stress.
The Yale Interpersonal Stressor (YIPS), a stress induction in
which two confederates socially exclude a participant from a
conversation during a “discussion group,” is considered to be a
useful laboratory test of interpersonal stress reactivity (Stroud et
al., 2000). The original studies published by Stroud and colleagues
(Stroud et al., 2000; Stroud, Salovey, & Epel, 2002) reported an
affective response to the YIPS in male and female participants, and
a cortisol response to the YIPS in females. We have recently
examined the effect of intranasal oxytocin on the mood and cor-
tisol response to the YIPS in 100 university students. Relative to
baseline, the YIPS increased negative mood in the full sample,
with female participants reporting more negative mood change
than male participants (Linnen et al., in press). Although oxytocin
attenuated cortisol levels during the YIPS relative to a placebo
administration, we did not detect any beneficial effects of oxytocin
on the mood response to the YIPS (Linnen et al., in press). These
findings are consistent with previous research examining the effect
of oxytocin on mood (Alvares, Hickie, & Guastella, 2010; Kirsch
et al., 2005; Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005).
The effect of intranasal oxytocin on mood may depend on
intraindividual factors. Although previous studies have reported no
effect of intranasal oxytocin on mood (Alvares et al., 2010; Kirsch
et al., 2005; Kosfeld et al., 2005), interactions were not investi-
gated. Whereas researchers have attempted to delineate individual
variation in physiological activity under the influence of intranasal
oxytocin (Meinlschmidt & Heim, 2007; Norman et al., 2011;
Quirin, Kuhl, & Dusing, 2011), the aim of the present study was to
determine whether the effect of intranasal oxytocin on mood in
response to interpersonal stress, as described above, is moderated
by coping style during a live social rejection paradigm with high
ecological validity.
To date, most researchers have investigated the effect of intra-
nasal oxytocin on behavior in response to social challenge mostly
among men, and not women, with two notable exceptions that used
mixed samples (Alvares et al., 2010; Ditzen et al., 2009). Thus,
research on central oxytocin in women is less available than it is
for men. Oxytocin is modulated by estrogen in the central nervous
system (Gimple & Farenholz, 2001), and greater levels of estrogen
in women relative to men may differentially influence the putative
effects of intranasal oxytocin on mood. Furthermore, women gen-
erally report greater levels of interpersonal stress than men (Ham-
men, 2005), which may be in part dependent on a greater emphasis
on emotion-oriented coping strategies relative to men (Cyranowski
et al., 2000; Tamres, Janicki, & Helgeson, 2002). Although it is too
early to suggest a definitive relationship between coping, sex, and
the effect of oxytocin on mood, we contend this relationship
warrants investigation.
In the current study, we recruited an equal number of men and
women to examine sex differences in the emotional response to
stress following the administration of intranasal oxytocin. To ad-
dress the questions raised previously, the present study draws on
data from our previous study of the effects of oxytocin on the
mood and cortisol response to the YIPS (Linnen et al., in press)
described above. We hypothesized that intranasal oxytocin would
elicit a larger reduction in anxiety among individuals high in
emotion-oriented coping than individuals lower in emotion-
oriented coping. In short, individuals who endorse high levels of
emotion-oriented coping are expected to benefit the most from the
documented anxiolytic effects of oxytocin (Ditzen et al., 2009;
Heinrichs et al., 2003). Furthermore, because women have ele-
vated estrogen levels and report more emotion-focused coping
(Tamres et al., 2002) and interpersonal stress (Hammen, 2005)
than men, we will examine possible sex differences in the rela-
tionship between oxytocin, coping, and the mood response to the
YIPS.
Method
Participants
One hundred undergraduate students (50 males/50 females),
between the ages of 18 and 35 years, were recruited through
advertisements placed in local universities. Exclusion criteria in-
cluded current medication use, presence of a medical illness or of
a current or past mental disorder, recreational drug use, smoking,
pregnancy, and poor English language fluency. One participant
dropped out of the study before completing the questionnaires at
the end of the study, and was therefore omitted from the analyses.
The mean age of male and female participants was 21.6 ⫾3.1 and
22.4 ⫾3.7 years, respectively. Forty-eight participants were ad-
ministered oxytocin (24 males/24females) and 51 participants
were administered the placebo (25 males/26 females).
85
COPING, OXYTOCIN, AND INTERPERSONAL STRESS
Measures
The Profile of Mood States: Bipolar Form (POMS: McNair,
Lorr, & Heuchert, 1982), a 72-item inventory, was used to measure
current affective state. This questionnaire assesses six bipolar
subjective mood states composed of 12 adjectives rated on a scale
from 0 (not like me)to3(very much like me): composed–anxious,
elated– depressed, agreeable–hostile, sure– unsure, clear–
confused, and energetic–tired. The POMS shows good internal
consistency, test–retest reliability, and convergent validity with
other scales (McNair et al., 1982). In this study, the composed–
anxiety scale (␣⫽.83) was the main dependent variable of our
analysis because oxytocin has been primarily investigated in the
literature with respect to anxiolytic effects (Carter, 1998). We ran
secondary analyses on the elated– depressed scale (␣⫽.86),
agreeable– hostile scale (␣⫽.86), and the sure– unsure scale (␣⫽
.81) of the POMS because these emotions are theoretically relevant
to social rejection. The clear– confused and energetic–tired scales
of the POMS were omitted from the analyses entirely because no
published research has documented evidence of an effect of central
oxytocin on these mood dimensions, and they are less relevant to
social rejection than the aforementioned scales.
The Coping Inventory for Stressful Situations (CISS: Endler &
Parker, 1990), a 48-item inventory, was used to measure coping
style in response to stressful situations. Participants are instructed
to indicate how much they engage in the types of activities listed
in the questionnaire when they encounter a difficult, stressful, or
upsetting situation. Subscales of this inventory include task-
oriented, emotion-oriented, and avoidance-oriented coping. The
CISS has good internal consistency and reliability (task-oriented:
␣⫽.90, r⫽.73; emotion-oriented: ␣⫽.87, r⫽.71) and
convergent validity with other scales (Endler & Parker, 1990;
McWilliams, Cox, & Enns, 2003). In the current sample, items on
the emotion-oriented coping scale (␣⫽.89) of the CISS include
“Feel anxious about not being able to cope” and “Blame myself for
being too emotional about the situation.” Items on the task-
oriented coping scale (␣⫽.74) include “Work to understand the
situation” and “Analyze the problem before reacting.” These scales
are directly relevant to the coping strategies employed during
stressful social interactions, and are thus particularly relevant to
the present study. Avoidance-oriented coping was less relevant to
the present study because participants were required to participate
in the live social rejection paradigm and could not employ avoid-
ance strategies. For this reason, avoidance coping was excluded
from the data analyses.
Yale Interpersonal Stressor
The YIPS (Stroud et al., 2000) involves two interactions be-
tween a participant and two same-sexed confederates posing as
students in a discussion group for an experiment on communica-
tion skills, in which the participant is made to feel excluded and
isolated. Participants engaged in two separate conversations lasting
10 min each while being video recorded and observed through a
one-way mirror. During the first 2 min, confederates engaged in
polite conversation with the participant. Between minutes 2 and 4,
confederates began to express interest in one another while re-
maining relatively neutral to the participant. As the conversation
progresses over the next 6 min, the confederates increasingly
exclude the participant from the conversation, both verbally and
nonverbally. For specific information concerning this protocol, see
the original manuscript published by Stroud and colleagues (2000).
Confederates underwent three 2-hr training sessions prior to the
study. They received feedback from the study coordinators after
every experimental session to prevent behavior change over the
course of the experiment and to decrease inconsistencies between
confederates.
Procedure
Students were recruited to participate in a study investigating
the effects of oxytocin on communication skills. Upon arrival at
the laboratory, participants gave informed consent and completed
a medical history questionnaire to screen out participants with
medical and psychiatric disorders, those who were pregnant, and
those who were taking medication. Next, participants completed
the POMS (#1), and were randomly assigned to receive either an
intranasal 24-IU dose of oxytocin (Syntocinon, Novartis, Switzer-
land) or placebo (saline). The experimenter and participant were
blind to the substance being administered. Participants received
instruction on administration of the drug, then self-administered
the nasal spray three times in each nostril, and began a 50-min
baseline relaxation phase in which they read magazines or watched
neutral documentaries. After the baseline relaxation phase, partic-
ipants completed another POMS (#2) and were brought into a
common room where one confederate was already seated. The
experimenter then guided the second confederate into the common
room.
Next, the experimenter explained the task to the group and
informed them that their conversations would be viewed through a
one-way mirror and recorded on video. Participants were informed
that they would evaluate one another at the end of each conver-
sation, in addition to being evaluated by the experimenter. The
experimenter then turned on the camera and left the room, upon
which the conversation began.
After the first conversation was over, participants returned to
their individual rooms to fill out the POMS (#3). Once completed,
the participant took part in a second YIPS conversation, followed
by the final POMS (#4). At the completion of the YIPS, partici-
pants completed a battery of questionnaires, which included the
CISS. Participants were then fully debriefed and remunerated $50
dollars for their participation. All participants provided written
informed consent and the study was approved by the Concordia
University Human Research Ethics Committee.
Statistical Analyses
Missing scores consisted of less than 0.1% of sample data and
were randomly distributed. These data points were replaced by the
participant’s mean on each scale. An increase in score on the
POMS is associated with an improvement in mood, whereas a
decrease in score is associated with a worsening of mood. Partic-
ipants’ POMS ratings of anxiety in the full sample during the study
were 27.03 ⫾6.09 at baseline, 29.49 ⫾4.76 after the 50-min
relaxation phase, 25.02 ⫾7.21 after the first YIPS conversation,
and 25.04 ⫾7.42 after the second YIPS conversation. Mood
change scores were computed by subtracting POMS scores after
the first YIPS conversation (POMS #3) from scores after the
86 CARDOSO, LINNEN, JOOBER, AND ELLENBOGEN
relaxation period (POMS #2), which was the largest difference
between time points in the study with the shortest temporal con-
tiguity. We did not assess the difference between two POMS
scores that were not measured sequentially. Affect changes rela-
tively quickly, and because mood scores on the POMS reflect
current affective state, short temporal contiguity is critical to the
interpretation of the difference between sequential POMS scores.
Furthermore, scores on POMS #3 were strongly related to scores
on POMS #4 (r⫽.84), and because the mean difference between
these two time points was .02 ⫾4.25 (less than one-tenth of 1
point on the POMS mood scale), we considered the difference
between these time points negligible, and omitted POMS #4 from
the analyses. Descriptive statistics for relevant time points can be
found in Table 1.
A multiple regression model predicting mood change on the
composed–anxiety scale of the POMS was conducted, with coping
scores (emotion-oriented), drug (placebo, oxytocin), sex, and their
interactions as predictor variables. Drug condition was dummy
coded 0 (placebo) and 1 (oxytocin). Sex was dummy coded 0
(males) and 1 (females). Scores on the emotion-oriented coping
scale were transformed into Z scores before being entered into the
regression model. Product terms were residualized relative to
lower-order terms to circumvent issues related to multicollinearity,
and to allow for the interpretation of main effects in each model.
Significant interactions were followed up with tests of simple
slopes, which assess the magnitude of different effects that con-
tribute to an interaction (Aiken & West, 1991). Data were analyzed
using the Statistical Package for the Social Sciences version 16.0.
All ␣values were set to 0.05.
Results
Ratings of Mood and Coping Style
Participants’ mood ratings following the relaxation period and
after the first YIPS conversation are presented in Table 1. For
measures of coping, an independent groups ttest revealed that men
(mean ⫾SD; 39.9 ⫾11.0) were less likely to endorse emotion-
oriented coping than females [44.3 ⫾10.32; t(97) ⫽2.03, p⬍
.05]. There were no significant sex differences on the task-
oriented coping scale [males: 61.3 ⫾9.1; females: 61.8 ⫾8.9;
t(97) ⫽0.253, p⬎.05]. As expected, emotion-oriented coping,
but not task-oriented coping, was modestly associated with
baseline levels of anxiety on the POMS [r(99) ⫽⫺.21, p⫽
.037]. Furthermore, there was no main effect of drug condition
on baseline levels of anxiety on the POMS, t(97) ⫽.663, p⬎
.05.
Does Coping Style Moderate the Relation Between
Oxytocin and the Anxiety Response to Interpersonal
Stress?
A multiple regression analysis was conducted on POMS
composed–anxiety change scores. The following predictors were
simultaneously entered into a regression model: drug condition,
sex, emotion-oriented coping, the Drug ⫻Sex interaction, the
Drug ⫻Emotion-oriented coping interaction, the Sex ⫻Emotion-
oriented coping interaction, and the Drug ⫻Sex ⫻Emotion-
oriented coping interaction. This model was statistically significant
[⌬R
2
⫽.144, F(7, 91) ⫽2.185, p⫽.043]. Self-reported data on
menstrual cycle phase collected from females was entered in the
aforementioned regression model as a covariate, and as an inter-
action term with drug condition. However, because these predic-
tors did not substantively contribute to this model, they were
subsequently removed. Sex was a statistically significant predictor
of composed-anxiety change scores [pr
2
⫽.059, b ⫽⫺2.925,
t(91) ⫽⫺2.501, p⫽.013]. Furthermore, the interaction between
drug, sex, and emotion-oriented coping was a statistically signif-
icant predictor of composed-anxiety change scores [pr
2
⫽.06, b ⫽
6.074, t(91) ⫽⫺2.526, p⫽.014]. The remaining predictors in this
model were not statistically significant. A visual inspection of the
regression model revealed no substantive suppression effects.
Simple slope analyses, according to Aiken and West (1991),
were conducted to assess the effect of drug on anxiety levels
among males and females low (1 standard deviation below the
mean) and high (1 standard deviation above the mean) in
emotion-oriented coping, which is illustrated in Figure 1. Sim-
ple slope analyses revealed that the slope for females with low
Table 1
Mood Scores on the POMS Scales After the 50-Minute Relaxation Period and Following the First YIPS Conversation
Variable
After 50-min
relaxation
Post 1st YIPS
conversation 95% CI
Glass’ ⌬M SD M SD LL UL
Females
Composed–Anxious 30.80 4.96 24.10 8.16 4.19 7.77 1.21
Elated–Depressed 24.34 5.43 20.16 7.06 2.69 5.67 0.77
Agreeable–Hostile 29.42 3.93 24.02 7.71 3.61 7.19 1.37
Sure–Unsure 22.00 5.26 20.18 7.03 0.50 3.14 0.35
Males
Composed–Anxious 28.90 4.53 26.00 6.01 1.45 4.35 0.64
Elated–Depressed 24.94 5.09 22.92 5.72 0.75 3.29 0.40
Agreeable–Hostile 28.49 4.54 25.61 5.33 1.42 4.34 0.63
Sure–Unsure 24.57 4.60 23.65 5.71 ⫺0.20 2.04 0.20
Note. LL ⫽lower limit; UL ⫽upper limit.Glass’ ⌬is a measure of effect size, and the standard deviation of the baseline mood scores were used as the
denominator for these equations.
87
COPING, OXYTOCIN, AND INTERPERSONAL STRESS
emotion-oriented coping across drug condition was not statis-
tically significant [b ⫽⫺3.634, t(91) ⫽⫺1.37, p⬎.05]. That
is, the administration of oxytocin had no statistically significant
effect on anxiety in females who were low in emotion-oriented
coping. In contrast, the slope for females with high emotion-
oriented coping across drug condition was statistically signifi-
cant [b ⫽4.487, t(91) ⫽2.09, p⫽.039]. That is, the admin-
istration of oxytocin was associated with a reduction in anxiety
relative to placebo in females high in emotion-oriented coping.
The slopes for males with low emotion-oriented coping [b ⫽
1.265, t(91) ⫽0.61, p⬎.05] and high emotion-oriented coping
[b ⫽⫺2.764, t(91) ⫽⫺1.06, p⬎.05] were not statistically
significant across drug condition.
Does Coping Style Moderate the Relation Between
Oxytocin and Other Indices of Mood Change in
Response to Interpersonal Stress?
As a set of secondary analyses, a multiple regression analysis
was conducted on the change scores for the remaining retained
scales of the POMS. The same seven predictors in the previous
analysis were included in these regression models predicting mood
change scores for the elated– depressed [⌬R
2
⫽.128, F(7, 91) ⫽
1.913, p⬎.05], agreeable– hostile [⌬R
2
⫽.134, F(7, 91) ⫽2.017,
p⬎.05], and the sure– unsure [⌬R
2
⫽.108, F(7, 91) ⫽1.581, p⬎
.05] scales of the POMS. As described above, self-reported data on
menstrual cycle phase did not substantively contribute to these
models, and was therefore dropped as a predictor. The results of
these regression models did not reach statistical significance, and
were not probed further.
The Effects Oxytocin on Participants’ Ratings of
Coping Style
Because the CISS was administered at the end of the study, after
participants were administered oxytocin or the placebo, secondary
analyses were conducted to examine if there were group differ-
ences in reported scores on the emotion-oriented and task-oriented
coping scales. An independent groups ttest revealed that partici-
pants in the oxytocin condition had significantly higher task-
oriented coping scores (63.8 ⫾8.3) than participants in the pla-
cebo condition [59.4 ⫾9.1; t(97) ⫽2.50, p⬍.05]. This result was
similar in across males [59.4 ⫾9.2] and females [59.4 ⫾9.1] in
the placebo condition relative to males [63.25 ⫾8.7] and females
[64.3 ⫾8.2] in the oxytocin condition. No statistically significant
differences were observed on the emotion-oriented coping scale
[placebo: 42.0 ⫾10.8; oxytocin: 42.3 ⫾11.0; t(97) ⫽0.17, p⬎
.05]. This result did not vary substantively across sex. These data,
unexpectedly, indicate that the administration of oxytocin may
have influenced the self-report of task-oriented, but not emotion-
oriented, coping in the full sample.
To verify whether task-oriented scores on the CISS were in
fact influenced by oxytocin, we assessed whether group differ-
ences during the study were present at a later assessment of
coping, under no drug administration. Seventy-two partici-
pants—33 from the original placebo condition and 39 from the
oxytocin condition—agreed to complete the CISS 374 ⫾57
days following the experiment. Mean coping scores on the
task-oriented scale were 56.12 ⫾8.63 and 59.23 ⫾8.01 among
participants in the placebo and drug condition, respectively.
This group difference was not statistically significant [t(70) ⫽
1.58, p⬎.05], indicating that the group difference on task-
oriented coping scores in our original analysis was absent when
assessed approximately one year later. As expected, there was
no group difference in emotion-oriented coping at follow-up
[placebo group: 38.36 ⫾9.24; oxytocin group: 40.56 ⫾11.91;
t(70) ⫽.874, p⬎.05], consistent with the first assessment.
These findings suggest that the group difference in task-
oriented coping were elicited from the experimental drug ma-
nipulation. In contrast, no evidence of a similar effect of drug
manipulation on emotion-oriented coping scores was observed,
Figure 1. Mood change scores on the composed-anxious scale of the Profile of Mood States were computed
by subtracting the mood ratings after the first YIPS conversation from the mood ratings of the postrelaxation
baseline. High and low emotion-oriented coping scores were set to one standard deviation above and below the
mean, respectively. Error bars represent 1 standard error in either direction. Relative to placebo, female
participants with high emotion-oriented coping scores reported less anxiety in response to the YIPS following
oxytocin administration [b ⫽4.487, t(91) ⫽2.09, p⬍.05]. Neither female participants with low emotion-
oriented coping scores nor male participants exhibited this anxiolytic effect.
88 CARDOSO, LINNEN, JOOBER, AND ELLENBOGEN
indicating that participants’ ratings of emotion-oriented coping
were independent of the drug administration. Moreover, we
calculated test–retest reliability of emotion-oriented coping in a
subset of our sample over the span of a year (n⫽72). Reli-
ability (r(71) ⫽.65, p⬍.001) was comparable to that reported
by Endler and Parker in college students over 4 weeks with a
much larger sample (r⫽.71; Endler & Parker, 1990), suggest-
ing that this measure assessed stable individual differences in
coping strategies in this study. Taken together, these data
indicate that emotion-oriented coping was a suitable predictor
in the analyses described above, independent of drug adminis-
tration.
Discussion
The aim of the present study was to examine whether coping
style moderated the effect of intranasal oxytocin on the anxiety
response to the YIPS. We hypothesized that oxytocin would have
an anxiolytic effect in participants who endorsed high levels of
emotion-oriented coping—a style of responding to stress that is
associated with psychopathology and poor interpersonal function-
ing (Ravindran et al., 1995; Ravindran et al., 2002). The results of
the present study are consistent, in part, with this contention.
Women who endorsed high levels of emotion-oriented coping
experienced less anxiety in response to the YIPS after inhaling a
24-IU dose of oxytocin than women high in emotion-oriented
coping who inhaled the placebo. This result was not observed in
men. An additional consideration is that men were less responsive
to the YIPS, and the paradigm used in the current study may be
more effective for identifying underlying stress-regulation mech-
anisms in women than in men. This contention is consistent with
the literature (Stroud et al., 2000; Stroud et al., 2002).
Participants who received intranasal oxytocin reported higher
scores on the task-oriented coping scale of the CISS than partici-
pants in the placebo group. This finding, albeit unexpected, sug-
gests that intranasal oxytocin altered participants’ perception of
their task-oriented coping ability. The effect of oxytocin on task-
oriented coping is consistent with a recent report of increased
self-perceptions of attachment security among insecurely attached
adults following the administration of oxytocin (Buchheim et al.,
2009). Oxytocin may promote social affiliation by increasing
participants’ perceptions of attachment security and solution-
oriented coping skills, which are considered socially desirable
(Endler & Parker, 1990).
Since the emotion-oriented coping subscale of the CISS was
used as a predictor in our analyses, it is important to note that,
unlike task-oriented coping, we found no evidence that it was
affected by the drug manipulation. No effect of drug condition on
emotion-oriented coping scores was found during the experiment
or at a 1-year follow-up. Despite the exposure to a laboratory
stressor and drug administration, the test–retest reliability of
emotion-oriented coping scores in our sample was similar to those
reported by the authors of the CISS (Endler & Parker, 1990). Thus,
the emotion-oriented coping scores used in the study appear to be
assessing general coping style in participants, which is what par-
ticipants are instructed to do when completing the inventory,
independent of drug administration and other state-related factors
during the experiment.
The finding that women who report higher levels of emotion-
oriented coping benefit from oxytocin raises the possibility that
variations in the oxytocinergic system may underlie a vulnerability
to psychosocial dysfunction. It is of note that depressed samples
endorse greater levels of emotion-oriented coping than nonde-
pressed samples (Ravindran et al., 2002). Although the literature
on depression is mixed (Cyranowski et al., 2008), with some
studies reporting evidence of elevated oxytocinergic function in
depression (Meynen, Unmehopa, Hofman, Swaab, & Hoogendijk,
2007; Parker et al., 2010; Purba, Hoogendijk, Hofman, & Swaab,
1996), a number of studies have reported low plasma oxytocin
levels in persons with major depression as compared with controls
(Frash, Zetzsche, Steiger, & Jirikowski, 1995; Ozsoy, Esel, &
Kula, 2009; Scantamburlo et al., 2007). Moreover, exposure to
childhood abuse or neglect, linked to the development of depres-
sion and other mental disorders, was associated with lower levels
of oxytocin in cerebrospinal fluid in women (Heim et al., 2009).
Thus, an increased sensitivity to the administration of oxytocin in
women with a high emotion-oriented coping style may highlight a
putative vulnerability in the oxytocinergic system, perhaps asso-
ciated with an increased risk for depression. A recent study is
consistent with this view. The administration of intranasal oxyto-
cin improved social cognition in participants reporting poor social
competencies, but had no effect in those reporting normal social
abilities (Bartz et al., 2010). Clearly, more research is needed to
support these speculations.
This study has several limitations. First, we cannot conclusively
rule out an effect on menstrual cycle phase on the reported find-
ings. It is noteworthy that self-reported menstrual cycle phase was
not a significant predictor in our model, considering there is
evidence to suggest oxytocin receptor density may be upregulated
by estrogen in the central nervous system (Gimple & Farenholz,
2001). Had we collected blood samples to assay estrogen—a
method far more precise than self-reported menstrual informa-
tion— our model may have been more sensitive to this possible
effect. Second, the placebo nasal spray used in the control condi-
tion contained a saline solution without the inactive compounds
present in the oxytocin solution. Thus, it is possible that some of
the findings observed in the present study could be due to the
effects of a nonactive compound administered with oxytocin.
Third, although emotion-oriented coping is believed to be valid
indicator of coping style, which increases a person’s susceptibility
to stress (Baschnagel, Gudmundsdottir, Hawk, & Beck, 2009;
Lazarus & Folkman, 1984; Ravindran et al., 1995; Ravindran et
al., 2002), the construct may be confounded with current levels of
distress (Folkman & Moskowitz, 2004). Fourth, coping was as-
sessed with a self-report inventory. Although the CISS question-
naire used in this study has acceptable psychometric properties,
discussions about the optimal categories of coping and most ap-
propriate methods of assessment are still ongoing (Folkman &
Moskowitz, 2004).
A few additional limitations are worth mentioning. To our
knowledge, this is the first study that has examined the interaction
between coping style and oxytocin on the mood response to
interpersonal stress. As such, the results of the present study
require replication. Furthermore, the effect of intranasal oxytocin
on mood may be dose dependent (Goldman, Gomes, Carter, &
Lee, 2011), and the current study only investigated a single 24-IU
dose—that most commonly reported in the literature. Finally, as
89
COPING, OXYTOCIN, AND INTERPERSONAL STRESS
described previously, administration of the CISS at the end of our
study poses the possibility that oxytocin or the YIPS influenced
one of our predictor variables, emotion-oriented coping. However,
we have found no evidence that the drug administration or the
YIPS influenced emotion-oriented coping scores.
In sum, the present study provides evidence of the anxiolytic
effects of oxytocin in human females who endorse high levels of
emotion-oriented coping—who are in effect vulnerable to inter-
personal stress. To date, female populations have been largely
neglected in experimental studies of intranasal oxytocin. This
study highlights the need for more research in female and at-risk
populations. The implications of oxytocin as an anxiolytic agent in
vulnerable females is important to understanding the mechanisms
underlying social support, which, when jeopardized, poses as a risk
factor for psychopathology (Tull, Jakupcak, & McFadden, 2007).
Theoretically, oxytocin may serve as a fruitful avenue for research
in the treatment of psychopathology where adaptive social behav-
ior or social supports have been compromised.
References
Aiken, L. S., & West, S. G. (1991). Multiple regression: Testing and
interpreting interactions. Thousand Oaks, CA: Sage.
Alvares, G. A., Hickie, I. B., & Guastella, A. J. (2010). Acute effects of
intranasal oxytocin on subjective and behavioral responses to social
rejection. Experimental and Clinical Psychopharmacology, 18, 316 –
312. doi:10.1037/a0019719
Bartz, J. A., Zaki, J., Bolger, N., Hollander, E., Ludwig, N. N., Kolevzon,
A., & Ochsner, K. N. (2010). Oxytocin selectively improves empathic
accuracy. Psychological Science, 21, 1426 –1428. doi:10.1177/
0956797610383439
Baschnagel, J. S., Gudmundsdottir, B., Hawk, L. W., & Beck, J. G. (2009).
Post-trauma symptoms following indirect exposure to the September
11th terrorist attacks: The predictive role of dispositional coping. Jour-
nal of Anxiety Disorders, 23, 915–922. doi:10.1016/j.janx-
dis.2009.05.005
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L.
(2002). Sniffing neuropeptides: A transnasal approach to the human
brain. Nature Neuroscience, 5, 514 –516. doi:10.1038/nn0602–849
Buchheim, A., Heinrichs, M., George, C., Pokorny, D., Koops, E., Hen-
ningsen, P., . . . Gunndel, H. (2009). Oxytocin enhances the experience
of attachment security. Psychoneuroendocrinology, 34, 1417–1422. doi:
10.1016/j.psyneuen.2009.04.002
Carter, C. (1998). Neuroendocrine perspectives on social attachment and
love. Psychoneuroendocrinology, 23, 779 – 818. doi:10.1016/S0306-
4530(98)00055-9
Clarke, D., & Goosen, T. (2009). The mediating effects of coping strategies
in the relationship between automatic negative thoughts and depression
in a clinical sample of diabetes patients. Personality and Individual
Differences, 46, 460 – 464. doi:10.1016/j.paid.2008.11.014
Cyranowski, J. M., Frank, E., Young, E., & Shear, K. (2000). Adolescent
onset of the gender difference in lifetime rates of major depression.
Archives of General Psychiatry, 57, 21–27. doi:10.1001/arch-
psyc.57.1.21
Cyranowski, J. M., Hofkens, T. L., Frank, E., Cai, H-M., Amico, J. A., &
Seltman, H. (2008). Evidence of dysregulated peripheral oxytocin re-
lease among depressed women. Psychosomatic Medicine, 70, 967–975.
doi:10.1097/PSY.0b013e318188ade4
Ditzen, B., Schaer, M., Gabriel, B., Bodenmann, G., Ehlert, U., & Heinrichs,
M. (2009). Intranasal oxytocin increases positive communication and re-
duces cortisol levels during couple conflict. Biological Psychiatry, 65,
728 –731. doi:10.1016/j.biopsych.2008.10.011
Eberhart, N. K., & Hammen, C. L. (2006). Interpersonal predictors of onset
of depression during the transition to adulthood. Personal Relationships,
13, 195–206. doi:10.1111/j.1475-6811.2006.00113.x
Endler, N. S., & Parker, J. D. A. (1990). Coping Inventory for Stressful
Situations (CISS): Manual. Toronto: Multi-Health Systems.
Feder, A., Nestler, E. J., & Charney, D. S. (2009). Psychobiology and
molecular genetics of resilience. Nature Reviews Neuroscience, 10,
446 –257. doi:10.1038/nrn2649
Folkman, S., & Moskowitz, J. T. (2004). Coping: Pitfalls and promise.
Annual Review of Psychology, 55, 745–774. doi:10.1146/annurev-
.psych.55.090902.141456
Frash, A., Zetzsche, T., Steiger, A., & Jirikowski, G. F. (1995). Reduction
of plasma oxytocin levels in patients suffering from major depression.
In: Ivell, R., & Russell, J. (Eds.), Oxytocin - Cellular and Molecular
Approaches in Medicine and Research. New York, NY: Plenum Press
Division Plenum Press Publishing Corp.
Gimpl, G., & Fahrenholz, F. (2001). The oxytocin receptor system: Struc-
ture, function and regulation. Physiological Review, 81, 629 – 683.
Goldman, M. B., Gomes, A. M., Carter, C. S., & Lee, R. (2011). Divergent
effects of two different doses of intranasal oxytocin on facial affect
discrimination in schizophrenic patients with and without polydipsia.
Psychopharmacology, 216, 101–110.
Hammen, C. (2005). Stress and depression. Annual Review of Clinical Psy-
chology, 1, 293–319. doi:10.1146/annurev.clinpsy.1.102803.143938
Hammen, C., Shih, J. H., & Brennan, P. A. (2004). Intergenerational
transmission of depression: Test of an interpersonal stress model in a
community sample. Journal of Consulting and Clinical Psychology, 72,
511–522. doi:10.1037/0022-006X.72.3.511
Heim, C., Young, L. J., Newport, D. J., Mletzko, T., Miller, A. H., &
Nemeroff, C. B. (2009). Lower CSF oxytocin concentrations in women
with a history of childhood abuse. Molecular Psychiatry, 14, 954 –958.
doi:10.1038/mp.2008.112
Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003).
Social support and oxytocin interact to suppress cortisol and subjective
responses to psychosocial stress. Biological Psychiatry, 54, 1389 –1398.
doi:10.1016/S0006-3223(03)00465-7
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., . . .
Meyer–Lindenberg, A. (2005). Oxytocin modulates neural circuitry for
social cognition and fear in humans. The Journal of Neuroscience, 25,
11489 –11493. doi:10.1523/JNEUROSCI.3984-05.2005
Kosfeld, M., Heinrichs, M., Zak, P. K., Fischbacher, U., & Fehr, E. (2005).
Oxytocin increases trust in humans. Nature, 435, 673– 676. doi:10.1038/
nature03701
Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal, and coping. New
York, NY: Springer Inc.
Linnen, A-M., Ellenbogen, M. A., Cardoso, C., & Joober, R. (in press).
Intranasal oxytocin and salivary cortisol concentration during social
rejection in university students. Stress: The International Journal on the
Biology of Stress.
McNair, D. M., Lorr, M., & Heuchert, J. W. P. (1982). Profile of Mood
States, Bipolar Form (Manual). San Diego, CA: EdITS.
McWilliams, L. A., Cox, B. J., & Enns, M. W. (2003). Use of coping
inventory for stressful situations in a clinically depressed sample: Factor
structure, personality correlates, and prediction of distress. Journal of
Clinical Psychology, 59, 1371–1385. doi:10.1002/jclp.10228
Meinlschmidt, G., & Heim, C. (2007). Sensitivity to intranasal oxytocin in
adult men with early parental separation. Biological Psychiatry, 61,
1109 –1111. doi:10.1016/j.biopsych.2006.09.007
Meynen, G., Unmehopa, U. A., Hofman, M. A., Swaab, D. F., &
Hoogendijk, W. J. (2007). Hypothalamic oxytocin mRNA expression
and melancholic depression. Molecular Psychiatry, 12, 118 –119. doi:
10.1038/sj.mp.4001911
Norman, G. J., Cacloppo, J. T., Morris, J. S., Malarkey, W. B., Berntson,
G. G., & DeVries, A. C. (2011). Oxytocin increases autonomic cardiac
90 CARDOSO, LINNEN, JOOBER, AND ELLENBOGEN
control: Moderation by loneliness. Biological Psychiatry, 86, 174 –180.
doi:10.1016/j.biopsycho.2010.11.006
Orth–Gomer, K., Wamala, S. P., & Horsten, M. (2000). Marital stress
worsens prognosis in women with coronary heart disease: The Stock-
holm female coronary risk study. The Journal of the American Medical
Association, 284, 3008 –3014. doi:10.1001/jama.284.23.3008
Ostiguy, C., Ellenbogen, M. A., Linnen, A.-M., Walker, E. F., Hammen,
C., & Hodgins, S. (2009). Chronic stress and stressful life events in the
offspring of parents with bipolar disorder. Journal of Affective Disor-
ders, 114, 74 – 84. doi:10.1016/j.jad.2008.08.006
Ozsoy, S., Esel, E., & Kula, M. (2009). Serum oxytocin levels in patients with
depression and the effects of gender and antidepressant treatment. Psychiatry
Research, 169, 249 –252. doi:10.1016/j.psychres.2008.06.034
Panksepp, J., Nelson, E., & Bekkedal, M. (1997). Brain systems for the
mediation of social separation-distress and social-reward—Evolutionary
antecedents and neuropeptide intermediaries. In: C. S. Carter, I. I.
Lederhendler, & B. Kirkpatrick (Eds.), Integrative neurobiology of
affiliation (pp. 221–244). New York, NY: New York Academy of
Sciences..
Parker, K. J., Kenna, H. A., Zeitzer, J. M., Keller, J., Blasey, C. M., Amico,
J. A., & Schatzberg, A. F. (2010). Preliminary evidence that plasma
oxytocin levels are elevated in major depression. Psychiatry Research,
178, 359 –362. doi:10.1016/j.psychres.2009.09.017
Purba, J. S., Hoogendijk, W. J. G., Hofman, M. A., & Swaab, D. F. (1996).
Increased number of vasopressin- and oxytocin-expressing neurons in
the paraventricular nucleus of the hypothalamus in depression. Archives
of General Psychiatry, 53, 137–143.
Quirin, M., Kuhl, J., & Dusing, R. (2011). Oxytocin buffers cortisol
responses to stress in individuals with impaired emotion regulation
abilities. Psychoneuroendocrinology, 36, 898 –904.
Ravindran, A. V., Griffiths, J., Waddell, C., & Anisman, H. (1995).
Stressful life events and coping styles in relation to dysthymia and major
depressive disorder: Variations associated with alleviation of symptoms
following pharmacotherapy. Progress in Neuro-Psychopharmacology &
Biological Psychiatry, 19, 637– 653. doi:10.1016/0278-
5846(95)00108-8
Ravindran, A. V., Matheson, K., Griffiths, J., Merali, Z., & Anisman, H.
(2002). Stress, coping, uplifts, and quality of life in subtypes of depres-
sion: A conceptual frame and emerging data. Journal of Affective Dis-
orders, 71, 121–130. doi:10.1016/S0165-0327(01)00389-5
Scantamburlo, G., Hansenne, M., Fuchs, S., Pitchot, W., Marechal, P.,
Pequeux, C., . . . Legros, J. J. (2007). Plasma oxytocin levels and anxiety
in patients with major depression. Psychoneuroendocrinology, 32, 407–
410. doi:10.1016/j.psyneuen.2007.01.009
Stroud, L. R., Salovey, P., & Epel, E. S. (2002). Sex differences in stress
responses: Social rejection versus achievement stress. Biological Psy-
chiatry, 52, 318 –327. doi:10.1016/S0006-3223(02)01333-1
Stroud, L. R., Tanofsky–Kraff, M., Wilfley, D. E., & Salovey, P. (2000).
The Yale Interpersonal Stressor (YIPS): affective, physiological, and
behavioural responses to a novel interpersonal rejection paradigm. An-
nals of Behavioral Medicine, 22, 204 –213. doi:10.1007/BF02895115
Tamres, L. K., Janicki, D., & Helgeson, V. S. (2002). Sex differences in
coping behavior: A meta-analytic review and an examination of relative
coping. Personality and Social Psychology Review, 6, 2–30. doi:
10.1207/S15327957PSPR0601_1
Taylor, S. E., Klein, L. C., Lewis, B. P., Gruenewald, T. L., Gurung,
R. A. R., & Updegraff, J. A. (2000). Biobehavioral responses to stress in
females: Tend-and-befriend, not fight-or-flight. Psychological Review,
107, 411– 429. doi:10.1037/0033-295X.107.3.411
Tull, M. T., Jakupcak, M., & McFadden, M. E. (2007). The role of negative
affect intensity and the fear of emotions in posttraumatic stress symptom
severity among victims of childhood interpersonal violence. The Journal
of Nervous and Mental Disease, 195, 580 –587. doi:10.1097/
NMD.0b013e318093ed5f
Veenstra, M. Y., Lemmens, P. H., Friesema, I. H., Tan, F. E., Garretsen,
H. F., Knottnerus, J. A., & Zweitering, P. J. (2007). Coping style
mediates impact of stress on alcohol use: a prospective population-based
study. Addiction, 102, 1890 –1898. doi:10.1111/j.1360-
0443.2007.02026.x
Received February 8, 2011
Revision received August 17, 2011
Accepted August 18, 2011 䡲
Correction to Hicks et al. (2011)
In the article “Expecting innovation: Psychoactive drug primes and the generation of creative
solutions,” by Joshua A. Hicks, Sarah L. Pedersen, Ronald S. Friedman, and Denis M. McCarthy
(Experimental and Clinical Psychopharmacology, Vol. 19, No. 4, pp. 314 –320), the name of author
Sarah L. Pedersen was misspelled as Sarah L. Pederson. All versions of this article have been
corrected.
DOI: 10.1037/a0026740
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COPING, OXYTOCIN, AND INTERPERSONAL STRESS
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