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R E S E A R C H A R T I C L E Open Access
Autonomic vulnerability to biased
perception of social inclusion in borderline
personality disorder
Maria Lidia Gerra
1*
, Martina Ardizzi
2
, Silvia Martorana
2
, Veronica Leoni
2
, Paolo Riva
3
, Emanuele Preti
3
,
Barbara Francesca Marta Marino
3
, Paolo Ossola
2
, Carlo Marchesi
2
, Vittorio Gallese
2
and Chiara De Panfilis
2
Abstract
Background: Individuals with Borderline Personality Disorder (BPD) feel rejected even when socially included. The
pathophysiological mechanisms of this rejection bias are still unknown. Using the Cyberball paradigm, we
investigated whether patients with BPD, display altered physiological responses to social inclusion and ostracism, as
assessed by changes in Respiratory Sinus Arrhythmia (RSA).
Methods: The sample comprised 30 patients with BPD, 30 with remitted Major Depressive Disorder (rMDD) and 30
Healthy Controls (HC). Self-report ratings of threats toward one’s fundamental need to belong and RSA reactivity
were measured immediately after each Cyberball condition.
Results: Participants with BPD showed lower RSA at rest than HC. Only patients with BPD, reported higher threats
to fundamental needs and exhibited a further decline in RSA after the Inclusion condition.
Conclusions: Individuals with BPD experience a biased appraisal of social inclusion both at the subjective and
physiological level, showing higher feelings of ostracism and a breakdown of autonomic regulation to including
social scenarios.
Keywords: Respiratory sinus arrhythmia, Rejection bias, Cyberball paradigm, Polyvagal theory
Background
Borderline Personality Disorder (BPD) is a severe mental
illness affecting approximately 1% of the general popula-
tion [1]. Social dysfunction represents one of the most
enduring and challenging to treat feature of the disorder,
which is not substantially affected by a symptomatic de-
crease or even remission over time [2]. In BPD, social
impairment is fostered by a unique interpersonal hyper-
sensitivity pattern, encompassing extensive preoccupa-
tion with real or imagined abandonment and rejection,
and related distrustful perceptions of others as bad, mal-
evolent, and excluding [3–5]. Therefore, clarifying the
potential mechanisms fostering this peculiar way of pro-
cessing interpersonal cues is a primary clinical and re-
search goal in BPD study.
Rejection bias in BPD
Recent studies evaluated BPD patients’responses to
varying degrees of interpersonal inclusion using Cyber-
ball, a virtual ball-tossing game where participants can
be socially excluded, included, or even over-included by
others [6,7]. Results indicate that patients with BPD do
not merely “over-react”to actual social exclusion; rather,
they feel rejected and experience greater rejection-
related negative emotions than controls following object-
ive interpersonal inclusion [8–10]. Moreover, individuals
with BPD feel disconnected from others even when they
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0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
* Correspondence: magerra@ausl.pr.it
1
Department of Mental Health, AUSL of Parma, Parma, Italy
Full list of author information is available at the end of the article
Gerra et al. Borderline Personality Disorder and Emotion Dysregulation
(2021) 8:28
https://doi.org/10.1186/s40479-021-00169-3
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
face a condition of extreme interpersonal inclusion [11,
12]. Overall, these findings suggest a “misperception of
social participation”: patients with BPD show biased pro-
cessing of social inclusion, which makes them perceive
rejection even in interpersonal situations that are object-
ively including.
Autonomic correlates of rejection bias in BPD
To date, most BPD studies focused on subjective (i.e.,
explicit, self-reported) emotional reactions to the Cyber-
ball experiment, while the underlying implicit patho-
physiological mechanisms of this rejection bias are yet to
be fully elucidated.
The Polyvagal Theory [13] provides a theoretical
framework to study the Autonomic Nervous System
(ANS) reactivity to perceived threatening interpersonal
cues. According to such theory, the myelinated vagal
system evolved to support flexible adaptation to environ-
mental stimuli. When the environment is appraised as
safe, at the cardiac level, the “vagal brake”increases the
parasympathethic activity on the hearth, slows down the
heart rate, and inhibits the more primitive ANS systems
(i.e., the sympathetic nervous system and the unmiely-
nated vagus) that promote fight/fly or freeze defense
strategies. Ultimately, this serves to support effective so-
cial engagement behaviors. In this way, prosocial-
affiliative interactions can adaptively emerge and persist
over time in safe contexts.
The dynamic functional impact of the myelinated
vagal fibers on the heart is reflected by the amplitude of
the Respiratory Sinus Arrhythmia (RSA), a naturally oc-
curring rhythm in the cardiac cycle at approximately the
frequency of spontaneous breathing [14–16]. Thus,
measurement of the amplitude of RSA provides an as-
sessment of the state of the vagal brake: increased vagal
influence on the heart corresponds to high or increased
RSA. By contrast, in challenging or threatening situa-
tions, the vagal brake is withdrawn, leading to physio-
logical states that support the fight, flight, or freeze
behaviors but inhibiting social engagement behaviors.
This vagal withdrawal is reflected in RSA decreases.
Thus, high RSA at rest and in safe environments and the
appropriate RSA suppression in the face of real environ-
mental risks represent a marker of successful self-
regulation. Notably, this flexible and adaptive increase or
decrease in RSA crucially depends on the environmental
risks’accurate appraisal.
The neural ability to distinguish environmental fea-
tures that are safe, dangerous, or life-threatening is
called neuroception, a process of neural detection of risk
that does not require conscious awareness [13]. When
neuroception is impaired, the ANS fails to distinguish
between safe and dangerous contexts accurately: thus,
the environment may be appraised as dangerous when it
is safe. This leads to a mismatch between the actual risk
of the environment and the neurophysiological state,
resulting in an inability to appropriately inhibit the
defense systems and maintain prosocial behaviors in safe
environments. It is possible to measure such mismatch
by assessing RSA both at rest and during various envir-
onmental challenges: low RSA in the absence of environ-
mental demands or in response to stimuli that are not
threatening would suggest that individuals physiologic-
ally appraise and react to safe environments as if they
were actually unsafe [13].
In this regard, accumulating evidence indicates that
patients with BPD exhibit low cardiac vagal tone at rest
[17–21], indicating that they present a constant physio-
logical condition of preparedness to face threats and
danger. In the same vein, having low RSA at rest medi-
ates the association between BPD symptoms and reactive
aggression in a non-clinical population [22], suggesting
that impaired vagal control leads to maladaptive social
behaviors in individuals with BPD features.
Three other studies on BPD examined RSA reactivity,
that is, RSA change in response to various experimental
stimuli, like film clips of varying emotional content [23],
mental arithmetic tasks [18], and standardized film and
idiographic imagery paradigms [17]. Overall, these stud-
ies found that, among participants with BPD, RSA
remained as low as at baseline [17] or even decreased
during the experiment [18,23]. These studies suggest
that engaging in an emotional or cognitive experimental
task induces, among patients with BPD, a physiological
state that promotes defensive behaviors, with phylogen-
etically older ‘fight-or-flight’response, rather than a vis-
ceral state that supports self-regulation and spontaneous
social engagement behaviors.
To our knowledge, no study yet evaluated RSA reactiv-
ity in response to varying degrees of social inclusion in
BPD. Such inquiry could clarify whether BPD patients
subjectively perceive including social scenarios as if they
were rejecting by reacting to them with a breakdown of
the self-regulation and socialization capacities, rooted in
the myelinated vagal system’s activity.
It is also important to examine whether such hypothe-
sized in including situations, associated with vagal with-
drawal, truly represents a BPD-specific alteration, by
comparing BPD with a clinical and medicated control
group, with similar illness duration. In this regard, pa-
tients with Major Depressive Disorder (MDD) have also
been found to exhibit peculiar responses to the Cyber-
ball experiment and altered RSA patterns as compared
with Healthy Controls (HC).
As compared with HC, patients with active MDD (i.e.,
during full-blown depressive episodes) experience a
greater sense of threat to psychological fundamental
needs after social exclusion [24–29]. Interestingly,
Gerra et al. Borderline Personality Disorder and Emotion Dysregulation (2021) 8:28 Page 2 of 14
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although one study also found that MDD patients report
greater perception of threat after social inclusion than
HC [30], another study argued that such rejection bias
in including situations among patients with active MDD
was explained by BPD comorbidity [31]. Only one study
evaluated how patients with MDD in the remission
phase (rMDD) react to the Cyberball experiment [32].
However, this study assessed social distress related to
the task as a whole, and not after the inclusion and os-
tracism conditions. Thus, it is not known yet whether
the increased sensitivity to ostracism (and possibly the
rejection bias) showed by MDD patients during an active
depressive episode would persist even in the euthymic
phase, thus representing a trait-based phenomenon ra-
ther than just a state-dependent phenomenon that is ap-
parent only during full-blown episodes.
With respect to RSA findings, patients with active MDD
were found to exhibit low resting RSA and atypical RSA
reactivity to various laboratory stressors. Further, during
the remission phase patients with MDD exhibit low rest-
ing RSA but not altered RSA reactivity to laboratory tasks
[33–38]. Thus, low RSA at rest seems to represent a
stable, trait-like feature of MDD, which persists even dur-
ing the euthymic phase, when patients with rMDD may
still exhibit distinctive clinical features, such as sub-
threshold psychopathology [35], peculiar personality styles
[36], or symptomatological scars of previous episodes [37].
Conversely, altered RSA reactivity during active phases of
depression is likely to represent a state-effect of full-blown
depressive psychopathology [34]. However, no study yet
measured RSA reactivity to Cyberball in MDD.
Thus, it is not yet clear whether MDD patients exhibit
peculiar patterns of responses to Cyberball associated
with altered RSA reactivity, which persist at the remis-
sion of depressive episodes.
Therefore, in this study we compared BPD patients,
with no current depressive episode, with rMDD patients
on maintenance treatment, with no BPD comorbidity, to
investigate whether RSA alterations following the Cyber-
ball conditions could represent a stable, trait-like elem-
ent that could distinguish the clinical groups, over and
above the confounding effect of full-blown depressive
symptomatology. Importantly, such comparison also al-
lows for controlling for the potential confounding effect
of sub-threshold depressive symptoms. Patients with
BPD often present with depressive symptoms, although
known to be transient, stress reactive and arising from a
primary diagnosis of BPD [39,40]; in the same vein, pa-
tients with rMDD also may experience inter-episodic de-
pressive psychopathology [35].
The present study
This study investigated whether patients with BPD, com-
pared to HC and patients with rMDD, show an altered
emotional response associated with an altered vagal re-
activity after Cyberball conditions of Social Inclusion
and Ostracism, as well as 10 min after Ostracism (Re-
flective stage). Based on previous research, three main
predictions guided our investigation.
First, we expected to replicate the finding that BPD pa-
tients, compared to healthy and clinical controls, would
report reduced levels of satisfaction of fundamental psy-
chological needs (e.g., the need to belong) even in in-
cluding situation both immediately after Ostracism, as
well as at the Reflective stage. This would confirm a
biased perception of social inclusion at the subjective
(i.e., explicit) level in BPD.
Second, we expected that patients with BPD, com-
pared to healthy and clinical controls, would exhibit re-
duced RSA at rest (i.e., before starting the game),
indicating stable difficulties in social predisposition at
the physiological level. Moreover, we expected that at
the ANS level, patients with BPD would show a further
decrease in RSA after the Cyberball Inclusion condition
than baseline RSA. This would indicate that individuals
with BPD physiologically respond to including social sit-
uations as if they were threatening, with a dysfunctional
withdrawal of the vagal brake that leads to increased
physiological arousal, mobilizing defensive reactions but
impeding successful social engagement.
Finally, we hypothesized that a higher perception of
threat to fundamental psychological needs induced by
the Cyberball task would be associated with higher
physiological arousal as indicated by vagal withdrawal
(i.e., a more substantial decline in RSA).
Methods
Participants
This study involved 30 patients with BPD, 30 patients
with rMDD, and 30 HC. Patients were recruited at the
psychiatry outpatient services of Parma Local Health
Agency (Parma, Italy) from January 2016 to September
2018. HC, matched for age and gender with patients
with BPD, were recruited through advertisements in
meeting places in the local community.
Inclusion and exclusion criteria
Inclusion criteria were: 1) age 18–65 years; 2) native Ital-
ian speaker or proficient in Italian; 3) for the clinical
groups, meeting the diagnostic criteria for rMDD or
BPD, assessed by the Structured Clinical Interview for
DSM-5 disorders, Clinician Version (SCID-5-CV) [41]
and the Structured Clinical Interview for DSM-5 Person-
ality Disorders (SCID-5-PD) [42], respectively; 4) scor-
ing< 7 on the 21-item Hamilton Rating Scale for
Depression (HAM-D) [43] and < 7 in the Hamilton Anx-
iety Rating Scale (HAM-A) [44].
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Exclusion criteria were: 1) any cardio-respiratory
diseases and treatment that directly affect the ANS’s
function (e.g., sympatho-mimetic and para-sympatho-
mimetic drugs, alpha and beta receptors blockers, and
anti-muscarinic drugs); 2) cognitive impairment,
assessed by the Wechsler Adult Intelligence Scale Matrix
Reasoning Subtest [45]; 3) any current diagnoses of
Schizophrenia spectrum and other Psychotic Disorders,
Bipolar Disorders, Anxiety Disorders, Post-Traumatic
Stress Disorder, Somatic Symptom and related Disorders
and Eating Disorders. For the BPD group, both current
and lifetime MDD comorbidity also was an exclusion
criterion. However, for both clinical groups, we included
patients with other previous lifetime disorders, though
fully remitted at the study time (i.e., Adjustment disor-
ders, Substance-related disorders, Eating Disorders,
Obsessive-Compulsive Disorder). Patients were not ex-
cluded for regular psychotropic medication use.
Participants were told that the researchers were in-
vestigating “Mental visualization and individual differ-
ences in heart rate and psychological responses.”This
cover story is thought to maximize the experiment’s
ecological validity [46]. Participants gave written in-
formed consent to participation and, after completion
of the experiment, were extensively debriefed and
given detailed information about the study and its
purposes, with the opportunity to have their data de-
leted should they wish so.
The total sample size collected (N= 90) exceeded the
minimum amount required (N= 54) estimated using a
priori sample size calculation, obtained for repeated-
measures analyses of variance (ANOVA) considering
both within and between interactions (1-ß = .95, α= .05,
effect size F = .25). The sample size was computed with
G*power [47] based on the effect size of previous studies
that compared BPD with two other clinical groups [48].
We enlarged the a-priori required sample size up to 30
per group to account for covariates, such as age, Body
Mass Index (BMI), alcohol and tobacco consumption,
known to affect RSA.
Psychometric assessment
All participants completed a general demographic ques-
tionnaire on age, gender, BMI, physical activity, educa-
tional level, occupational and marital status, and
habitual consumption of psychotropic substances (alco-
hol, caffeine, and nicotine).
Psychosocial functioning was assessed with the Global
Assessment of Functioning Scale (GAF) [49].
Experimental procedure
Participants were led into a quiet and soft illuminated
room and were instructed to relax and remain seated
comfortably. At the beginning of the experimental ses-
sion, participants were instructed to sit quietly with their
eyes open, and a 2-min resting baseline electrocardio-
gram (ECG) was recorded to assess RSA at rest.
Subsequently, they participated in a Cyberball experi-
ment and completed different measures of their current
emotional state. ECG recordings were collected over the
entire duration of the experimental session to extract
phasic autonomic measures (i.e., RSA reactivity). Please
refer to Fig. 1for a graphical display of the experimental
procedure.
Cyberball experiment
Inclusionary status was manipulated using a classic para-
digm called Cyberball (Cyberball (version 4.0) [Software]
available from https://cyberball.wikispaces.com). This
virtual ball-tossing game has been developed to induce
feelings of ostracism in controlled settings [7]. Following
the typical procedure [46], participants were told that in-
vestigators were interested in the effects of mental
visualization on a subsequent task and that a good way
to warm up was to engage in a mental visualization exer-
cise with other online players. In actuality, these two
Fig. 1 Experimental procedure
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other players were not real; instead, they were
computer-controlled confederate players, identified
using a name. All participants were enrolled in two con-
secutive conditions of the Cyberball game: initially, they
were included in a belonging game (i.e., receiving the
ball about a third of the time, roughly 33% of the total
throws) and then ostracized (i.e., receiving the ball once
from each computer-controlled player and then never
again, roughly 10% of the total throws). The order of the
Inclusion-Ostracism conditions was kept fixed for all
participants (for a similar procedure, see: [50]).
Manipulation checks
After each Cyberball condition, participants rated the
percentage of throws (0–100%) they received during the
game as a manipulation check. They were then asked to
report how excluded (“I felt excluded”) and ignored (“I
felt ignored”) they felt during each Cyberball session. Re-
sponses were rated on 10-point scales (ranging from 1 =
not at all to 10 = very much). The two items were com-
bined in an overall index of feelings of being excluded
and ignored. Higher scores indicate greater feelings of
ostracism.
Subjective responses to the Cyberball game
Participants were asked to report their feelings three
times: after Cyberball Inclusion, immediately after
Cyberball Ostracism, and 10 min after completing the
experiment (i.e., Reflective stage).
The Need-Threat Scale (NTS) measures satisfaction
with the four fundamental needs potentially affected
by ostracism in a 12-item scale: the need to have
pleasant interactions with others (belonging), the need
tobelieveothersviewusasworthy(self-esteem),the
need to influence our social environment (control),
and the need to avoid our fear of death by making an
impact on the world (meaningful existence) [51].
Lower scores reflect the “ostracism distress”,e.g.a
greater perceptions of threat to these fundamental
needs. In this sample, the internal consistency of NTS
was good across all assessment times (α
inclusion
= .79;
α
ostracism
=.81; α
reflective stage
= .87).
Autonomic responses to the Cyberball game
Patients were fitted with three 10 mm Ag/AgCl pre-
gelled adhesive electrodes for an ECG (ADInstruments,
UK) placed in an Einthoven’s triangle configuration.
The ECG was sampled at 2 kHz and online filtered
with the Mains Filter. RSA values were extracted for
the entire duration of the baseline-block (120 s), for
the last 120 s of the condition-blocks (Inclusion and
Ostracism) and at Reflective stage (120 s), in line with
guidelines [52].
The peak of the R-wave of the ECG was detected from
each sequential heartbeat. The R-R intervals were ex-
tracted, and the artifacts were edited by integer division
or summation. Editing consisted of visual detection of
outlier points, typically caused by failure to detect an R-
peak (e.g., edit via division) or faulty detections of two or
more peaks within a period representing the R-R interval
(e.g., edit via summation). The amplitude of RSA
[expressed in ln (msec)
2
], calculated as the natural loga-
rithm of the variance of heart rate activity across the fre-
quency band associated with spontaneous respiration,
was quantified with CMetX [53,54].
Statistical analysis
Descriptive statistics were performed to detail the socio-
demographic and clinical characteristics of the sample.
Cyberball experiment
Manipulation checks
Two 3*2 repeated measure analyses of variance
(ANOVA) with a Group (BPD vs. rMDD vs. HC) by
Condition (Inclusion vs. Ostracism) design were per-
formed, with the post-Cyberball ratings of percentages
of ball tosses received and feelings of being excluded/ig-
nored as dependent variables.
Subjective responses
A 3*3 repeated-measures ANOVA was conducted with
Need-Threat Scale (NTS) scores as the dependent vari-
able to examine how the perceived threats to fundamen-
tal needs were influenced by the clinical status (Group:
BPD vs. rMDD vs. HC) and by the experimental Condi-
tion (Inclusion vs. Ostracism vs. Reflective Stage).
Autonomic responses
Finally, a 3*4 Group (BPD vs. rMDD vs. HC) by Condi-
tion (Baseline vs. Inclusion vs. Ostracism vs. Reflective
Stage) ANCOVA was used to identify whether the pat-
tern of changes in RSA throughout the game varied
among groups. Age, BMI, alcohol and tobacco consump-
tion were considered as covariates because they could
affect RSA and differed among diagnostic groups.
Simple effects analyses were used to evaluate signifi-
cant main and interaction effects. All the analyses were
carried out using SPSS software (IBM SPSS 25.0).
Association between subjective and autonomic responses to
Cyberball conditions
Finally, we performed three linear regression analyses
(enter method) to evaluate whether NTS scores pre-
dicted RSA following Inclusion, Ostracism and at the
Reflective Stage, whilst controlling for confounding vari-
ables. In all the analyses, we entered the covariates
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
mentioned above - age, BMI, alcohol and tobacco con-
sumption –as well as RSA at baseline.
Results
Sample
The socio-demographic and clinical characteristics of
the participants are shown in Table 1.
The sample consisted of 90 participants, of which
85.6% were women. This gender distribution reflects the
epidemiology of BPD in clinical treatment population:
although in the general population there is no d iffer-
ence in the prevalence of BPD between males and fe-
males [55], in clinical settings BPD is diagnosed
predominantly in females [49], likely for the greater
proneness of women with BPD to seek outpatient treat-
ment [56]. HC and patients with rMDD were matched
for sex to the BPD sample, resulting in no gender differ-
ences in the three groups. In terms of age, patients with
rMDD were older than both the BPD and HC groups,
and, accordingly, less likely to live alone/with parents or
to be students. They also had a greater BMI and re-
ported to consume alcoholic beverages and tobacco to a
lesser extent than the other groups. These differences
seem to be mostly related to the age difference. As com-
pared to the clinical groups, HC were more likely to
have a college/university level of education and were all
employed, with a greater level of global functioning.
Cyberball experiment
Manipulation checks
As expected, there was a significant effect of the experi-
mental Condition on participants’ratings of both per-
ception of percentages of ball throws received (F
1.87
=
431.22, p< .01, η
2partial
= .83) and feelings of being ig-
nored and excluded (F
1.87
= 184.27, p< .01, η
2partial
= .68).
As compared to the Inclusion condition, after Ostracism
participants reported that they received a lower percent-
age of ball tosses (Ostracism 2.58 ± .37 < Inclusion
40.26 ± 1.83), and that they felt more ignored and ex-
cluded (Ostracism 4.34 ± .23 > Inclusion 1.29 ± .08).
These results suggest that the Cyberball manipulation
was successful.
Importantly, this effect held irrespective of the partici-
pants’clinical status, as indicated by the absence of any
significant Group effect (percentage of throws received:
F
2.87
= 1.91, p= .15, η
2partial
= .04; feeling of being ig-
nored/excluded: F
2.87
= 1.13, p= .33, η
2partial
= .03) nor
Group by Condition interaction (percentage of throws
received: F
2.87
= 2.06, p= .13, η
2partial
= .05; feeling of be-
ing ignored/excluded: F
2.87
= .59, p= .55, η
2partial
= .01.
Thus, HC and participants with BPD and rMDD were
equally cognitively aware of their inclusionary status
during the game.
Subjective responses to the Cyberball game
Overall, participants reported that their fundamental
needs were more threatened in the Ostracism than in
the Inclusion condition (p< .01, CI = 1.53, 2.14) and
were then restored at the Reflective stage, as compared
with the Ostracism condition (p< .01, CI = -.51, −.11)
(main within-subject effect of Condition; Table 2;
Fig. 2A). Perception of threats to fundamental needs also
varied across groups, with a tendency of BPD to report
lower NTS scores (main between-subjects effect of
Group without significant post hoc comparisons; Table
2). However, these main effects were better qualified by
significant Group by Condition interaction (Table 2): pa-
tients with BPD reported lower satisfaction with funda-
mental needs than HC and patients with rMDD in the
Inclusion condition (HC: p< .01, CI = -1.22,-.15; rMDD:
p= .02, CI = -1.13,-.06), but not in the Ostracism condi-
tion (HC: p= 1, CI = -.93,.52; rMDD: p= .62, CI = -
1.10,.35) nor at Reflective stage (HC: p= .13, CI = -
1.26,1.45; rMDD: p= 1, CI = -.81,.77) (effect of Group
within the Group by Condition Interaction for the Inclu-
sion condition: F
2,87
= 5.75, η
2partial
= .12, p< .01). More-
over, satisfaction with fundamental needs increases from
the Ostracism to the Reflective stage in HC and patients
with rMDD (HC: p< .01, CI = -.86, −.16; rMDD: p= .04,
CI = -.70,-.07), but not among patients with BPD (p=1;
CI = -.40, .30) (Effect of Condition within the Group by
Condition interaction for the BPD group: F
2,86
= 32.4,
η
2partial
= .43, p< .01) (Fig. 2A).
Autonomic responses to the Cyberball game
Overall, patients with BPD presented a lower vagal
tone as compared to HC (p< .01; CI = -2.22, −.63),
but not to rMDD (p= .09; CI = -1.79, 0.85) (main
between-subject effect of Group on RSA levels; Table
2;Fig.2B). Specifically, BPD patients had lower rest-
ing RSA levels than HC (p= .02; CI = .14, 1.90), but
did not differ from rMDD at baseline (p=.81; CI=-
.57, 1.52; Effect of Group within a Group by Condi-
tion interaction for baseline RSA F
2.83
=4.43, η
2partial
=
.10, p=.02; Table 2). However, patients with BPD
showed a generally lower RSA than both HC and pa-
tients with rMDD across all the experimental condi-
tions (vs HC, all p
s
< .001; vs rMDD: Inclusion p=
.086; Ostracism p= .04, Reflective stage p= .05). Fur-
thermore, only in the BPD group RSA levels de-
creased during the experiment (Effect of Condition
within the Group by Condition interaction for the
BPD group: F
3,81
= 4.26, η
2partial
= .14, p<.01), while
they did not vary in HC nor rMDD patients (respect-
ively, F
3,81
=1.76, η
2partial
= .06, p=.16 and F
3,81
= 1.09,
η
2partial
= .04, p= .36). In particular, patients with BPD
exhibited a marked reduction in RSA from Baseline
to Inclusion (p= .01; CI = .08, 1.01); then, their RSA
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Table 1 Socio-demographic, clinical and psychometric characteristics
BPD HC rMMD Between-groups differences
n=30 n=30 n= 30 Main effect of factor Group* Post-hoc comparisons
Physiological variables
Age 33.2 ± 12.07 38.9 ± 14.65 49.27 ± 9.96 F
(2,87)
= 12.98, p < .01; ή
2p
= .23 rMDD>BPD, HC (p
s
< .01)
Sex (F) 27 (90%) 24 (80%) 26 (86.7%) χ
2
(2) = 1.26, p= .53
Sport 12 (40%) 17 (56.7%) 11 (36.7%) χ
2
(4) = 4.57, p = .33
BMI 21.77 ± 3.75 22.70 ± 3.40 26.31 ± 6.25 F
(2,87)
= 7.98, p = .01; ή
2p
= .15 rMDD>BPD, HC (p
s
< .01)
Psychotropic drugs consumption
Alcohol 17 (56.7%) 21 (70%) 7 (23.3%) χ
2
(2) = 13.87, p = .01
Caffeine 24 (80%) 26 (86.7%) 19 (63.3%) χ
2
(2) = 4.84, p = .09
Tobacco 26 (86.7%) 8 (26.7%) 5 (16.7%) χ
2
(2) = 35.02, p < .01
Social variables
Education (yrs) 11.53 ± 2.89 14.76 ± 3.54 11.23 ± 3.35 F
(2,87)
= 10.77, p < .01; ή
2p
= .20 HC> BPD, rMDD (p
s
< .01)
Family status
Married/living together 7 (23.3%) 16 (53.3%) 20 (66.6%) χ
2
(6) = 16.29, p = .01
Separated/divorced 6 (20%) 1 (3.3%) 4 (13.4%)
Widowed 0 (0%) 1 (3.3%) 1 (3.3%)
Living alone/with parents 17 (56.7%) 12 (40%) 5 (16.7%)
Occupation
Employed 16 (53.3%) 17 (53.4%) 22 (73.3%) χ
2
(6) = 29.13, p = .01
Housewife 0 (0%) 4 (13.3%) 6 (20%)
Students 6 (20%) 10 (33.3%) 0 (0%)
Unemployed 8 (26.7%) 0 (0%) 2 (6.7%)
Clinical and psychometric variables
DSM-5 Comorbidity
Adjustment disorder 12 (40%) ––
Substance Use disorders (in full remission) 10 (33.3%) ––
Alcohol Use disorders (in full remission) 3 (10%) ––
Obsessive Compulsive Disorder ––1 (3.3%)
Eating disorders 2 (6.7%) ––
Personality disorders 11 (36.7%) –3 (10%)
Passive-aggressive 2 (6.7%) ––
Paranoid 1 (3.3%) ––
Histrionic 2 (6.7%) ––
Narcissistic 6 (20%) ––
Dependent 1 (3.3%) ––
Obsessive-Compulsive ––3 (10%)
Medications
Mood stabilizers 25 (83.3%) –4 (13.3%) χ
2
(1) = 28.5, p < .01
Antidepressants 13 (43.3%) –30 (100%) χ
2
(1) = 24.7, p < .01
Antipsychotics 22 (73.3%) –4 (13.3%) χ
2
(1) = 21.08, p< .01
Benzodiazepines 21 (70%) –14 (46.7%) χ
2
(1) = 4.05, p = .04
Duration of illness 15.20 ± 12.1 11.77 ± 8.77 F
(1.58)
= 1.59, p= .21; ή
2p
= .03
Matrix reasoning 16.80 ± 2.42 20.10 ± 2.94 18.17 ± 3.38 F
(2,87)
= 9.52, p < .01; ή
2p
= .18 HC > BPD, rMD D (p
s
< .04)
GAF 72.07 ± 7.31 96.6 ± 4.76 86.57 ± 6.39 F
(2,87)
= 117.11, p < .01; ή
2p
= .73 HC > rMDD>BPD (p
s
< .01)
Notes
*F-Tests in One-way ANOVA have been performed to compare continuous variables; Chi square tests (χ2) have been performed to compare categorical variables.
BPD = patients with Borderline Personality Disorder; HC = Healthy Controls; rMDD = patients with Major Depressive Disorder in remission; BMI = Body Mass Index;
GAF = Global Assessment of Functioning
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levels did not vary and remained low moving from
the Inclusion to the Ostracism condition (p=1, CI=-
.51, .31) and from Ostracism to the Reflective stage
(p= 1, CI = -.62, .22) (Fig. 2B).
Association between subjective and autonomic responses to
Cyberball condition
Having found that participants with BPD, as compared
with non-BPD controls, reported greater threats to their
fundamental needs as well as a marked decrease in RSA
after the Cyberball Inclusion condition, we next
evaluated whether the subjective perception of threat in
the overall sample was associated with a breakdown of
vagal control at the physiological level. NTS scores pre-
dicted RSA levels only in the Inclusion condition (b=
.22, p= .04), but not after Ostracism (b= .08, p= .48) nor
at the Reflective stage (b= .04, p= .69). This held true
even after controlling, as above, for age, BMI, alcohol
and tobacco consumption and also for the baseline levels
of RSA (Inclusion: b= .11, p= .05; Ostracism: b=−.05,
p= .32; Reflective stage: b= .05, p= .41), indicating that
higher perception of threats to fundamental needs after
Table 2 Effect of Experimental Condition, Group Status and Their Interactions on NTS scores and RSA levels
Variables BPD HC rMDD Condition Group Interactions Condition X Group
NTS scores F
2,86
= 121.34
a
η
2partial
= .74
p< .01
F
2,87
= 3.41
η
2partial
= .07
p= .04
F
2,87
= 3.24
η
2partial
= .07
p= .04
Inclusion 4.57 ± .15 5.26 ± .15 5.16 ± .15
Ostracism 2.95 ± .21 3.15 ± .21 3.33 ± .21
Reflective stage 3.00 ± .23 3.66 ± .23 3.69 ± .23
RSA levels F
3,81
= .29
η
2partial
= .01
p= .84
F
2,83
= 9.87
η
2partial
= .19
p< .01
F
3,82
= 3.44
η
2partial
= .01
p= .02
Baseline 4.52 ± .27 5.54 ± .22 4.99 ± .26
Inclusion 3.98 ± .27 5.56 ± .22 4.94 ± .26
Ostracism 4.07 ± .26 5.61 ± .21 5.12 ± .25
Reflective stage 4.28 ± .24 5.83 ± .20 5.21 ± .23
BPD = patients with Borderline Personality Disorder; HC = Healthy Controls; rMDD = patients with Major Depressive Disorder in remission; NTS = Need Threat Scale;
RSA = Respiratory Sinus Arrhythmi a
Fig. 2 NTS scores (Panel A) and RSA levels (Panel B) across test conditions. Note: NTS = Need Threat Scale (higher scores represent greater
satisfaction with basic needs); RSA = Respiratory Sinus Arrhythmia. Error bars depict standard error. * = p< .05. In Panel A the satisfaction with basic
need (NTS, Y axis) across conditions (Inclusion, Ostracism and Reflective stage, X axis) in the three groups. After the Inclusion condition, BPD
patients experienced lesser satisfaction with basic needs than HC and rMDD. Furthermore, their level of satisfaction with basic needs did not
improve moving from the ostracism condition to the reflective stage. In Panel B Respiratory Sinus Arrhythmia (RSA, Y axis) across conditions
(Baseline, Inclusion, Ostracism and Reflective stage, X axis) in the three groups. RSA decreased from Baseline to Inclusion in BPD patients, but did
not vary in HC nor rMDD patients across the experimental conditions
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being included by others parallels a less efficient vagal
control during including social interactions. Notably, we
did not control this association for multiple
comparisons.
Discussion
The present study investigated whether BPD’s biased
perception of social interactions is associated with re-
duced physiological regulation, as indexed by impaired
vagal control, in response to experimental conditions of
social Inclusion and Ostracism. Three main findings
emerged.
Firstly, during the Cyberball task, individuals with
BPD subjectively reacted to inclusion with a higher per-
ception of threat to fundamental needs than healthy and
clinical controls. Furthermore, while in non-BPD con-
trols the fundamental needs were restored at the Reflect-
ive stage, patients with BPD did not show such recovery
from ostracism. Secondly, patients with BPD presented
lower resting RSA than HC, indicating stable difficulties
in social predisposition. Moreover, only in patients with
BPD, RSA further decreased in the inclusion condition
and remained low during Ostracism and the Reflective
stage. Finally, greater subjective perception of threats to
fundamental needs in the Inclusion condition was asso-
ciated with decreased RSA after being included, indicat-
ing that, during the Cyberball experiment, subjective
and physiological measures of perceived threats after be-
ing included paralleled each other.
At the subjective level, after being ostracized, as ex-
pected, all participants reported being threatened in
their fundamental needs [6]. However, only in the Inclu-
sion condition patients with BPD reported a weaker
sense of belongingness than did HC and patients with
rMDD. This indicates that patients with BPD do not
over-react to actual rejection, which is subjectively
threatening for everybody; instead, they emotionally
react to including interpersonal situations as they were
threatening. Although patients with BPD appeared cog-
nitively aware of the different degrees of threat conveyed
by Inclusion and Ostracism and correctly estimated the
percentage of ball tosses received during each condition,
they subjectively perceived a higher level of danger in
the including and accepting interaction than non-BPD
participants. This is in line with previous Cyberball stud-
ies showing that patients with BPD during the Inclusion
condition experienced a greater sense of exclusion and a
lesser sense of inclusion and belonging [8–11,57] and
reported lower feelings of social connection and greater
threats to their social needs than controls even when
over-included by others [11,12]. Thus, patients with
BPD show a biased subjective experience of social inclu-
sion during Cyberball [8,57].
Furthermore, in line with the Temporal Need-
Threat Model of ostracism [51], in this study,
threatened needs quickly recovered a few minutes
after Ostracism among both HC and rMDD. While
the detection of ostracism immediately generates
negative emotions, this in turn quickly motivates indi-
viduals to regulate their initial social pain in order to
access more positive emotions and restore functional
relations with others after Ostracism is over. Con-
versely, in this study patients with BPD did not re-
cover from Ostracism; rather, they kept reporting
feeling threatened in their need to belong. The ability
to recover faster and in more functional ways from
social exclusion has been found in individuals with
higher psychological flexibility levels. By contrast, a
delayed emotional recovery suggests difficulties in ac-
cess to, and use of, a wider range of emotion regula-
tion strategies to cope with ostracism experiences [58,
59]. For instance, socially anxious individuals exhibit
a slow recovery from the negative feelings induced by
ostracism [60].
This study also demonstrated that these explicit,
subjective findings parallel a corresponding pattern of
change in ANS reactivity at the implicit, physiological
level. BPD patients exhibited a lower RSA at baseline
than HC. Moreover, they also uniquely showed a fur-
ther decrease in RSA after the Cyberball Inclusion
condition –when they also reported, at the subjective
level, to be threatened (more than non-BPD controls)
in their need to belong.
Concerning baseline RSA, the present findings
confirm that patients with BPD show lower vagal
control at rest than HC [17–21]. This indicates that
even in the absence of interpersonal challenges (i.e.,
even before the Cyberball experiment), the BPD
group exhibits a physiological state of preparedness
for defensive rather than prosocial behaviors. Not-
ably, the finding of low RSA at rest in clinical popu-
lations, as compared to HC, is not limited to BPD
but also characterizes patients with anxiety disor-
ders, conduct disorders, autism spectrum disorders,
depression and schizophrenia (see for a review [61])
and, in this study, also patients with MDD in remis-
sion. This is not surprising given that patients with
diverse psychiatric disorders exhibit various degrees
of social dysfunction that are likely to be paralleled,
at the ANS level, by the inhibition of the social en-
gagement system when the vagal brake is removed.
This study extends these findings by indicating that
even after clinical remission patients with MDD
maintain a state of physiological arousal predispos-
ing to defensive rather than prosocial behaviors;
consistently, they also showed lower psychosocial
functioning than HC, as indexed by lower GAF
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scores, possibly as a “scar effect”of previous epi-
sodes. Thus, low RSA at rest, rather than being
disorder-specific, could represent a marker of the
difficulties in social behaviors shared by several psy-
chiatric disorders.
However, among HC and patients with rMDD, RSA
levels did not change from baseline across the three
Cyberball experimental conditions. This indicates that
they correctly appraised, at the physiological level, that
the task conveyed only minimal interpersonal stress
(Cyberball lasted about two minutes and involved two
unknown avatars online), but not greater threatening
risks. Thus, the experimental Cyberball conditions
employed in this study ultimately favored, among HC
and patients with rMDD, the maintenance of their vagal
regulation on the heart during and after the experiment.
Therefore, while at the subjective level both HC and pa-
tients with rMDD accurately perceived the Ostracism
condition as threatening their need to belong, they
maintained their capacity to regulate the vagal control
and then quickly recovered from their negative affective
states at the Reflective stage. On the contrary, patients
with BPD experienced a further drop in RSA after the
benign experimental condition of Inclusion. This vagal
withdrawal then persisted even at the reflective stage.
Thus, patients with BPD are not only biased to subject-
ively perceive rejection even in including contexts, or
when ostracism is over: they also implicitly appraise, at
the physiological level, such benign conditions as signal-
ing threats in the environment. This altered neurocep-
tion [13] of favorable social environments, in turn, leads
BPD patients to regulate their ANS to a state that would
support fight and flight responses but impedes social
flexibility and prosociality even after including interper-
sonal exchanges or when social interactions are over.
These findings are in keeping with other studies investi-
gating the potential neurophysiological bases of BPD
biased perception of rejection. For instance, during the
Cyberball Inclusion condition, patients with BPD show
an enhanced P3b event-related potential, which usually
signals social rejection [12,62] and hyper-activate the
“social pain”neural circuitry (i.e., the dorsal anterior cin-
gulate cortex and the dorsomedial prefrontal cortex)
[10]. These data suggest that patients with BPD process
objectively positive social interactions by activating
physiological and neural responses that signal rejection
and threat.
Finally, in this study, the subjective appraisal of threats
to one’s need to belong after the Inclusion condition
(NTS scores) directly correlated with the physiological
appraisal of the Inclusion condition as unsafe (decreased
RSA ratings after Inclusion), but not in any other stage
of the Cyberball task. This indicates that the tendency to
subjectively perceive including interpersonal interactions
as if they were excluding is underlined by a correspond-
ing altered physiological appraisal of such safe context
as if it was unsafe and risky. Such altered appraisal inev-
itably leads to the inappropriate activation of the ANS
defensive systems in an environment that is actually safe
and inhibits the prosocial responses fostered by the mye-
linated vagal regulation, which though would be re-
quired and adaptive in safe contexts [13].
Overall, these results point out to a “lowered ostracism
detection threshold”in BPD: when the threshold for de-
tecting signals of ostracism in the environment is set too
low, the ostracism detection system registers a high pro-
portion of false positives, interpreting benign (or even
mildly favorable) interpersonal events as potential
threats to acceptance [63]. Such interpretation is sup-
ported by converging lines of evidence indicating that
patients with BPD systematically underestimate positive
feedback from others. For instance, they show lesser ex-
pectations of being socially accepted than controls and
cannot adjust these expectations even after receiving ac-
tual positive feedback [64]. Furthermore, in behavioural
economics games, BPD under-notice others’fair behav-
iour toward them and react to that as if it was unfair by
punishing them [65]. Moreover, after experiencing actual
social acceptance, they behave less cooperatively toward
others [64]. Finally, individuals with BPD respond with
less positive emotions than controls to others’friendly
behaviour [66], and under-notice trust in others [67–69].
These findings are also consistent with clinical obser-
vations that patients with BPD do not seem to benefit
from benign, “fair”and accepting attitudes of others to-
ward them to regulate their emotional states, nor from
neutral interpersonal conditions where interpersonal re-
jection, although experienced in the past, is no longer
occurring. According to object-relations theory [70,71],
this response pattern may reflect the patient’s uncon-
scious idealized need of finding a perfectly “accepting”
relationship with others. However, this intense need is
unlikely to be fulfilled in reality, since human interac-
tions may also exhibit transient difficulties or ruptures
that are usually overcome by repairing trust and main-
taining reciprocity. For patients with BPD, though, such
less-than-perfect interpersonal interactions may not be
enough to fulfill their unconscious idealized need for
interpersonal belonging. Thus, in the desperate attempt
to protect this unconscious hope of a “perfect”relation-
ship, individuals with BPD need to project one’s negative
affect into the others; this makes them perceive includ-
ing social interactions as if they were unfair and exclud-
ing. This threatens the possibility to feel safe and
connected during “real”interpersonal exchanges.
Such dynamics could have significant implications for
treatment. Patients with BPD could feel easily threat-
ened, hurt and ignored even in the context of
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
therapeutic relationships, and may find it difficult to ap-
praise them as trustworthy, regardless of the objectively
cooperative stance of the therapist. This may affect the
therapeutic alliance and possibly evoke negative counter-
transference reactions in the clinicians, such as feelings
of frustration, inadequacy, and hopelessness. It is hence
important, for the clinician, to recognize that these feel-
ings in fact correspond to some aspects of their patients’
inner experience that they cannot tolerate. By maintain-
ing this empathic focus, the therapist can then explore
with the patients their perception to be threatened dur-
ing treatment and help them to appreciate that, although
the therapeutic relationship cannot provide a perfect or
magical solution to their problems, it can nonetheless
represent something of value to them. In the same vein,
the clinicians may encourage BPD patients to recognize
positive aspects in their real-life interpersonal relation-
ships by clarifying the defensive distortion of benign
interpersonal encounters as threatening. In turn, this will
favor the development of more gratifying and satisfac-
tory interpersonal relationships [72].
The results of this study should be interpreted in light
of some limitations.
First, our patients with BPD and rMDD exhibited
some socio-demographical differences, above all age.
This reflects the epidemiological distribution of BPD
and MDD. While BPD has an onset in adolescence or
early adulthood, and most patients experience symp-
tomatic remission in a few decades [73], MDD can
develop at any age, with a median age at onset at
30–40 years [74].
Moreover, we could not rule out the role of
pharmacotherapy on RSA levels, since both the clin-
ical groups kept their usual medication regimen, in
compliance with the Local Ethical Authority require-
ments and good clinical practice. Nonetheless, in this
study, patients with (N= 43) and without (N=17) an-
tidepressants did not differ in baseline RSA (F
1.51
=
.38, p=.54, η2
partial
= .01), regardless of their clinical
group status. Moreover, in our analyses, we controlled
for other physiological variables that have previously
been demonstrated to affect RSA (i.e., age, BMI, alco-
hol and tobacco consumption) [75–78].
Furthermore, while in the present study healthy and
clinical controls subjectively perceived the ostracism
condition as potentially threatening (thereby confirming
the widely-replicated validity of the Cyberball experi-
mental manipulation), at the physiological level they did
not exhibit a parallel withdrawal in RSA. This is likely
due to the successful recruitment of self-regulatory abil-
ities in HC and in patients with rMDD, which favored
the appraisal, at the physiological level, of the Cyberball
ostracism condition as a minimal and transient interper-
sonal stress, and therefore the maintenance of vagal
control. This was not the case for patients with BPD,
who are known to react with increasing distress to any
situation where rejection is a possibility (in the present
study, to the Cyberball social inclusion condition) be-
cause of their self-regulation difficulties [79,80]. A sub-
sequent vagal suppression did not occur from inclusion
to ostracism, among patients with BPD, because it was
already withdrawn from baseline to inclusion, and RSA
reactivity scores could be susceptible to a floor effect of
functional adaptations [81].
Finally, in our study, we interpreted RSA in the Poly-
vagal Theory framework, which posits that RSA suppres-
sion is associated with the neurophysiological appraisal
of the environment as dangerous, thus leading to defen-
sive, rather than pro-social behaviors. However, contra-
dictory findings have been reported regarding RSA
changes in response to varying environmental cues [82]
and some researchers suggested that the evolution of the
parasympathetic ANS has a greater anatomical and
physiological complexity than what was proposed by the
Polyvagal Theory [16,83]. Therefore, the specificity of
RSA as a physiological marker of BPD patients’biased
perception of social participation needs to be confirmed
by further research.
Conclusions
The results of this study indicate that patients with BPD
perceive (at the subjective level) threats to their need to
belong during accepting social encounters, as well as
when the experience of ostracism is no longer present.
They also appraise (at the implicit, physiological level)
such circumstances as threatening and dangerous,
thereby showing an autonomic response characterized
by increased physiological arousal and proneness to de-
fensive reactions and breakdown in prosocial behavior.
These findings support the view that patients with BPD
appraise and react, both subjectively and physiologically,
to positive social contexts as if they were unsafe and
rejecting. This prevents them from appreciating and re-
ciprocating objectively inclusive, “fair”social exchanges.
Thus, individuals with BPD may benefit from interven-
tions that help them to accurately appraise positive cues
in their social and interpersonal interactions.
Abbreviations
ANOVA: analyses of variance; ANS: Autonomic Nervous System; BMI: Body
Mass Index; BPD: Borderline Personality Disorder; ECG: Electrocardiogram;
GAF: Global Assessment of Functioning; HAM-A: Hamilton Anxiety Rating
Scale; HAM-D: Hamilton Rating Scale for Depression; HC: Healthy Controls;
NTS: Need-Threat Scale; rMDD: remitted Major Depressive Disorder;
RSA: Respiratory Sinus Arrhythmia; SCID-5-PD: Structured Clinical Interview for
DSM-5 Personality Disorders; SCID5-CV: Structured Clinical Interview for DSM-
5 disorders, Clinician Version
Acknowledgements
Not applicable.
Gerra et al. Borderline Personality Disorder and Emotion Dysregulation (2021) 8:28 Page 11 of 14
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Authors’contributions
Authors MLG, MA, PR, EP, BM, CDP, and VG designed the study. Authors
MLG, MA, SM, VL, PR; EP and CDP managed the literature searches. Authors
MLG, SM and VL recruited the participants. Authors MLG, MA, SM and PO
undertook the statistical analysis. Authors MLG, MA and CDP wrote the first
draft of the manuscript. MLG, MA, SM, VL, CDP, PR, EP, PO, CM and VG
interpreted the results. All authors contributed to and have approved the
final manuscript.
Funding
This work was supported by Paola Chiesi and by a PRIN grant on Perception,
Performativity and the Cognitive Sciences to VG.
Availability of data and materials
The dataset analyzed during the current study is available from the
corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Participants gave written informed consent to participation and, after
completion of the experiment, were extensively debriefed and given
detailed information about the study and its purposes, with the opportunity
to have their data deleted should they wish so. Participants were not
reimbursed for their participation. The Local Ethical Authority (Comitato Etico
Unico per Parma, protocol #6266 01/29/2016) approved the study protocol.
All procedures contributing to this work comply with the relevant national
and international committees’ethical standards on human experimentation
and with the Helsinki Declaration of 1972, as revised in 2013.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Department of Mental Health, AUSL of Parma, Parma, Italy.
2
Department of
Medicine and Surgery, University of Parma, Parma, Italy.
3
Department of
Psychology, University of Milano-Bicocca, Milan, Italy.
Received: 15 August 2021 Accepted: 20 October 2021
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