Journal of Affective Disorders Reports 16 (2024) 100726

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Journal of Affective Disorders Reports

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Research Paper

Validity of PDQ4+ self-screening to assess the impact of personality

disorder traits on the course of bipolar disorder
Georg Riemann a, b, *, Marjolein Apenhorst-Hol c, Nadine Weisscher d, Melissa Chrispijn e, Ralph
W. Kupka f
a
Fontys University of Applied Science, Emmasingel 28, 5611 AZ Eindhoven, the Netherlands
b
Dimence Mental Health, Center for Bipolar Disorders, Deventer, the Netherlands
c
Medisch Spectrum Twente, Department of Medical Psychology, the Netherlands
d
GGZ Heuvelrug, Center for Mental Health, Driebergen, the Netherlands
e
Dimence Mental Health, Deventer, the Netherlands
f
Amsterdam University Medical Center, Location Vrije Universiteit, Department of Psychiatry, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Patients with bipolar disorder (BD) and comorbid personality disorder (PD) have a less favorable
Bipolar disorder illness course than those without comorbidity. They are more difficult to stabilize and make more use of mental
Personality disorder traits health care. This may also be true for PD traits that do not meet criteria for a specific PD. The aim of this study is
Comorbidity
to investigate whether a simple self-screening instrument (PDQ-4+) can provide an indication of expected
Illness severity
severity and course of BD.
Methods: Patients completed the PDQ-4+ and the treating clinician independently assessed retrospectively over
the past 12 months the course of BD (number of depressive and (hypo)manic episodes, number and duration of
hospitalizations, and suicide attempts) and the overall severity of illness using the Clinical Global Impression
scale for BP (CGI-BP). Mann-Whitney U tests were used for group comparisons. Spearman rho was used to
evaluate associations between the prevalence of PD traits and course of BD.
Results: The prevalence of a positive PD screening in the sample with BD was 57.5 %. Patients who screened
positive on specific PD were on average rated as more severely ill. More importantly, the total number of all
dysfunctional personality traits was associated with less favorable course of BD and had a higher validity than
any individual PDs. A limitation of our study is the small sample size and retrospective assessment of BD course.
Conclusion: Screening with PDQ-4+ helps to identify a group at risk for a more severe illness course of BD. More
important than meeting formal criteria for any PD are the accumulation of dysfunctional personality traits in
patients with BD.

1. Background clinicians. One of these factors is the presence of comorbid personality

Bipolar disorder (BD) is one of the most costly psychiatric disorders
according to the World Health Organization (WHO) (Murray and Lopez,
1997). Although many pharmacological and psychological treatments
have proven efficacy, longitudinal studies show that, despite of
state-of-the-art treatment, episodes often recur, residual symptoms
persist, and cognitive and functional impairment is common (Dunaye­
vich et al., 2000; Bieling et al., 2007). Therefore, factors that may have
impact on symptom severity and illness course are of special interest for
disorder (PD) (Dunayevich et al., 2000; Bieling et al., 2007). The prev­
alence of comorbid PD in patients with BD is estimated between 30 and
40 % (Kay et al., 2002; George et al., 2003; Schiavone et al., 2004;
Garno et al., 2005; Friborg et al., 2014), mostly in the so-called cluster B
and cluster C. Although defining illness severity in BD is complex since it
is determined by a combination of symptom severity, duration, and
frequency of both (hypo)manic and depressive episodes (Spearing et al.,
1997), the presence of comorbid PD has been associated with a more
severe illness course and less treatment responsivity (Kay et al., 1999;

Abbreviations: BD, bipolar disorder; CGI-BP, clinical global impression–version bipolar disorder; PD, personality disorder; PDQ-4+, personality diagnostic
questionnaire-4; STEPPS, systems training for emotional predictability and problem solving.
* Corresponding author at: Fontys University of Applied Science, Emmasingel 28, 5611 AZ Eindhoven, the Netherlands.
E-mail address: g.riemann@fontys.nl (G. Riemann).

https://doi.org/10.1016/j.jadr.2024.100726
Received 13 September 2023; Received in revised form 2 December 2023; Accepted 8 January 2024
Available online 10 January 2024
2666-9153/© 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
G. Riemann et al.
Carpenter et al., 1995; Crawford et al., 2008; Kay et al., 2002; Kutcher
et al., 1990). Studies show that patients with BD and comorbid PD are
more likely to be hospitalized, require more time to achieve symptom
remission if this is reached at all, have higher levels of suicidality, are
less compliant to pharmacotherapy, and make more use of mental health
care services (Bieling et al., 2007). In addition to the finding that co­
morbidity of PD is associated with poorer outcome on the overall course
of BD, it is of interest to investigate the impact on symptom severity. A
systematic review concluded that comorbidity with personality disor­
ders in BD patients is associated with a less favorable course of illness
(such as longer episodes, shorter time euthymic, and earlier age at onset)
and an increase in comorbid substance abuse, suicidality, and aggres­
sion. These problems are particularly pronounced in comorbidity with
borderline personality disorder (Latalova et al., 2013). Given the over­
lap in clinical presentation with BD, borderline PD is of special research
interest. Some authors (Latalova et al., 2013) have even suggested that
BD and borderline PD are part of a continuum within one spectrum,
while others consider these as discrete entities (Akiskal, 1994; Paris,
2004). DSM-5 (APA 2013) makes a clear distinction between BD and
borderline PD, although especially BD rapid cycling may be difficult to
differentiate from borderline PD (Mackinnon and Pies, 2006), and
having borderline PD increases the risk of being misdiagnosed with BD
(Ruggero et al., 2010). In clinical practice, this overlap causes both
diagnostic difficulties and treatment challenges.
Our current study focuses on the impact of all PD features as assessed
with the Personality Disorder Questionnaire-4+ (PDQ-4+) (Hyler,
1994) on illness severity and course in BD. Since a formal diagnosis of
PD can be time consuming and expensive, and thus not feasible in
routine clinical practice, this study aims to identify a potential more
vulnerable patient group by using an efficient self-report questionnaire
for personality disorders (PDQ-4+). Several studies have compared the
PDQ-4+ with semi-structured interviews and have found a tendency to
overdiagnose PD (de Reus et al., 2013). Although this may lead to
caution in using the PDQ-4+ for a formal diagnosis of PD, it may be
useful for detecting subthreshold PD traits. Most research in this area
dismissed the impact of PD traits, since patients not meeting full
DSM-criteria for PD will be included in a no-PD group. However, it is
likely that also subthreshold PD’s, or a mix of various dysfunctional
personality traits even beyond the ‘clusters’, will influence outcome on
course and symptom severity in BD (Bieling et al., 2007).
In order to evaluate whether the PDQ-4+ is a useful tool to identify
patients with either threshold or subthreshold comorbid PD at risk for
poor outcome in BD, the aims of this study are: (1) to determine the
prevalence of screening positive for PD in patients with BD, (2) to
examine the association of screening positive for PD and PD traits with
the overall course of the BD retrospectively assessed for the past year.
We hypothesized that screening positive for PD would be highly
prevalent in this sample, that screening positive for PD measured by
PDQ-4+ can be associated with a less favorable course of BD defined by
the adapted CGI-BP score and overall illness course over the past year.
This may especially be true for comorbid borderline PD (traits) given the
overlapping features of BD and borderline PD. Due to the objectives of
the present study, only the results of the PDQ-4+ have been included in
the analyses. Other potentially important factors that could also have an
influence on the outcome of BD were not considered.
2. Methods
2.1. Sample and procedure
Participants were patients aged 18–65 years who were at the time of
inclusion receiving treatment in a specialized outpatient clinic for BD in
the Netherlands consisting of guideline-recommended pharmaco­
therapy, psychoeducation and supportive counseling. All participants
met the DSM-5 (APA, 2013) criteria for BD-I, BD-II, or BD-NOS, as
evaluated by their treating psychiatrist and received treatment for BD at
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Journal of Affective Disorders Reports 16 (2024) 100726
the time of evaluation. The diagnostic process was performed according
to the Dutch Guideline for Bipolar Disorders (Kupka et al., 2015) and
included a full psychiatric examination, which consisted of a thorough
evaluation of the past mood episodes and their precipitating factors
using retrospective life charts, and a family history of mood disorders
and suicides. A history was also taken by the person(s) close to the pa­
tient to verify or enrich the psychiatric examination. Furthermore, the
medication history and psychiatric and somatic comorbidity were
assessed. Patients were informed about the study by their treating
clinician. Patients who were interested to participate were referred to
the investigators and received both written and oral information about
the study. After signing informed consent participants completed the
PDQ-4+, Dutch translation (Akkerhuis et al., 1996) in digital form or in
writing. Given the aims of this study, which investigated the value of PD
screening, patients did not receive an additional formal diagnostic
interview for PD. All patients had been treated for BD for at least one
year at time of inclusion. Patients who were not closely followed by their
treating clinician for the past year were excluded. Patients without
sufficient understanding of the Dutch language were excluded.
Being unaware of the results of the patient-completed PDQ-4+, the
treating clinicians answered questions about the course and severity of
the BD over the past 12 months of every individual patient, based on the
clinical records. To further enhance the accuracy of this retrospective
assessment, the clinicians were first asked to answer questions about the
frequency of clinical symptoms and illness course related to BD in the
past year. Next, they were asked to give a global score of the overall
severity of BD one year retrospectively on a modified version of the CGI-
BP part I, severity (7-point Likert scale).
This study was a post-hoc analysis of data gathered as part of a larger
study (Riemann et al., 2014) that was reviewed and approved by the
clinic’s scientific ethics committee and by the ethics committee of the
VU University Medical Center, Amsterdam, The Netherlands. Prior to
participation patients signed an informed consent form.
2.2. Measures
2.2.1. Screening for personality disorder
The presence of various DSM-5-defined PDs was assessed using the
PDQ-4+ (Akkerhuis et al., 1996). This is a 99-item self-report ques­
tionnaire in which patients answer ‘true’ or ‘false’ to a series of questions
that reflect the diagnostic criteria of the DSM-5 PDs, and in addition
depressive PD and passive-aggressive PD that are not included in
DSM-IV and DSM-5. Each item on the PDQ-4+ questionnaire precisely
reflects a single DSM-5 diagnostic criterion, and sufficient positive an­
swers, as defined by DSM-5 results in a positive screening of the corre­
sponding PD.
2.2.2. Retrospective illness course and severity of bipolar disorder
symptoms
Based on medical records for every individual patient, the treating
clinician retrospectively recorded the following determinants of the
course of BD in the previous 12 months: the number of depressive and
hypomanic/manic episodes, the number of hospitalizations (0; 1; 2; 3; 4;
5–10; 11–20; or >20) for either a manic or a depressive episode, total
weeks of hospitalization, and the number of suicide attempts.
Next, considering these clinical characteristics, the overall severity of
BD in the past year was scored by the same clinician with a modified
version of the CGI-BP. To address the complexity of BD illness course,
the original CGI-BP was designed to globally assess the severity of
manic, depressive, and overall BD symptoms over the past week
(Spearing et al., 1997). Our modified version of the CGI-BP allows cli­
nicians to integrate the severity, duration and frequency of episodes, and
functional impairment as a consequence of BD in one overall global
score over the past 12 months. Clinicians received the following in­
struction: “Considering your total clinical experience with BD patients,
how severely ill has your patient been during the past year? Rate the
G. Riemann et al. Journal of Affective Disorders Reports 16 (2024) 100726

severity of illness due to BD including manic and depressive symptoms one or more PDs were common (57.5 % screened positive for at least one
and functional impairments”. Clinicians rated the severity of BD one PD) with avoidant PD, borderline PD, and depressive PD as the most
year retrospectively on a 7-point Likert scale with score 1 (normal not prevalent. 42.5 % did not screen positive for any PD. Least prevalent
ill) to 7 (very severely ill), integrating manic and depressive symptom­ were antisocial PD, histrionic PD, and passively aggressive PD.
atology. A short description for each score identical to the original
CGI-BP was given, e.g. “No discomfort, bipolar symptoms, or functional 3.2. Illness severity of BD in patients with and without screening positive
limitations” in case of “normal not ill”, or “Severe symptoms, patient is for PD
unable to function and requires a high level of care” in case of “very
severely ill”. When assessing severity and course of BD, clinicians were The mean score of the CGI-BP part I overall (N = 40) was 3.30 (SD
unaware of the results on the PDQ-4+ as scored by the patient. 1,59). No significant gender difference was found (U = 151,5; Z =
− 1047 p = 0,29) between the groups. The CGI-BP Part I score was sta­
2.3. Statistical methods tistically significantly higher in the group screening positive for PD than
in the group screening negative for the following PD’s: schizotypal (U =
Data were analyzed using SPSS for Windows (version, 26). Descrip­ 72,5, Z = − 2743 p = 0,01), borderline (U = 103; Z = − 0.2,179 p = 0,29),
tive statistics included means (M) and standard deviations (SD) for narcissistic (U = 26,5; Z = − 2135 p = 0,33), histrionic (U = 12; Z =
continuous variables, median (m) and mean rank score for ordinal var­ − 2325 p = 0,02), and depressive (U = 110; Z = − 2356 p = 0,18).
iables and percent’s for categorical variables. We compared overall Screening positive for multiple PD’s was likely in our sample. Only five
illness course in patients with and without a positive score on all patients screened positive for only one PD. Of the patients with at least
different PD sections. In addition, we analysed whether there was an one PD, on average at least three other PDs (mean 4.04 total PD’s) were
association between the overall number of positive personality trait also present. Table 2 shows results of all Mann-Whitney U test
scores (PDQ-4+ total score) and the course of BD. Because the total score comparing CGI-BP scores between groups with and without respective
on the CGI-BP was not normally distributed and the scaling of the PD screening on PDQ-4+. It should be mentioned that only four patients
questions considering the course of BD was ordinal, Mann-Whitney U positively screened for narcissistic PD and only three for histrionic PD.
tests (two-tailed) were used for group comparisons. In order to analyse The group that was screened positive for at least one PD (any PD) had
the correlation between BD severity and the number of positive screened higher scores on CGI-BP than the group without any positive screening
personality traits Spearman’s rho was used. PD (no PD), but the difference did not reach significance. In addition to
the analysis of differentiation, a Spearman-Rho correlation analysis of
3. Results the PDQ-4+ total score with the CGI-BP score was also performed. The
total PDQ-4+ score was calculated by adding all positive items. Results
3.1. Demographics and prevalence of PD showed that he PDQ total score was also positively correlated with CGI-
BP score (rs = 0.43 p < 0.05).
Of 78 patients that were approached to participate in the study, 58
returned a valid PDQ-4+ measurement. In 40 of these 58 patients, 3.3. Course of BD in relationship to number of positive screened PD’s
treating clinicians completed the CGI-BP and the additional six ques­
tions about illness course. Table 1 shows the demographic and clinical The course of BD was assessed by six additional questions concerning
characteristics of the patients who completed the PDQ-4+ and of whom the number of (hypo)manic or depressive episodes, the number of hos­
CGI-BP data were also available (n = 40). Of these 40 patients, 19 had no pitalizations due to (hypo)manic or depressive episodes, the duration of
(hypo)manic nor depressive episodes in the past year. Positive scores on hospitalization and suicide attempts. There were no suicide attempts
reported during the past year in the whole sample. The results of the
Table 1
correlation of all course variables and the number of positive screened
Demographic and clinical characteristics of the total sample of patients with BD PD’s as well as the number of positive screened personality traits are
(N = 40). presented in Fig. 1.
Age (SD) 48.4 (12.2)
Female (%) 25 (62.5) 4. Discussion
BD Diagnosis (%)
BD-I 22 (55) In this study, we found that in a sample of outpatients with BD, a
BD-II 17 (42.5) higher number of maladaptive personality traits, identified with the
BD-NOS 1 (2.5)
Course of BD in past year (%)
PDQ-4+ self-rated screening tool, was associated with an unfavorable
patients without any mood episode 19 (47.5) course of BD. Since several studies have shown that the comorbidity of
patients with only(hypo)manic episodes 2 (5) BD and borderline PD lead to a worse course of illness (Latalova et al.,
patients with only depressive episodes 9 (22.5) 2013; Zimmerman et al., 2021; Zimmerman et al., 2014; Swartz et al.,
patients with both (hypo)manic and depressive episodes 10 (25)
2005), we assumed that especially borderline PD has a good prognostic
patients hospitalized for mood episodes 4 (10)
patients with suicide attempts 0 value for an unfavorable course of BD, but this assumption could not be
Screening positive for personality disorder on PDQ-4+ (%) confirmed by this study using the screening instrument PDQ-4+ for PD.
Paranoid 5 (12.5) We found that in patients with schizotypal, borderline, narcissistic,
Schizotypal 11 (27.5) histrionic, and/or depressive PD features, the course of BD in the past
Schizoid 5 (12.5)
Borderline 13 (32.5)
year measured by total score on a modified CGI-BP scale was worse than
Narcissistic 4 (10) in patients without these features. It is important to realize that these
Antisocial 1 (2.5) patients also screened positive for multiple other PDs (see Table 2). It is
Histrionic 3 (7.5) therefore not possible to assess the impact of any single PD on the course
Avoidant 17 (42.5)
of BD. Our results showed that it was primarily the sum of all dysfunc­
Dependent 7 (17.5)
Obsessive compulsive 8 (20) tional personality traits, beyond a specific PD or ‘cluster’, that correlated
Depressive 16 (40) best with the overall illness course in the previous year.
Passive-aggressive 3 (7.5) Further correlation analyses showed that the total number of PD
Any PD 23 (57.5) traits was associated with the number of (hypo)manic and depressive
No PD 17 (42.5)
episodes, the number of hospitalizations for mood disorders, as well as

3
G. Riemann et al. Journal of Affective Disorders Reports 16 (2024) 100726

Table 2
Group differences from Mann-Whitney U test of CGI-BP scores between group with and group without screening positive on different PD’s in n = 40 patients with BD. In
addition, the second column shows how many other PDs screened positive.
PD screening screening positive on other CGI-BP median (mean screening CGI-BP median (mean U (p two-
positive PD’s rank) negative rank) tailed)
N mean N

Paranoid 5 7.2 4 (26.3) 35 3 (19.67) 58.5 (0.22)

Schizotypal 11 5.5 4 (28.41) 29 2 (17.5) 72.5 (0.01)*
Schizoid 5 5.4 4 (26.1) 35 3 (19.7) 59.5 (0.23)
Borderline 13 5.6 4 (26,08) 27 2 (17.81) 103 (0.03)*
Narcissistic 4 8.25 5 (31.88) 36 2.5 (19.24) 26.5 (0.03)*
Antisocial 1 10 5 (33.5) 39 3 (20.17) 6.5 (0.24)
Histrionic 3 7.67 5 (35) 37 3 (19.32) 12 (0.02)*
Avoidant 17 4.71 4 (23.82) 23 2 (18.04) 139 (0.11)
Dependent 7 5.43 4 (23.57) 33 3 (19.85) 94 (0.43)
Obsessive 8 5.63 3.5 (24.5) 32 2.5 (19.5) 96 (0.26)
compulsive
Depressive** 16 5 4 (25.63) 24 2 (17.08) 110 (0.02)*
Passive-aggressive** 3 9 5 (31.33) 37 3 (19.62) 23 (0.08)
Any PD 23 4.04 3 (22.02) 17 2 (18.44) 160.5 (0.32)
*
significant on 0.05 level.
**
part of the PDQ-4+ (not included in DSM-5).

Fig. 1. Spearman Rho between total CGI-BD score and five different course variables in correlation with number of positive screened personality traits.

the duration of these hospitalizations, and reached significance for respond to naturalistic treatment compared with patients without PD
depressive episodes and hospitalizations for depression. (Post et al., 2020). The prevalence of PD as screened with PDQ-4+ in our
Our results confirm other studies reporting that patients with BD and sample was 57.5 %, but it must be taken into account that the PDQ-4+ is
comorbid PD had a less favorable illness course and were less likely to a sensitive instrument which has a tendency to overdiagnose PDs (de

4
G. Riemann et al.
Reus et al., 2013). Therefore it cannot be stated that patients with a
positive score do have a PD according to strict DSM-5 criteria, but
instead may have only subthreshold traits of PD. If so, our findings
suggest that even traits of PD may be associated with an unfavorable
course of BD, and that the item-total score of the PDQ-4+ is a useful
measure to identify patients at risk for an unfavorable course of BD.
Interestingly, the sum of all dysfunctional personality traits across the
clusters may be more relevant than a formal diagnosis of any specific PD,
including borderline PD.
The results of our study have relevance for clinical practice. Using an
easy to administer screening instrument, even with a relatively small
number of participants we found an association between dysfunctional
personality traits and an unfavorable course of BD. By administering the
PDQ-4+ early in treatment, a possible extra vulnerable group of patients
could be identified. Being aware of this could influence treatment
planning, e.g., the timely addition of psychological interventions that
reach beyond the symptomatology of BD as such, even in the absence of
a full-blown PD.
Studies on a combined treatment of BD patients with comorbid PDs
are still scarce, with some exception of borderline PD. Given the over­
lapping features of BD and borderline PD, especially the significant
impairment of emotion regulation strategies in comorbid BD and
borderline PD (Bayes et al., 2016), as well as the characteristic
emotional instability of BD, it can be hypothesized that psychological
interventions that have a positive impact on these symptoms will miti­
gate the illness course of the comorbid patient population of BD and
borderline PD. Recent studies indicate that Systems Training for
Emotional Predictability and Problem Solving (STEPPS) (Blum et al.,
2002) has a positive effect on clinical symptoms in patients with
borderline personality features. Pre-post treatment comparison of a pilot
study in 21 adolescents with emotional instability showed an improve­
ment especially in affective symptoms (Llorens Ruiz et al., 2020).
Another feasibility study showed that in patients with a BD diagnosis
and comorbid borderline personality features, several clinical parame­
ters as well as quality of life improved (Riemann et al., 2021).
Our study has several limitations. The small sample size may have
affected the statistical analyses. For example, only four patients were
hospitalized in our sample. This limits the variance of the correlative
analysis between number/duration of hospitalizations and PD. A small
number of cases that occurred by chance can affect the interpretation of
the distribution of the cases, and thus the statistical analysis may not
reflect the real situation.
It should also be mentioned that only 51.3 % of invited patients in the
larger study (Riemann et al., 2014) participated in this part of the study,
since not all patients completed the PDQ-4+ and not all treating clini­
cians completed the CGI-BD. Since the reasons were not systematically
assessed it was not possible to determine whether there was selective
drop-out, which may lead to a restriction of variance.
We acknowledge the tendency of PDQ-4+ to overdiagnose PDs, but
this may also be regarded as useful, as we have explained. Our study
used the retrospective rather than a prospective course of illness, with
personality traits assessed at the end of the year of investigation. It may
therefore be possible that the previous course of illness may have
influenced the PDQ-4+ scoring by the patient, and it is therefore not
possible to firmly state that dysfunctional personality traits are a risk
factor or a consequence for a worse course of BD. We used a non-
validated modified version of the CGI-BD, extending the retrospective
time frame from one week to one year, giving detailed instructions to
clinicians how to score.
Participants were recruited from an outpatient clinic for BD. All
participants met DSM-5 (APA, 2013) criteria for BD-I, BD-II, or BD-NOS
as assessed by to their treating psychiatrist following Dutch guidelines
(Kupka et al., 2015) and were currently being treated for BD. The
diagnosis of BD was not re-assessed for this study by semi-structured
interviews, which may have had consequences for diagnostic accuracy
of BD.
5
Journal of Affective Disorders Reports 16 (2024) 100726
Another limitation was that we only included the PDQ-4+ screening
data in the analyses. Important factors that may also have an impact on
the outcome of BD were not taken into account. This includes de­
mographic variables such as education, socio-economic status, family
history, but also psychological variables such as substance misuse,
alcohol dependence, forensic history and medical adherence.
In conclusion, using a simple self-administered screening tool for
personality disorders can detect patients with BD and multiple
dysfunctional personality traits not restricted to any specific PD or PD
cluster who may have a relatively unfavorable course of illness and may
be in need for additional psychological interventions beyond the usual
recommendations in treatment guidelines for bipolar disorder.
Ethics approval
This study was a post-hoc analysis of data gathered as part of a larger
study that was reviewed and approved by the clinic’s scientific ethics
committee and by the ethics committee of the VU University Medical
Center, Amsterdam, The Netherlands. Prior to participation patients
signed an informed consent form.
Consent for publication
Consent to publish has been obtained from all participants.
Availability of data and materials
The dataset used and/or analyzed during the current study are
available from the corresponding author on reasonable request.
Funding/support
This research was supported by the Netherlands Organization for
Scientific Research (NWO).
PO Box 93138, NL-2509 AC The Hague; The Netherlands, phone +31
(0)70 344 06 40; fax+31 (0)70 385 09 71, general e-mail address:
nwo@nwo.nl.
CRediT authorship contribution statement
Georg Riemann: Conceptualization, Data curation, Formal analysis,
Funding acquisition, Writing – original draft, Writing – review & editing.
Marjolein Apenhorst-Hol: Conceptualization, Data curation, Writing –
original draft, Writing – review & editing. Nadine Weisscher:
Conceptualization, Supervision, Writing – original draft, Writing – re­
view & editing. Melissa Chrispijn: Conceptualization, Supervision,
Writing – original draft, Writing – review & editing. Ralph W. Kupka:
Conceptualization, Funding acquisition, Supervision, Writing – original
draft, Writing – review & editing.
Declaration of competing interest
The authors declare that they have no conflict of interest.
Acknowledgments
Not applicable.
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