Available via license: CC BY 4.0
Content may be subject to copyright.
Medicina 2021, 57, 183. https://doi.org/10.3390/medicina57020183 www.mdpi.com/journal/medicina
Review
Antisocial Personality Disorder in Bipolar Disorder: A System-
atic Review
Elvira Anna Carbone
†
, Renato de Filippis
†
, Mariarita Caroleo
†
, Giuseppina Calabrò, Filippo Antonio Staltari,
Laura Destefano, Raffaele Gaetano, Luca Steardo Jr.
†
, Pasquale De Fazio *
Department of Health Sciences, University Magna Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy;
elvira.carbone@libero.it (E.A.C.); defilippisrenato@gmail.com (R.d.F.); mariaritacaroleo.82@gmail.com (M.C.);
giusy878@gmail.com (G.C.); filippostaltari89@gmail.com (F.A.S.); lds@laradestefano.com (L.D.); rafgae74@li-
bero.it (R.G.); staerdo@unicz.it (L.S.J.)
* Correspondence: defazio@unicz.it; Tel/Fax: +39-0961-712369
† These authors contributed equally to this work.
Abstract: Background and Objectives: Bipolar Disorder (BD) is a severe psychiatric disorder that wors-
ens quality of life and functional impairment. Personality disorders (PDs), in particular Cluster B
personality, have a high incidence among BD patients and is considered a poor prognostic factor.
The study of this co-morbidity represents an important clinical and diagnostic challenge in psychi-
atry. Particularly, clinical overlap has been shown between antisocial personality disorder (ASPD)
and BD that could worsen the course of both disorders. We aimed to detect the frequency of ASPD
in bipolar patients with greater accuracy and the impact of ASPD on the clinical course of BD. Ma-
terials and Methods: A systematic literature search was conducted in PubMed, Embase, MEDLINE
and the Cochrane Library through December 2020 without language or time restriction, according
to PRISMA statement guidelines. Results: Initially, 3203 items were identified. After duplicates or
irrelevant paper deletion, 17 studies met the inclusion criteria and were included in this review.
ASPD was more frequent among BD patients, especially in BD type I. BD patients with ASPD as a
comorbidity seemed to have early onset, higher number and more severe affective episodes, higher
levels of aggressive and impulsive behaviors, suicidality and poor clinical outcome. ASPD symp-
toms in BD seem to be associated with a frequent comorbidity with addictive disorders (cocaine
and alcohol) and criminal behaviors, probably due to a shared impulsivity core feature. Conclusions:
Considering the shared symptoms such as impulsive and dangerous behaviors, in patients with
only one disease, misdiagnosis is a common phenomenon due to the overlapping symptoms of
ASPD and BD. It may be useful to recognize the co-occurrence of the disorders and better charac-
terize the patient with ASPD and BD evaluating all dysfunctional aspects and their influence on
core symptoms.
Keywords: bipolar disorder (BD); antisocial personality disorder (ASPD); comorbidity; substance
abuse; outcome; systematic review
1. Introduction
Bipolar Disorder (BD) is a chronic affective disorder characterized by mood fluctua-
tions with recurrent cycles of mania in BD I, or hypomania in BD II, and depression epi-
sodes [1,2], with a highly variable course among patients. The lifetime prevalence of BD
is estimated to be around 2–3% in the general population [3] and sub-threshold forms
affect at least a further 2% [4]. BD is characterized by a worsening in quality of life [5] and
functional impairment [6,7] and is frequently associated with other psychiatric comorbid-
ities that could lead to a worse outcome [8–15]. It has been estimated that patients with
BD are exposed to a second psychiatric disorder with longitudinal rates that can be higher
than 50% and may reach even 70% [16]. The most common mental disorders that co-occur
Citation: Carbone
,
E.A.; de Filippis
,
R.; Caoleo, M.; Calabrò, G.; Staltari,
F.A.; Destefano, L.; Gaetano, R.;
Steardo, L., Jr.; DeFazio, P.
Antisocial Personality in Bipolar
Disorder: A Systematic Review. Me-
dicina 2021, 57, 183. https://doi.org/
10.3390/medicina57020183
Academic Editor: Woojae Myung
Received: 8 January 2021
Accepted: 15 February 2021
Published: 20 February 2021
Publisher’s Note: MDPI stays neu-
tral with regard to jurisdictional
claims in published maps and institu-
tional affiliations.
Copyright: © 2021 by the authors. Li-
censee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and con-
ditions of the Creative Commons At-
tribution (CC BY) license (http://crea-
tivecommons.org/licenses/by/4.0/).
Medicina 2021, 57, 183 2 of 17
with BD are drug abuse (33.5%), anxiety disorders (31.8%), alcohol abuse (18.3%), obses-
sive-compulsive disorder (OCD) (21%), eating disorders (33%), attention deficit hyperac-
tivity disorder (ADHD) (25%), and post-traumatic stress disorder (PTSD) (from 4 to 40%)
[17–23]. In addition, particularly high is the incidences of cluster B personality disorders
in BD that are estimated at 41.2% even in the euthymic phase [24] and, represent a poor
prognostic factor [25–28]. The study of this co-morbidity represents an important clinical
and diagnostic challenge in psychiatry. Furthermore, Cluster B personality disorders have
several common features with BD such as impulsivity, aggressive behavior, and mood
instability, enough to induce some authors to consider them part of the bipolar spectrum
[29]. Instead, features associated with Cluster B personality disorders may be a dimen-
sional aspect of BD, and when combined could result in greater complexity and severity
of the disease [30,31]. Conversely, the presence of BD could worsen the course of a per-
sonality disorder [32]. Several studies have shown that the presence of cluster B personal-
ity in BD is associ ated wi th a hig her number of episodes, substance abuse, illegal behavior,
a higher rate of suicide risk, and a poor treatment adherence [32–34]. In this scenario, re-
searchers have focused on the impact of personality disorder on BD, investigating the
common traits that mutually lead to a worse outcome [34]. Particularly, the clinical over-
lap has been shown between antisocial personality disorder (ASPD) and BD.
According to the DSM-5, the ASPD is described as the existence of constant and per-
vasive disposition to disregard and disrupt the rights of others. Other specific features
include frequent violations of the law, mistreatment of others, deceitfulness, impulsivity,
hostility, reckless disregard for the safety of self and others, and imprudent behaviors
with lack of guilt, remorse, and empathy [35].
In fact, the prevalence of ASPD can be up to five times higher (4.1%) [36] and appears
to be more frequently identified in BD I than BD II [37]. ASPD and BD are both character-
ized by impulsive behaviors [38,39] and substance use disorder [40–42] that frequently
lead to trouble with the law [43,44] and suicidal behavior [45,46]. Studies suggested that
impulsivity and the frequent abuse of drugs, especially alcohol, cannabis and ampheta-
mines, is associated with sensation seeking and a lack of premeditation in ASPD and that
when ASPD is co-morbid with BD it is associated with significant deficits in the ability to
delay reward [47–49] and greater gray matter volume in the mesolimbic reward system
[50]. These characteristics appear more severe when they are combined [50–52] and a more
in depth characterization of ASPD comorbidity in patients with BD may help clinicians to
distinguish both disorders and tailor the treatment. Thus, in an attempt to detect the fre-
quency of ASPD in bipolar patients with greater accuracy and to better clarify the rela-
tionship between ASPD and BD, we conducted a systematic review of the existing litera-
ture on the frequency of ASPD in BD I, BD II and cyclothymia, according to DSM or ICD
diagnostic criteria, evaluating the impact on clinical characteristics and outcomes.
2. Materials and Methods
2.1. Search Strategy
We searched PubMed, Embase, MEDLINE, and the Cochrane Library for articles
evaluating the comorbidity between BDs and ASPD published up to 1 December 2020. No
language or time restriction were applied. We used the following keywords: “bipolar dis-
order OR affective disorder OR mood disorder OR bipolar disorders OR affective disorders OR
mood disorders OR BD OR cyclothymia AND antisocial personality disorder OR ASPD OR
AABS OR adult antisocial behavior syndrome OR antisocial behavioral syndrome” sorted by best
match. Two researchers independently reviewed all the selected studies. Titles and ab-
stracts of the identified papers were reviewed, and full texts considered relevant were
recovered and revised. The reference lists of eligible studies were also hand-screened to
search additional and useful studies to be included in the review. To improve the clarity
of the review process, the PRISMA Statement criteria and recommendations were fol-
lowed [53]. Figure 1 shows the research strategy.
Medicina 2021, 57, 183 3 of 17
Figure 1. The PRISMA flow chart.
2.2. Assessment of Study Quality
Quality assessment was conducted using the Mixed Methods Appraisal Tool
(MMAT) developed by Pluye et al. [54]. Piloting suggested that the MMAT was a reliable
and efficient scoring system for appraising the quality of quantitative, qualitative, and
mixed-method studies. It provides a comprehensive manual with detailed instructions.
The methodology was evaluated using five criteria: qualitative, randomized controlled,
non-randomized, observational descriptive, mixed methods [55]. For each study, a score
of 20% was assigned if a criterion was met and 100% if all criteria were met, therefore the
total score could range between 20 and 100%. Studies were assigned quality scores by two
reviewers (E.A.C. and R.d.F.); scores ranged from 80% to 100%. The quality assessment
was finally reviewed and agreed upon the whole review team.
2.3. Selection Criteria
Original articles were reviewed and reported. Relevant publications were identified,
and the full texts of these articles were retrieved and reviewed. The reference lists of in-
cluded studies were also screened in order to search useful literature. Studies with pa-
tients diagnosed with BD I, BD II or cyclothymia and ASPD according to DSM or ICD
criteria, regardless of the phase of the disorder and/or pharmacological treatment, aged
18–65 (we excluded studies on adolescents because personality disorders are not diag-
nosed in childhood) were included in the review article. Studies with patients diagnosed
with BD I, BD II or cyclothymia and ASPD, younger than 18 and older than 65, with neu-
rological comorbidity, or traumatic brain injuries with loss of consciousness were ex-
cluded. We considered the studies concerning the lifetime prevalence of ASPD in BD.
2.4. Data Collection and Extraction
Two blind researchers (E.A.C. and R.d.F.) independently screened the titles and ab-
stracts of the identified articles and performed data extraction. Articles that met the eligi-
bility criteria were read in the full texts, and in cases of disagreement, such as selection
discrepancies, a third researcher (M.C.) made the final decision. Article data included first
Medicina 2021, 57, 183 4 of 17
author name, year of publication, sample size, diagnoses assessed in the study, scales of
measurement and statistical data.
3. Results
Initially, 3203 items were identified. After deletion of duplicates (226) by two review-
ers (E.A.C., R.d.F.), 2977 papers remained. Exclusion of papers by title and abstract was
made by two reviewers (E.A.C., R.d.F.) based on assessment of the inclusion and exclusion
criteria. This process ended in the exclusion of 2751 papers. The title and abstracts screen-
ing was performed for the remaining 226 articles. In all, we excluded 201 articles because
they were reviews, meta-analyses, letters to editors, editorials, guidelines, and case re-
ports. Some of them had only a bipolar subgroup or other personality disorder as a comor-
bidity, or the diagnosis was not clear. Then, 8 manuscripts out of 25 papers were deleted
because they did not fulfill the inclusion criteria: 5 papers included patients aged <18 or
>65, and 3 papers had unclear diagnosis focusing on personality disorders and not speci-
fying the diagnosis. The remaining 17 papers were deemed eligible and included in the
present review (Table 1). A great heterogeneity was reported among studies included and
wide variability in the sample number (from N = 21 to N = 43,093) [49,56]. ASPD preva-
lence in BD ranged between 4.8% and 63% [47,57] and was higher in BD I [37] than II
[17,49,58] and, in particular, in BD patients with substance use disorder (SUD) comorbid
[47–49] with combined cocaine and alcohol abuse was most frequent [48,49,59]. Patients
with BD and ASPD in comorbidity showed early onset [58], a higher number of depressive
and manic episodes [47], higher scores of depression [59] and psychosis [47], more aggres-
sive [60], and impulsive [47,61] traits and more suicide attempts [47]. The psychometric
tools used to assess the psychopathology were the Alcohol Use Disorder and Associated
Disabilities Interview Schedule (AUDADIS) [49,57], the 12-Item Short Form Survey (SF-
12) [49,57], the Barratt Impulsiveness Scale (BIS-11) [47,58], the Temperament Evaluation
of Memphis, Pisa, Paris and San Diego-auto-questionnaire version (TEMPS-A) [62], Ham-
ilton Depression Rating Scale (HDRS) [60,63], Young mania rating scale (YMRS) [60,63],
Brown–Goodwin Aggression Scale (BGA) [60], and the Schedule for Affective Disorders
and Schizophrenia (SADS-C) [47,63].
Medicina 2021, 57, 183 5 of 17
Table 1. The main characteristics of the included studies.
Authors, Years Sample Measurements Results Comments MMAT
Goldstein et al., 2017 [57] N = 36,309 AUDADIS-5; SF-12
Lifetime prevalence:
ASPD+BD1: 11.8%
AABS+BD1: 4.8%
OR (C.I.) lifetime of BD 1
comorbidity: ASPD 2.9
(1.93–4.28) AABS 1.9
(1.43–2.50)
Comorbidity is higher in
the ASPD than in the
AABS. Patients with ASPD
has a 3 times fold risk of
BD, while it is 2 times
greater if it has AABS
*****
Lev-Ran et al., 2013 [49] N = 43,093 AUDADIS-IV; SF-
12
12-month prevalence: BD
+ CUD + ASPD: 49.9%
BD + No CUD + ASPD:
18.2%
OR (C.I.):
2.75 (1.63–4.64)
The bipolar patient with
CUD is almost 3 times
more likely to have ASPD
than the bipolar patient
without CUD
*****
Swann et al., 2013 [58]
N = 55
4 BD II
51 BD I
14 = no Axis II dis-
order (8 men and 6
women)
35 ASPD (20
men and 15
women)
23 Borderline 8
men and 15
women
17 (7 men and
10 women) both
disorders
Diagnosis was
made by Structured
Clinical Interview
for DSM-IV
SCID-II
Schedule for Affec-
tive Disorders and
Schizophrenia
(SADS-C)
Barratt Impulsive-
ness Scale (BIS-11)
Prevalence:
35 ASPD of 55 BD:63%
17 ASPD + Borderline of
55: 30.9%.
Number of episodes:
ASPD symptoms pre-
dicted a history of many
depressive and manic ep-
isodes (but not either
type alone) and a early
onset.
BIS-11 score:
Total, motor, and atten-
tional BIS-11 scores were
predicted significantly by
borderline symptom
scores with no significant
contribution from ASPD
scores. Suicide attempts:
Impulsivity in ASPD +
ASPD symptoms were
more strongly related to
course of illness (i.e., early
age at onset, frequency of
affective episodes, suicide
attempts and substance-re-
lated disorders) but not to
impulsivity.
****
Medicina 2021, 57, 183 6 of 17
BD did not contribute
significantly to history of
suicide attempt
SUD Comorbidity:
ASPD symptoms pre-
dicted history of alcohol,
other substance-abuse
disorder, and smoking.
Mueser et al., 2012 [59] N = 103
SCID-II; Time-line
Follow-back Calen-
dar; AUS; DUS;
SATS; BPRS; GAS;
Knowledge Test;
SPSI; FAS; SF-12;
FEIS
Prevalence:
21 ASPD of which 11 BD:
52%
Over half of the antisocial
patients are also bipolar *****
Perugi et al., 2012 [62] N = 106 CGI-BP; TEMPS-A;
SAS; IPSM; SIMD-R
Prevalence:
BD I + ASPD: 8.49%
The authors evaluated the
impact of the affective
phase of BD1 on axis II di-
agnosis, concluding that
ASPD is more represented
among hyperthymic than
cyclothymic, depressive or
euthymic patients and af-
fective temperaments may
influence both clinical fea-
tures and axis I and II
comorbidities.
****
Swann et al., 2011 [61]
N = 133
46 HC
21 BD without per-
sonality disorders
50ASPD without
BD
16BD + ASPD
Immediate Memory
Task (IMT)
Two Choice Impul-
sivity Paradigm
(TCIP)
Prevalence:
16 ASPD of 37 BD:
43.24%
Impulsivity:
Impulsivity was in-
creased in the combined
disorders compared to
both disorders alone.
The combination of ASPD
and BD was associated
with more impulsive TCIP
performance compared to
HC. Compensatory mech-
anisms for impulsivity in
uncomplicated ASPD or
****
Medicina 2021, 57, 183 7 of 17
Outcome:
In combined ASPD and
BD increased reaction
speed, impulsive re-
sponse bias, and reward-
delay impulsivity oc-
curred. It was independ-
ent of substance-use dis-
order history.
BD appear to be compro-
mised or lost when the
disorders are in comorbid-
ity.
Goldstein et al., 2010 [17] N = 2442 AUDADIS-IV
Prevalence:
BD1 + ASPD: 45.1% (p <
0.0001) BD2 + ASPD:
8.2% (p < 0.0122)
BD1 + AABS: 32.4%
BD2 + AABS: 5.8%
In subjects with PTSD and
ASPD, comorbidity with
DB 1 is the strongest evi-
dence, that with DB 2, alt-
hough lower, however, is
statistically significant.
*****
Swann et al., 2010 [47]
N = 197
78 HC
34 ASPD
61 BD
24 BD + ASPD
SCID-II; SADS-C;
BIS-11
Prevalence:
12.4% of total sample
SADS-C score:
Higher scores of depres-
sion and psychosis
BIS-11 score:
higher subscale and total
score
Suicide attempts:
BD + ASPD: 65.4%
BD: 34.9%
SUD Comorbidity:
BD + ASPD: 91.3%
BD: 66.7%
Number of episodes:
Higher number of manic
and depressive episodes
Comorbidity is associated
with a greater tendency to
depression and psychosis,
an increased number of
depressive and manic epi-
sodes, greater impulsivity,
greater risk of SUD and
suicide.
****
Garno et al., 2008 [60]
N = 100
73 BD1
27 BD2
SCID-I; SCID-II;
HDRS; YMRS;
CTQ; BGA
Prevalence DB + ASPD:
6.25%
Comorbidity and BGA:
Bipolar patients with
ASPD have more aggres-
sive traits
****
Medicina 2021, 57, 183 8 of 17
Higher BGA total score
(p 0.008)
Mitchell et al., 2007 [48] N = 166 MINI
Prevalence
ASPD in BD + SUD%; OR
(C.I.):
BD + COCA: 52.8%; 1.86
(0.81–4.26)
BD + COCA +
ALCOL:60%; 2.50 (1.23–
5.08)
ASPD is more associated
with the bipolar group
with cocaine dependence
(almost twice the risk) or
cocaine plus alcohol (twice
and a half risk)
****
Maina et al., 2007 [19]
N = 204 BD = 21
BD I = 4; BD II = 17
BD + ASPD = 6
Yale-Brown Obses-
sive-Compulsive
Scale (Y-BOCS);
SCID-I; SCID-II;
Prevalence DB + ASPD:
6%
SUD Comorbidity:
SUD + BD: 28.6%.
Comorbidity: prevalence
of antisocial personality
disorders + BD: 28.6%
Clinically relevant effects
of comorbid BD on the
personality features of
OCD patients. A higher
rate of narcissistic and
ASPD in BD/OCD pa-
tients.
****
Mueser et al., 2006 [64] N = 178
SCID-I; SCID- II;
BPRS; GAS; TLFB;
ASI; AUS; DUS;
SATS
Prevalence BD + AABS:
21.2%
Prevalence BD + ASPD:
21.1%
The prevalence of AABS
and ASPD in the DB is su-
perimposable
****
Garno et al., 2005 [63]
N = 100
73 BD1
27 BD2
SCID-I; SCID-II;
CTQ; YMRS; HAM-
D; SADS-C
Prevalence BD + ASPD:
6%
There is no statistically
significant correlation be-
tween YMRS and HAM-D
scores with ASPD.
****
Mueser et al., 1999 [65]
No ASPD/CD = 293
CD Only = 293
Adult ASPD Only
= 293
Full ASPD = 293
Schizophrenia
(28%),
schizoaffective dis-
order (24%), bipo-
lar disorder (22%),
major depression.
SCID; MMS; CRS;
MAST; DAST;
CAGE; TACE;
TWEAK; ACI; AU-
DIT.
Prevalence
BD + Adult ASPD Only:
24%
Prevalence BD + Full
ASPD: 22%
SUD Comorbidity:
Full ASPD group had the
highest rate of substance
use disorder, followed by
either the CD Only or
Adult ASPD Only
Childhood CD and adult
ASPD represent inde-
pendently significant risk
factors for substance use
disorders in patients with
schizophrenia- spectrum
and major affective disor-
ders.
****
Medicina 2021, 57, 183 9 of 17
(19%) and other
(7%)
groups, with the No
ASPD/CD group lowest
Jackson & Pica, 1993 [66]
112 psychiatric in-
patients
11 antisocial per-
sonality disorder,
65 had other forms
of personality dis-
orders, 36 no per-
sonality disorder.
35 recent-onset
schizophrenic pa-
tients (27 men, 6
women), 26 recent-
onset bipolar disor-
der patients (14
men, 12 women),
30 unipolar affec-
tive disorder pa-
tients (14 men, 16
women), and 21
(11 men, 10
women) with
mixed disorders
(e.g., anorexia ner-
vosa, substance
abuse, somatoform
disorders)
SCID, Royal Park
Multidiagnostic In-
strument for Psy-
choses, SAPS,
SANS, BDI BRMS
Prevalence:
4 patients of 11 antisocial
are affected by BD.
Patients with ASPD were
younger, with lower level
of education and higher
levels of many dysfunc-
tional behaviors, as delin-
quency, sexual inter-
course, drink/drugs abuse,
thefts, vandalism, incon-
sistent work, irritabil-
ity/aggressive, impul-
sivity, recklessness, contin-
ual antisocial behavior
than patients with other or
none PDs.
****
Turley et al., 1992 [56]
21 recent onset BD
(12 man and 9
women)
MCMI-II); SIDP;
BDI; SAPS; BRMS;
SCID-P
The overall ratio of per-
sonality disorders identi-
fied was virtually equiva-
lent for the MCMI- I1 and
the SIDP. However, the
MCMI-I1 was far more
likely to make multiple
diagnoses than the SIDP.
Narcissistic and Antisocial
personality disorders were
the most prevalent disor-
ders in this sample of Bi-
polar disordered patients,
followed by Histrionic and
Passive-Aggressive disor-
ders
****
Medicina 2021, 57, 183 10 of 17
The MCMI-I1 identified a
total of 52 personality
disorders compared with
30 for the SIDP.
Pica et al., 1990 [67]
N = 26
16 BD
10 Schizoaffective
Disorder
SIDP; SCID-P;
RPMIP; BDI; BRMS;
SAPS; SANS
Prevalence
BD + ASPD: 15.39%
Patients with BD showed a
high frequency of PDs. ****
MMAT scores: ***** 100%; **** 80%; *** 60%; ** 40%; * 20%. AABS: Adult Antisocial behavioral syndrome; ACI: Alcohol Clinical Index; ASI: Addiction Severity Index; ASPD: Antisocial
personality disorder; AUDADIS: Alcohol Use Disorder and Associated Disabilities Interview Schedule; AUDIT: Alcohol Use Disorder Identification Test- Clinical Procedure; AUS: Alcol
Use Scale; BD: Bipolar Disorder; BDI: Beck Depression Inventory; BGAS: Brown-Goodwin Aggression Scale; BIS-11: Barratt Impulsivity Scale; BPRS: Brief Psychiatric Rating Scale;
BRMS: Bech-Rafaelsen Mania Scale; CAGE: Cut Down on Drinking, Annoyed, Guilt and Eye-opener Test; CGI-BP: Clinical Global Impression-BP; CTQ: Childhood Trauma Question-
naire; C.I.: Confidence Interval; CRS: Clinician Rating Scales; CUD: Cannabis Use Disorder; DAST: Drug Abuse Screening Test; DUS: Drugs Use Scale; FAS: Family Attitude Scale; FEIS:
Family Experiences Interview Schedule; GAS: Global Assessment Scale; HC: Healthy Control; HDRS: Hamilton. Depression Rating Scale; IMT: Immediate Memory Task; IPSM: Inter-
personal Sensitivity Measure; MAST: Michigan Alcohol Screening Test; MCMI-II: Millon Clinical Multiaxial Inventory; MINI: Mini International Neuropsychiatric Interview; MMAT:
mixed-method appraisal tool; MMS: Mini- Mental State; OCD: obsessive-compulsive disorder; OR: Odd Ratio; OR: adjusted Odd Ratio; PTSD: Post-Traumatic Stress Disorder; RPMIP:
Royal Park Multi- Diagnostic Instrument for Psychosis; SADS: Schedule for Affective Disorders and Schizophrenia; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale
for the Assessment of Positive Symptoms; SASI: Separation Anxiety Symptom Inventory; SATS: Substance Abuse Treatment Scale; SCID- I:Structured Clinical Interview for DSM-IV
Axis I Disorders; SCID-P: Structured Clinical Interview for Personality Disorders; SCID-II: Structured Clinical Interview for DSM-IV Axis II Disorders;SF-12: 12-Item Short Form Health
Survey; SIDP: Structured Interview for DSM-III personality; SIMD-R: Semi-structured interview for Mood Disorder; SPSI: Social Problem Solving Inventory; SUD: Substances Use
Disorder; TACE: Tolerance, Annoyed, Cut Down, and Eye- opener Test; TCIP: Two Choice Impulsivity Paradigm; TEMPS-A: Temperament Evaluation of Memphis, Pisa, Paris and San
Diego scale; TLFB: Time-line Follow-back; TWEAK: Tolerance, Worry, Eye-opener, Amnesia and Cut Down on drinking Test; YMRS: Young Mania Rating Scale.
Medicina 2021, 57, 183 11 of 17
4. Discussion
To the authors’ knowledge, this is the first systematic review that assessed the asso-
ciation and the impact of ASPD and BD. It is worth mentioning how scarce the studies are
that evaluate this association despite the high clinical relevance. The literature demon-
strated a high incidence of Axis II personality disorders in patients with DB [24,68] and
the more frequent were Cluster B personality disorders [19,25–27,69] followed by C and
A [17,47,58,67]. Antisocial personality disorders [59] together with narcissistic [19,70] and
histrionic personality disorder were diagnosed most frequently in BD patients, even in
recent-onset BD patients [56]. Pica et al., found that 62% of BD patients had PDs and ASPD
was present in 15–39% [67]. Moreover, as can be seen from the studies, a prevalence of
30% ASPD in BD was reported, with a superior incidence in BD I than in BD II. A greater
occurrence of antisocial behavior [29] and greater impulsivity during episodes, especially
during mania has been demonstrated [52]. The clinical severity due to the co-occurrence
of the two disorders and therefore the greater demand for access to clinical services could
explain this higher prevalence. This great variability found in this review (4.8% to 63%
[47,57]) may be due to the variable sample size and population selected of included stud-
ies (from N = 21 to N = 43,093) [49,56], the retrospective nature of the included studies, the
methodological differences (e.g., instruments used, phase of the disorder at the time col-
lection) that may negatively affect the ability to discriminate between ASPD and BD diag-
noses due to the high prevalence of BD in the general population and the lack of a precise
tool for ASPD diagnostic assessment.
As expected, ASPD in comorbidity with BD is associated with a more severe course
of illness and poor responsiveness and adherence to treatment [71,72]. ASPD in BD pa-
tients was associated with a poor outcome after a manic episode [73], a higher rate of
suicide attempts [63,74], and a worse course of illness [75], with greater service admission
[76]. Moreover, the greatest number of depressive events associated with the comorbidity
with PDs results in a reduction in the quality of life, and since this is the most frequent
suicide attempt during depressive phases, this may explain why patients with comorbid-
ity also have a greater tendency to attempt suicide [77]. Patients with BD and ASPD
showed an earlier onset of affective symptomatology [58], higher psychopathological bur-
den [58,63], and a higher number of affective episodes [47]. An earlier age at onset of the
antisocial behavior has been also described [32] that often persists in adulthood [78]. No-
tably, earlier onset is associated with a poorer prognosis in both disorders [79,80], proba-
bly due not only to the genetic contribution [81,82] but also to the environmental influ-
ences (e.g., child maltreatment, abuse, violence, harsh and inconsistent parental discipline,
and lower quality caregiving) [83,84]. These patients have been also found to have a
higher score of aggressivity measured with the BGA [60], higher impulsivity measured by
the BIS-11 [47,58,61], and more suicide attempts [47]. Manic episodes can more easily lead
to criminal penalties, illegal conduct therefore indirectly impacts treatment adherence
[85]. Low treatment rates were found in patients with ASPD [57] and reflect affected indi-
viduals’ lack of insight into the seriousness of their problem and consequently lack of ef-
fective interventions. Even if BD demonstrated a higher rate of treatment compared to
patients affected by ASPD, the co-occurrence of two disorders, often in younger patients,
may interfere with treatment, as well as the ability to adhere to the treatment, with conse-
quent poor outcome [59].
ASPD symptoms were associated with a history of alcohol or other SUDs as well as
smoking. Substance abuse before 15 years is strongly related to ASPD [64,86] and ASPD
symptoms were related to age at BD onset independently of gender [58]. Lev-Ran and
colleagues estimated the 12-month prevalence of BD, SUD (cannabis), and ASPD as 49.9%,
compared to 18.2% of patients with BD and without SUD [49]. Studies described cocaine
and alcohol combined abuse as most frequent in BD and ASPD [48,49]. A more severe
course of illness was found in comorbid SUD in bipolar patients, including an earlier on-
set, more rapid progression to dependence, and greater social, legal, and physical use con-
Medicina 2021, 57, 183 12 of 17
sequences [64]. The frequent comorbidity with addictive disorders, suicidality, and crim-
inal behaviors described, could be probably due to a shared impulsivity core feature [52].
A high level of impulsivity has been shown in patients affected by BD in comorbidity with
ASPD measured by the Immediate Memory Task (IMT) and Two Choice Impulsivity Par-
adigm (TCIP). Moreover, faster Immediate Memory Task (IMT) reaction times in BD com-
bined with SUD compared to BD alone have been reported [52]. The results suggest that
loss of compensatory mechanisms may lead to more severe impulsivity in the combined
disorders [52]. Another important aspect is the influence of temperament, which, in BD
patients, can give rise to the predisposition to develop ASPD. Perugi et al. evaluated the
influence of the affective temperament and psychopathological traits in a sample of pa-
tients with BD I and ASPD and found a higher incidence of hyperthymic temperaments
in this population (8.49%) [62], suggesting that affective temperament influences clinical
features of BD when in comorbidity with Axis II disorders [62].
Thus, comorbidity with ASPD seems to impact not only the onset but also the cyclical
nature of BD, increasing the number of episodes, psychopathological scores, suicide at-
tempts, and poor adherence to treatment (Figures 2 and 3). Considering the shared symp-
toms such as impulsive and dangerous behaviors (i.e., substance abuse, driving recklessly,
inappropriate sexual behavior), in patients with only one disease, misdiagnosis is a com-
mon phenomenon due to the overlapping symptoms of ASPD and BD. It may be useful
to recognize the co-occurrence of the disorders and disentangle whether the two disorders
are independent or interdependent conditions.
Figure 2. Main results.
Medicina 2021, 57, 183 13 of 17
Figure 3. Overlapping symptoms between ASPD and BD.
Limits and Future Directions
This review presents gray areas that deserve to be further explored. Potential limita-
tions to consider include: (1) studies selected often determine the course of illness retro-
spectively. Moreover, many studies enrolled patients regardless of the phase of the illness.
The results of the diagnostic assessments may be affected by the state of illness, thus re-
ducing the quality of the included studies; (2) great heterogeneity and wide variability in
the sample number and population selected was reported among studies making it diffi-
cult to correctly define the prevalence; (3) mechanisms underlying ASPD or AABS char-
acteristics may be different in individuals with BD compared to those without BD; 4) ad-
ditional comorbidities with further personality disorders were not systematically evalu-
ated by the included studies. Although this does not affect the epidemiological results, it
could limit their psychopathological interpretation. It should be necessary to better char-
acterize comorbidity, evaluating all dysfunctional aspects of diseases and how they could
influence core symptoms and comorbidity. It may be necessary to evaluate psychopathy
within BD, as it is plausible that comorbid antisocial traits are different from the psycho-
antisocial traits. It should also be necessary to evaluate whether patient profiles with
comorbidity could benefit from different treatments. Psychopathy has not been investi-
gated because of the difficulty of its classification according to DSM in relation to ASPD.
5. Conclusions
ASPD was estimated as more frequent among BD patients, especially in BD type I.
BD patients with ASPD as a comorbidity seemed to have early onset, a higher number of
manic and depressive episodes, more severe affective episodes, higher levels of aggressive
and impulsive behaviors. Comorbidity is associated with a worse prognosis, increased
frequency of relapse, poor clinical outcome, higher frequency of dangerous behaviors, a
higher rate of suicide attempts and poorer treatment adherence. Furthermore, ASPD
symptoms in BD patients seem to be also associated with frequent comorbidity with ad-
dictive disorders (alcohol or cocaine abuse disorder), suicidality, and criminal behaviors,
probably due to a shared impulsivity core feature. Therefore, we suggest better character-
ization of the patient with BD and ASPD. Based on the literature data, considering the
comorbidity between BD and ASPD and common elements between ASPD and psychop-
athy, it would be desirable to carry out clinical trials that also investigate in-depth the
comorbidity among the three conditions together. Indeed, the presence of psychopathy in
patients with BD and ASPD may have important consequences in clinical, prognostic, and
therapeutic terms.
Medicina 2021, 57, 183 14 of 17
Author Contributions: Ideation, P.D.F.; literature search and data analysis, E.A.C., R.d.F. and M.C.;
writing—original draft preparation, E.A.C., R.d.F., M.C. and L.S.Jr.; writing—review and editing,
E.A.C., R.d.F., L.D., L.S.J. and P.D.F. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data available on request.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Grande, I.; Berk, M.; Birmaher, B.; Vieta, E. Bipolar disorder. Lancet 2016, 387, 1561–1572.
2. Jann, M.W. Diagnosis and treatment of bipolar disorders in adults: A review of the evidence on pharmacologic treatments. Am.
Health Drug Benefits 2014, 7, 489–99.
3. Merikangas, K.R.; Jin, R.; He, J.-P.; Kessler, R.C.; Lee, S.; Sampson, N.A.; Viana, M.C.; Andrade, L.H.; Hu, C.; Karam, E.G.; et al.
Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative. Arch. Gen. Psychiatry
2011, 68, 241.
4. Koirala, P.; Hu, B.; Altinay, M.; Li, M.; DiVita, A.L.; Bryant, K.A.; Karne, H.S.; Fiedorowicz, J.G.; Anand, A. Sub-threshold bipolar
disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment
response. J. Psychiatr. Res. 2019, 110, 1–8.
5. Sinha, A.; Shariq, A.; Said, K.; Sharma, A.; Jeffrey Newport, D.; Salloum, I.M. Medical Comorbidities in Bipolar Disorder. Curr.
Psychiatry Rep. 2018, 20, 36.
6. Judd, L.L.; Akiskal, H.S.; Schettler, P.J.; Endicott, J.; Maser, J.; Solomon, D.A.; Leon, A.C.; Rice, J.A.; Keller, M.B. The long-term
natural history of the weekly symptomatic status of bipolar I disorder. Arch. Gen. Psychiatry 2002, 59, 530–537.
7. Chen, M.; Fitzgerald, H.M.; Madera, J.J.; Tohen, M. Functional outcome assessment in bipolar disorder: A systematic literature
review. Bipolar Disord. 2019, 21, 194–214.
8. Amerio, A.; Odone, A.; Tonna, M.; Stubbs, B.; Ghaemi, S.N. Bipolar disorder and its comorbidities between Feinstein and the
Diagnostic and Statistical Manual of Mental Disorders. Aust. N. Z. J. Psychiatry 2015, 49, 1073.
9. Di Florio, A.; Craddock, N.; van den Bree, M. Alcohol misuse in bipolar disorder. A systematic review and meta-analysis of
comorbidity rates. Eur. Psychiatry 2014, 29, 117–24.
10. Hunt, G.E.; Malhi, G.S.; Cleary, M.; Lai, H.M.X.; Sitharthan, T. Prevalence of comorbid bipolar and substance use disorders in
clinical settings, 1990-2015: Systematic review and meta-analysis. J. Affect. Disord. 2016, 206, 331–349.
11. Hunt, G.E.; Malhi, G.S.; Cleary, M.; Lai, H.M.X.; Sitharthan, T. Comorbidity of bipolar and substance use disorders in national
surveys of general populations, 1990–2015: Systematic review and meta-analysis. J. Affect. Disord. 2016, 206, 321–330.
12. Nabavi, B.; Mitchell, A.J.; Nutt, D. A Lifetime Prevalence of Comorbidity Between Bipolar Affective Disorder and Anxiety
Disorders: A Meta-analysis of 52 Interview-based Studies of Psychiatric Population. EBioMedicine 2015, 2, 1405–1419.
13. Pavlova, B.; Perlis, R.H.; Mantere, O.; Sellgren, C.M.; Isometsä, E.; Mitchell, P.B.; Alda, M.; Uher, R. Prevalence of current anxiety
disorders in people with bipolar disorder during euthymia: A meta-analysis. Psychol. Med. 2017, 47, 1107–1115.
14. Forty, L.; Ulanova, A.; Jones, L.; Jones, I.; Gordon-Smith, K.; Fraser, C.; Farmer, A.; McGuffin, P.; Lewis, C.M.; Hosang, G.M.; et
al. Comorbid medical illness in bipolar disorder. Br. J. Psychiatry 2014, 205, 465–472.
15. McElroy, S.L.; Altshuler, L.L.; Suppes, T.; Keck, P.E.; Frye, M.A.; Denicoff, K.D.; Nolen, W.A.; Kupka, R.W.; Leverich, G.S.;
Rochussen, J.R.; et al. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar
disorder. Am. J. Psychiatry 2001, 158, 420–426.
16. Preti, A.; Vrublevska, J.; Veroniki, A.A.; Huedo-Medina, T.B.; Kyriazis, O.; Fountoulakis, K.N. Prevalence and treatment of panic
disorder in bipolar disorder: Systematic review and meta-analysis. Evid. Based. Ment. Health 2018, 21, 53–60.
17. Goldstein, R.B.; Compton, W.M.; Grant, B.F. Antisocial Behavioral Syndromes and Additional Psychiatric Comorbidity in
Posttraumatic Stress Disorder Among U.S. Adults: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and
Related Conditions. J. Am. Psychiatr. Nurses Assoc. 2010, 16, 145–165.
18. Hossain, S.; Mainali, P.; Bhimanadham, N.N.; Imran, S.; Ahmad, N.; Patel, R.S. Medical and Psychiatric Comorbidities in Bipolar
Disorder: Insights from National Inpatient Population-based Study. Cureus 2019, 11, e5636.
19. Maina, G.; Albert, U.; Pessina, E.; Bogetto, F. Bipolar obsessive-compulsive disorder and personality disorders. Bipolar Disord.
2007, 9, 722–729.
20. Simon, N.M.; Otto, M.W.; Wisniewski, S.R.; Fossey, M.; Sagduyu, K.; Frank, E.; Sachs, G.S.; Nierenberg, A.A.; Thase, M.E.;
Pollack, M.H. Anxiety disorder comorbidity in bipolar disorder patients: Data from the first 500 participants in the Systematic
Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am. J. Psychiatry 2004, 161, 2222–2229.
Medicina 2021, 57, 183 15 of 17
21. Thiebaut, S.; Godart, N.; Radon, L.; Courtet, P.; Guillaume, S. Crossed prevalence results between subtypes of eating disorder
and bipolar disorder: A systematic review of the literature. Encephale 2019, 45, 60–73.
22. Pinna, M.; Visioli, C.; Rago, C.M.; Manchia, M.; Tondo, L.; Baldessarini, R.J. Attention deficit-hyperactivity disorder in adult
bipolar disorder patients. J. Affect. Disord. 2019, 243, 391–396.
23. Cerimele, J.M.; Bauer, A.M.; Fortney, J.C.; Bauer, M.S. Patients with co-occurring bipolar disorder and posttraumatic stress
disorder: A rapid review of the literature. J. Clin. Psychiatry 2017, 78, e506–e514.
24. Bezerra-Filho, S.; Almeida, A.G.; Studart, P.; Rocha, M.V.; Lopes, F.L.; Miranda-Scippa, Â. Personality disorders in euthymic
bipolar patients: A systematic review. Rev. Bras. Psiquiatr. 2015, 37, 162–167.
25. Fan, A.H.; Hassell, J. Bipolar disorder and comorbid personality psychopathology: A review of the literature. J. Clin. Psychiatry
2008, 69, 1794–1803.
26. Harnic, D.; Catalano, V.; Mazza, M.; Janiri, L.; Bria, P. An observational study evaluating comorbidity between bipolar disorder
and personality disorders. Clin. Ter. 2010, 161, 51–54.
27. Friborg, O.; Martinsen, E.W.; Martinussen, M.; Kaiser, S.; Øvergård, K.T.; Rosenvinge, J.H. Comorbidity of personality disorders
in mood disorders: A meta-analytic review of 122 studies from 1988 to 2010. J. Affect. Disord. 2014, 152–154, 1–11.
28. Fowler, J.C.; Madan, A.; Allen, J.G.; Oldham, J.M.; Frueh, B.C. Differentiating bipolar disorder from borderline personality
disorder: Diagnostic accuracy of the difficulty in emotion regulation scale and personality inventory for DSM-5. J. Affect. Disord.
2019, 245, 856–860.
29. Quanbeck, C.D.; Stone, D.C.; Scott, C.L.; McDermott, B.E.; Altshuler, L.L.; Frye, M.A. Clinical and legal correlates of inmates
with bipolar disorder at time of criminal arrest. J. Clin. Psychiatry 2004, 65, 198–203.
30. Yen, S.; Frazier, E.; Hower, H.; Weinstock, L.M.; Topor, D.R.; Hunt, J.; Goldstein, T.R.; Goldstein, B.I.; Gill, M.K.; Ryan, N.D.; et
al. Borderline personality disorder in transition age youth with bipolar disorder. Acta Psychiatr. Scand. 2015, 132, 270–280.
31. Post, R.M.; McElroy, S.; Kupka, R.; Suppes, T.; Hellemann, G.; Nolen, W.; Frye, M.; Keck, P.; Grunze, H.; Rowe, M. Axis II
personality disorders are linked to an adverse course of bipolar disorder. J. Nerv. Ment. Dis. 2018, 206, 469–472.
32. Latalova, K.; Prasko, J.; Kamaradova, D.; Sedlackova, J.; Ociskova, M. Comorbidity bipolar disorder and personality disorders.
Neuro Endocrinol. Lett. 2013, 34, 1–8.
33. Fazel, S.; Lichtenstein, P.; Grann, M.; Goodwin, G.M.; Långström, N. Bipolar disorder and violent crime: New evidence from
population-based longitudinal studies and systematic review. Arch. Gen. Psychiatry 2010, 67, 931–938.
34. Apfelbaum, S.; Regalado, P.; Herman, L.; Teitelbaum, J.; Gagliesi, P. Comorbidity between Bipolar Disorder and Cluster B
Personality Disorders as indicator of affective dysregulation and clinical severity. Actas Esp. Psiquiatr. 2013, 41, 269–278.
35. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. DSM-5; 5th ed.; Washington, DC, USA,
2013.
36. Samuels, J.; Eaton, W.W.; Bienvenu, O.J.; Brown, C.H.; Costa, P.T.; Nestadt, G. Prevalence and correlates of personality disorders
in a community sample. Br. J. Psychiatry 2002, 180, 536–542.
37. Lenzenweger, M.F. Current status of the scientific study of the personality disorders: An overview of epidemiological,
longitudinal, experimental psychopathology, and neurobehavioral perspectives. J. Am. Psychoanal. Assoc. 2010, 58, 741–778.
38. Etain, B.; Mathieu, F.; Liquet, S.; Raust, A.; Cochet, B.; Richard, J.R.; Gard, S.; Zanouy, L.; Kahn, J.P.; Cohen, R.F.; et al. Clinical
features associated with trait-impulsiveness in euthymic bipolar disorder patients. J. Affect. Disord. 2013, 144, 240–247.
39. Turner, D.; Sebastian, A.; Tüscher, O. Impulsivity and Cluster B Personality Disorders. Curr. Psychiatry Rep. 2017, 19, 15.
40. Helle, A.C.; Watts, A.L.; Trull, T.J.; Sher, K.J. Alcohol use disorder and antisocial and borderline personality disorders. Alcohol
Res. Curr. Rev. 2019, 40, e1–e16.
41. González, E.; Arias, F.; Szerman, N.; Vega, P.; Mesias, B.; Basurte, I. Coexistence between personality disorders and substance
use disorder. Madrid study about prevalence of dual pathology. Actas Esp. Psiquiatr. 2019, 47, 218–228.
42. Messer, T.; Lammers, G.; Müller-Siecheneder, F.; Schmidt, R.F.; Latifi, S. Substance abuse in patients with bipolar disorder: A
systematic review and meta-analysis. Psychiatry Res. 2017, 253, 338–350.
43. Fovet, T.; Geoffroy, P.A.; Vaiva, G.; Adins, C.; Thomas, P.; Amad, A. Individuals with bipolar disorder and their relationship
with the criminal justice system: A critical review. Psychiatr. Serv. 2015, 66, 348–353.
44. Spaans, M.; Barendregt, M.; Haan, B.; Nijman, H.; de Beurs, E. Diagnosis of antisocial personality disorder and criminal
responsibility. Int. J. Law Psychiatry 2011, 34, 374–378.
45. Icick, R.; Melle, I.; Etain, B.; Ringen, P.A.; Aminoff, S.R.; Leboyer, M.; Aas, M.; Henry, C.; Bjella, T.D.; Andreassen, O.A.; et al.
Tobacco smoking and other substance use disorders associated with recurrent suicide attempts in bipolar disorder. J. Affect.
Disord. 2019, 256, 348–357.
46. Links, P.S.; Gould, B.; Ratnayake, R. Assessing suicidal youth with antisocial, borderline, or narcissistic personality disorder.
Can. J. Psychiatry 2003, 48, 301–310.
47. Swann, A.C.; Lijffijt, M.; Lane, S.D.; Steinberg, J.L.; Moeller, F.G. Interactions between bipolar disorder and antisocial personality
disorder in trait impulsivity and severity of illness. Acta Psychiatr. Scand. 2010, 121, 453–461.
48. Mitchell, J.D.; Brown, E.S.; Rush, A.J. Comorbid disorders in patients with bipolar disorder and concomitant substance
dependence. J. Affect. Disord. 2007, 102, 281–287.
49. Lev-Ran, S.; Le Foll, B.; McKenzie, K.; George, T.P.; Rehm, J. Bipolar disorder and co-occurring cannabis use disorders:
Characteristics, co-morbidities and clinical correlates. Psychiatry Res. 2013, 209, 459–465.
50. Glenn, A.L.; Johnson, A.K.; Raine, A. Antisocial Personality Disorder: A Current Review. Curr. Psychiatry Rep. 2013, 15, 427.
Medicina 2021, 57, 183 16 of 17
51. Fridell, M.; Hesse, M.; Jæger, M.M.; Kühlhorn, E. Antisocial personality disorder as a predictor of criminal behaviour in a
longitudinal study of a cohort of abusers of several classes of drugs: Relation to type of substance and type of crime. Addict.
Behav. 2008, 33, 799–811.
52. Swann, A.C. Antisocial personality and bipolar disorder: Interactions in impulsivity and course of illness. Neuropsychiatry
(London). 2011, 1, 599–610.
53. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.A.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.;
Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare
interventions: Explanation and elaboration. Br. Med J. 2009, 339, b2700.
54. Pluye, P.; Gagnon, M.P.; Griffiths, F.; Johnson-Lafleur, J. A scoring system for appraising mixed methods research, and
concomitantly appraising qualitative, quantitative and mixed methods primary studies in Mixed Studies Reviews. Int. J. Nurs.
Stud. 2009, 46, 529–546.
55. Hong, Q.N.; Fàbregues, S.; Bartlett, G.; Boardman, F.; Cargo, M.; Dagenais, P.; Gagnon, M.P.; Griffiths, F.; Nicolau, B.; O’Cathain,
A.; et al. The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers. Educ. Inf.
2018, 34, 285–291.
56. Turley, B.; Bates, G.W.; Edwards, J.; Jackson, H.J. MCMI-II personality disorders in recent-onset bipolar disorders. J. Clin. Psychol.
1992, 48, 320–329.
57. Goldstein, R.B.; Chou, S.P.; Saha, T.D.; Smith, S.M.; Jung, J.; Zhang, H.; Pickering, R.P.; Ruan, W.J.; Huang, B.; Grant, B.F. The
Epidemiology of Antisocial Behavioral Syndromes in Adulthood. J. Clin. Psychiatry 2017, 78, 90–98.
58. Swann, A.C.; Lijffijt, M.; Lane, S.D.; Steinberg, J.L.; Moeller, F.G. Antisocial personality disorder and borderline symptoms are
differentially related to impulsivity and course of illness in bipolar disorder. J. Affect. Disord. 2013, 148, 384–390.
59. Mueser, K.T.; Gottlieb, J.D.; Cather, C.; Glynn, S.M.; Zarate, R.; Smith, M.F.; Clark, R.E.; Wolfe, R. Antisocial personality disorder
in people with co-occurring severe mental illness and substance use disorders: Clinical, functional, and family relationship
correlates. Psychosis 2012, 4, 52–62.
60. Garno, J.L.; Gunawardane, N.; Goldberg, J.F. Predictors of trait aggression in bipolar disorder. Bipolar Disord. 2008, 10, 285–92.
61. Swann, A.C.; Lijffijt, M.; Lane, S.D.; Steinberg, J.L.; Moeller, F.G. Interacting mechanisms of impulsivity in bipolar disorder and
antisocial personality disorder. J. Psychiatr. Res. 2011, 45, 1477–1482.
62. Perugi, G.; Toni, C.; Maremmani, I.; Tusini, G.; Ramacciotti, S.; Madia, A.; Fornaro, M.; Akiskal, H.S. The influence of affective
temperaments and psychopathological traits on the definition of bipolar disorder subtypes: A study on Bipolar I Italian National
sample. J. Affect. Disord. 2012, 136, e41–e49.
63. Garno, J.L.; Goldberg, J.F.; Ramirez, P.M.; Ritzler, B.A. Bipolar disorder with comorbid cluster B personality disorder features:
Impact on suicidality. J. Clin. Psychiatry 2005, 66, 339–345.
64. Mueser, K.T.; Crocker, A.G.; Frisman, L.B.; Drake, R.E.; Covell, N.H.; Essock, S.M. Conduct disorder and antisocial personality
disorder in persons with severe psychiatric and substance use disorders. Schizophr. Bull. 2006, 32, 626–636.
65. Mueser, K.T.; Rosenberg, S.D.; Drake, R.E.; Miles, K.M.; Wolford, G.; Vidaver, R.; Carrieri, K. Conduct disorder, antisocial
personality disorder and substance use disorders in schizophrenia and major affective disorders. J. Stud Alcohol. 1999, 60, 278–
284.
66. Jackson, H.J.; Pica, S. An investigation into the internal structure of DSM-III antisocial personality disorder. Psychol. Rep. 1993,
72, 355–367.
67. Pica, S.; Edwards, J.; Jackson, H.J.; Bell, R.C.; Bates, G.W.; Rudd, R.P. Personality disorders in recent-onset bipolar disorder.
Compr. Psychiatry 1990, 31, 499–510.
68. Mantere, O.; Melartin, T.K.; Suominen, K.; Rytsälä, H.J.; Valtonen, H.M.; Arvilommi, P.; Leppämäki, S.; Isometsä, E.T.
Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder. J. Clin. Psychiatry
2006, 67, 584–593.
69. Berk, M.; Dodd, S. Bipolar II disorder: A review. Bipolar Disord. 2005, 7, 11–21.
70. Ravizza, L.; Barzega, G.; Bellino, S.; Bogetto, F.; Maina, G. Predictors of drug treatment response in obsessive-compulsive
disorder. J. Clin. Psychiatry 1995, 56, 368–373.
71. Crawford, T.N.; Cohen, P.; First, M.B.; Skodol, A.E.; Johnson, J.G.; Kasen, S. Comorbid Axis I and Axis II disorders in early
adolescence: Outcomes 20 years later. Arch. Gen. Psychiatry 2008, 65, 641–648.
72. Post, R.M.; Leverich, G.S.; McElroy, S.; Kupka, R.; Suppes, T.; Altshuler, L.; Nolen, W.; Frye, M.; Keck, P.; Grunze, H.; et al.
Prevalence of axis II comorbidities in bipolar disorder: Relationship to mood state. Bipolar Disord. 2018, 20, 303–312.
73. Dunayevich, E.; Sax, K.W.; Keck, P.E.; McElroy, S.L.; Sorter, M.T.; McConville, B.J.; Strakowski, S.M. Twelve-month outcome in
bipolar patients with and without personality disorders. J. Clin. Psychiatry 2000, 61, 134–139.
74. Leverich, G.S.; Altshuler, L.L.; Frye, M.A.; Suppes, T.; Keck, P.E.; McElroy, S.L.; Denicoff, K.D.; Obrocea, G.; Nolen, W.A.; Kupka,
R.; et al. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar
Network. J. Clin. Psychiatry 2003, 64, 506–515.
75. Kay, J.H.; Altshuler, L.L.; Ventura, J.; Mintz, J. Impact of axis II comorbidity on the course of bipolar illness in men: A
retrospective chart review. Bipolar Disord. 2002, 4, 237–242.
76. Lembke, A.; Miklowitz, D.J.; Otto, M.W.; Zhang, H.; Wisniewski, S.R.; Sachs, G.S.; Thase, M.E.; Ketter, T.A.; STEP-BD
Investigators Psychosocial service utilization by patients with bipolar disorders: Data from the first 500 participants in the
Systematic Treatment Enhancement Program. J. Psychiatr. Pract. 2004, 10, 81–87.
Medicina 2021, 57, 183 17 of 17
77. Jylhä, P.; Rosenström, T.; Mantere, O.; Suominen, K.; Melartin, T.; Vuorilehto, M.; Holma, M.; Riihimäki, K.; Oquendo, M.A.;
Keltikangas-Järvinen, L.; et al. Personality disorders and suicide attempts in unipolar and bipolar mood disorders. J. Affect.
Disord. 2016, 190, 632–639.
78. Johansson, P.; Kerr, M.; Andershed, H. Linking adult psychopathy with childhood hyperactivity-impulsivity-attention
problems and conduct problems through retrospective self-reports. J. Pers. Disord. 2005, 19, 94–101.
79. Black, D.W. The natural history of antisocial personality disorder. Can. J. Psychiatry 2015, 60, 309–314.
80. Connor, D.F.; Ford, J.D.; Pearson, G.S.; Scranton, V.L.; Dusad, A. Early-Onset Bipolar Disorder: Characteristics and Outcomes
in the Clinic. J. Child Adolesc. Psychopharmacol. 2017, 27, 875–883.
81. Croarkin, P.E.; Luby, J.L.; Cercy, K.; Geske, J.R.; Veldic, M.; Simonson, M.; Joshi, P.T.; Wagner, K.D.; Walkup, J.T.; Nassan, M.M.;
et al. Genetic risk score analysis in early-onset bipolar disorder. J. Clin. Psychiatry 2017, 78, 1337–1343.
82. Ferguson, C.J. Genetic contributions to antisocial personality and behavior: A meta-analytic review from an evolutionary
perspective. J. Soc. Psychol. 2010, 150, 160–180.
83. Shi, Z.; Bureau, J.F.; Easterbrooks, M.A.; Zhao, X.; Lyons-Ruth, K. Childhood maltreatment and prospectively observed quality
of early care as predictors of antisocial personality disorder features. Infant Ment. Health J. 2012, 33, 55–69.
84. Agnew-Blais, J.; Danese, A. Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: A systematic
review and meta-analysis. Lancet Psychiatry 2016, 3, 342–349.
85. Sparding, T.; Pålsson, E.; Joas, E.; Hansen, S.; Landén, M. Personality traits in bipolar disorder and influence on outcome. BMC
Psychiatry 2017, 17, 159.
86. Fulwiler, C.; Grossman, H.; Forbes, C.; Ruthazer, R. Early-onset substance abuse and community violence by outpatients with
chronic mental illness. Psychiatr. Serv. 1997, 48, 1181–1185.
