Journal of Affective Disorders 217 (2017) 29–33

Contents lists available at ScienceDirect

Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research paper

Clinical correlates of acute bipolar depressive episode with psychosis MARK

a,b,⁎ b,c b b
Marco Antonio Caldieraro , Louisa G. Sylvia , Steven Dufour , Samantha Walsh ,
Jessica Janosb, Dustin J. Rabideaud, Masoud Kamalib,c, Melvin G. McInnise, William V. Bobof,
Edward S. Friedmang, Keming Gaoh, Mauricio Toheni, Noreen A. Reilly-Harringtonb,c, Terence
A. Ketterj, Joseph R. Calabreseh, Susan L. McElroyk,l, Michael E. Thasem, Richard C. Sheltong,
Charles L. Bowdenn, James H. Kocsiso, Thilo Deckersbachb,c, Andrew A. Nierenbergb,c
a
Serviço de Psiquiatria, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
b
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
c
Harvard Medical School, Boston, MA, USA
d
Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA
e
Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
f
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
g
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
h
Mood Disorders Program, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA
i
Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
j
Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA USA
k
Lindner Center of HOPE, Mason, OH, USA
l
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA
m
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
n
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA
o
Department of Psychiatry, Weill Cornell Medical College, Ithaca, NY, USA

A R T I C L E I N F O A BS T RAC T

Keywords: Background: Psychotic bipolar depressive episodes remain remarkably understudied despite being common
Bipolar disorder and having a significant impact on bipolar disorder. The aim of this study is to identify the characteristics of
Bipolar depression depressed bipolar patients with current psychosis compared to those without psychosis.
Psychosis Methods: We used baseline data of a comparative effectiveness study of lithium and quetiapine for bipolar
disorder (the Bipolar CHOICE study) to compare demographic, clinical, and functioning variables between
those with and without psychotic symptoms. Of the 482 participants, 303 (62.9%) were eligible for the present
study by meeting DSM-IV criteria for an acute bipolar depressive episode. Univariate analyses were conducted
first, and then included in a model controlling for symptom severity.
Results: The sample was composed mostly of women (60.7%) and the mean age was 39.5 ± 12.1 years.
Psychosis was present in 10.6% (n=32) of the depressed patients. Psychotic patients had less education, lower
income, and were more frequently single and unemployed. Psychosis was also associated with a more severe
depressive episode, higher suicidality, more comorbid conditions and worse functioning. Most group differences
disappeared when controlling for depression severity.
Limitations: Only outpatients were included and the presence of psychosis in previous episodes was not
assessed.
Conclusion: Psychosis during bipolar depressive episodes is present even in an outpatient sample. Psychotic,
depressed patients have worse illness outcomes, but future research is necessary to confirm if these outcomes
are only associated with the severity of the disorder or if some of them are independent of it.

1. Introduction and Harrow, 2016; Østergaard et al., 2013) and is associated with
worse prognosis, lower rates of recovery (Goghari and Harrow, 2016;
Psychosis is a frequent feature in bipolar disorder (BD) (Goghari Solomon et al., 2010) and shorter time to first recurrence (Pallaskorpi

⁎
Correspondence to: Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcellos, 2350. 4° andar. Serviço de Psiquiatria, Postal Code: 90035-003, Brazil.
E-mail address: mcaldieraro@hcpa.edu.br (M.A. Caldieraro).

http://dx.doi.org/10.1016/j.jad.2017.03.059
Received 21 November 2016; Received in revised form 24 January 2017; Accepted 5 March 2017
0165-0327/ © 2017 Elsevier B.V. All rights reserved.
M.A. Caldieraro et al.
et al., 2015) including first episode patients (Tohen et al., 2003). Most
studies of psychotic symptoms in BD focus on psychotic mania,
because psychotic symptoms are more common in manic episodes
(Altamura et al., 2015; Mantere et al., 2004). However, psychosis is
also frequent in bipolar depressive episodes. According to Fountoulakis
et al. (2016), the prevalence of psychosis in bipolar depression could be
as high as 66% in historical descriptions. More recent studies report
lower but still significant prevalence: 10.4% for a current episode
(Mantere et al., 2004) and 10–28% for lifetime bipolar depressive
episodes (Frankland et al., 2015; Goes et al., 2007; Rosenthal et al.,
1980). Moreover, major depressive episodes with psychosis are more
frequent (Frankland et al., 2015; Goes et al., 2007; Zaninotto et al.,
2015) and more recurrent (Mitchell et al., 2001) in BD than in unipolar
depression. First episodes of psychotic depression in 30% of cases are
likely to switch diagnosis to bipolar disorder (Tohen et al., 2012).
Psychotic depression is also associated with a more frequent history of
suicidality (when compared to psychotic manic or mixed episodes)
(Dell'Osso et al., 2000) and a reduction of gray matter volume in the
dorsolateral prefrontal cortex and in the insula (Radaelli et al., 2014)
further highlighting the potentially negative impact of psychosis during
bipolar depressive episodes.
Despite the prevalence and possible impact of psychosis in bipolar
depression, the differences between psychotic and nonpsychotic de-
pressive episodes are understudied. To date, only one study compared
psychotic (N=59) with nonpsychotic (N=176) outpatient bipolar de-
pression (Benazzi, 1999). This study enrolled highly selective patients,
or only those in an outpatient private practice of the author, and
assessed only a limited number of features. The aim of the current
study was to build upon Benazzi's data to compare acutely depressed
bipolar patients with and without current psychosis from the Bipolar
Clinical Health Outcomes Initiative in Comparative Effectiveness
(Bipolar CHOICE) study sample (Nierenberg et al., 2016) in terms of
demographic characteristics, clinical presentation and functioning.
2. Methods
The Bipolar CHOICE study was an 11-site, 6-month randomized
comparative effectiveness study that compared lithium, a classic mood
stabilizer, to quetiapine, a second-generation antipsychotic, each with
adjunctive personalized treatments (APTs [i.e., evidence-based, guide-
line-informed treatment based on illness course, treatment history, and
current symptomatology]) in bipolar disorder. For a detailed descrip-
tion of the study design see Nierenberg et al. (2014). The study protocol
was approved by the IRB and managed individually at the 11 sites.
Participants provided written informed consent before starting any
study-related procedure. The Bipolar CHOICE study was registered on
ClinicalTrials.gov (identifier: NCT01331304).
2.1. Participants
The sample of this study is diverse and generalizable. The Bipolar
CHOICE study was designed with limited inclusion and exclusion
criteria in order to maximize generalizability. Eligible patients diag-
nosed with bipolar disorder I or II in any symptomatic mood state
entered the study with at least mild symptoms of bipolar disorder
(Clinical Global Impressions-Bipolar Version [CGI-BP] score ≥3
(Spearing et al., 1997). Potential participants were excluded from the
study if they had any contraindication to lithium or quetiapine (e.g.,
pregnancy, prior hypersensitivity, severe renal disease, or lack of
treatment response after an adequate trial), were currently in crisis
such that hospitalization or more acute care was necessary, were
currently taking lithium or quetiapine, or were unable to comply with
study requirements. Data from the baseline assessment of enrolled
patients were used, but only patients presenting with a depressive
episode at study entry were included for the present study.
30
Journal of Affective Disorders 217 (2017) 29–33
2.2. Assessments
Clinical interviewers obtained demographic information (e.g., em-
ployment and disability status, household income, educational back-
ground, and marital status), family psychiatric history, number of
previous hospitalizations, suicide attempts, and age at illness onset.
2.2.1. Diagnosis and symptom severity
Lifetime and current diagnoses according to Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, Text Revision
(DSM-IV-TR) (American Psychiatric Association, 2000), including
bipolar disorder and other psychiatric comorbidities, were established
at the screening visit with the electronic Mini-International
Neuropsychiatric Interview (eMINI-PLUS) (Sheehan et al., 1998).
The eMINI-PLUS was also used to assess current suicidality.
Symptom severity was assessed by the CGI-BP and the Bipolar
Inventory of Symptoms Scale (BISS) (Bowden et al., 2007; Gonzalez
et al., 2008), a structured interview that yields an overall severity score
with subscales specific to mania and depression. The BISS also
identifies five domains of behavioral psychopathology (i.e., depression,
mania, psychosis, irritability and anxiety) (Thompson et al., 2010).
Items of the psychotic domain of the BISS were used to define the
presence of psychotic symptoms (i.e., itens 41-Persecutory Ideas; 42-
Delusions; 43-Hallucinations; and 44-Impaired Insight). Patients were
considered psychotic if a delusion or hallucination was definitely
present; that is, there was a score of 4 on item 41 (persecutory ideas),
a score greater than or equal to 2 on items 42 (delusions) or 43
(hallucinations), or a score of 3 or 4 on item 44 (impaired insight).
2.2.2. Functioning
Overall functioning was measured with the Longitudinal Interval
Follow-up Evaluation-Range of Impaired Functioning Tool (LIFE-
RIFT) (Leon et al., 2000). The LIFE-RIFT comprises an overall score
as well as four subscales characterizing the extent to which current
psychopathology impacts: (1) work (i.e., employment, household,
student); (2) relationships (i.e., spouse, children, other relatives,
friends); (3) overall life satisfaction; and (4) recreation. Higher LIFE-
RIFT scores indicate greater functional impairment.
2.3. Statistical analysis
Data were analyzed using SPSS 20.0. Univariate analyses were
performed using student t-tests for continuous variables with a normal
distribution and Mann-Whitney U-tests for continuous variables with
non-normal distribution. Categorical variables were compared using
the chi-square (χ2) test or Fisher's Exact test when indicated. To adjust
observed associations for depression severity, a multivariate analysis
was performed using a logistic regression model with psychosis being
the dependent variable. All variables for which a statistically significant
difference was observed in the univariate analyses were included as
predicting variables. The severity variable used in this model was the
depression subscale of the BISS. This subscale was selected because it
does not include the BISS itens that were used to define psychosis. All
tests were two-tailed and a p-value < 0.05 was considered statistically
significant, with no adjustment for multiple comparisons, given the
exploratory nature of these analyses.
3. Results
Three hundred and three patients (62.9%) out of the 482 total
sample presented with a major depressive episode at the time of
enrollment. There were more women (60.7%; n=184) than men and
the mean age was 39.45 ± 12.1 years. BD I was more frequent (64.7%;
n=196) than BD II (35.3%; n=107). Among the depressed patients, 32
(10.6%) also presented with psychotic symptoms. Paranoid delusion
was present in 2 patients (0.7%), any delusion in 17 patients (5.6%),
M.A. Caldieraro et al. Journal of Affective Disorders 217 (2017) 29–33

Table 1 Table 2
Demographic Characteristics (Psychotic vs. Nonpsychotic Bipolar Depression). Clinical and Functioning Differences Between Psychotic and Nonpsychotic Bipolar
Depression.
Psychotic Nonpsychotic
Depression Depression Psychotic Nonpsychotic p-value
n=32 n=271 Depression Depression
n=32 n=271
Female 19 (59.4) 165 (60.9) 0.869
Age 36.91 ± 13.4 39.75 ± 11.9 0.210 Bipolar I disorder 25 (78.1%) 171 (63.1%) 0.093
Marital status 0.036 Age at first depressive 14.81 ± 8.3 16.73 ± 7.8 0.194
Single/never married 22(68.8) 121(44.6) episode
Married or living as 6(18.8) 90(33.2) Age at first maniac 21.53 ± 11.8 20.18 ± 9.4 0.223
married episode
Separated/widowed 4(12.5) 50(22.1) Total number of 10(95) 21.5(41) 0.275
Educational 0.034 depressive episodes
background Total number of maniac 20(39) 20(79) 0.851
Less than High School 5(15.6) 12 (4.4) episodes
High School or GED 10(31.2) 56(20.7) BISS Overall 75.22 ± 17.6 54.86 ± 16.3 < 0.001
Some College 7(21.9) 75(27.7) BISS Depression 48.78 ± 11.7 39.51 ± 12.0 < 0.001
Tech School or 4(12.5) 37(13.7)
associates degree BISS domains
College diploma 3(9.4) 73(26.9) Depression 29.47 ± 7.1 24.86 ± 8.0 0.002
Graduate or 3(9.4) 18(6.6) Psychosis 4.91 ± 2.2 0.56 ± 0.9 < 0.001
professional degree Mania 17.78 ± 9.1 11.41 ± 8.6 < 0.001
Employed 6(18.8) 102(37.6) 0.035 Irritability 7.75 ± 3.5 6.14 ± 3.2 0.026
Household income 0.003 Anxiety 8.22 ± 3.3 6.14 ± 3.2 0.001
24,999 or less 21(70.0) 141(52.2) CGI BP-Severity of illness 5.13 ± 0.9 4.53 ± 0.8 < 0.001
25,000–49,999 9(30.0) 44(16.3) score
50,000–74,999 0(0.0) 38(14.1) Current Suicidality 0.045
75,000 or greater 0(0.0) 47(17.4) High 11 (34.4%) 40 (14.8%)
Moderate 4 (12.5%) 41 (15.1%)
Note: Statistics reported are n(%) for categorical variables and mean ± sd for continuous Low 16 (50.0%) 173 (63.8%)
variables. P values reported are based on χ2 test for categorical variables and t-test for None 1 (3.1%) 17 (6.3%)
continuous variables. History suicide 19 (59.4%) 100 (36.9%) 0.014
GED: General Education Development. attempts
History of psychiatric 17 (53.1%) 131 (48.3%) 0.609
hospitalizations
hallucinations in 22 patients (7.3%), and a delusional explanation for
his/her disorder in 3 patients (1.0%). Among the 32 patients with any Comorbid Conditions
psychotic symptom, 10 (31.3%) had only delusions, 11 (34.4%) had Panic Disorder 12 (37.5%) 63 (23.2%) 0.077
only hallucinations and 11 (34.4%) had both delusions and hallucina- (current)
Agoraphobia (current) 18 (56.2%) 95 (34.9%) 0.017
tions.
Social phobia (current) 12 (37.5%) 66 (24.4%) 0.018
We found no group difference in terms of sex and age, but a higher GAD (current) 13 (40.6%) 62 (22.9%) 0.028
proportion of depressed patients with psychotic symptoms were single OCD (current) 5 (15.6%) 26 (9.6%) 0.538
(68.8%) as opposed to patients without psychosis, who were more PTSD (current) 5 (15.6%) 31 (11.4%) 0.489
ADHD (current) 10 (31.2%) 61 (22.4%) 0.509
frequently married (33.2%) or had been married (i.e., divorced or
Any substance use 19 (59.4%) 170 (62.7%) 0.711
widowed) (22.1%). Educational background was also significantly disorder lifetime
different between groups, such that those who had not experienced
psychosis were more likely to have earned a college diploma than those LIFE-Rift
with psychosis. Psychotic patients were also less frequently employed Total 15.91 ± 3.4 14.44 ± 3.0 0.010
Work 4.34 ± 0.9 3.57 ± 1.3 < 0.001
and had lower household income (see Table 1).
Interpersonal 3.78 ± 1.4 3.70 ± 1.1 0.735
Current psychosis was present in 12.8% (n=25/196) of those with Relationship
BD I and in 6.5% (n=7/107) of those with BD II, but this difference was Satisfaction 3.81 ± 1.1 3.53 ± 0.9 0.097
not statistically significant (see Table 2). There was a tendency for an Recreation 3.97 ± 1.1 3.65 ± 1.1 0.110
earlier age of onset in individuals with psychosis, but the difference was
Note: Statistics reported are n (%) for categorical variables and mean ± sd for continuous
not statistically significant. There was also no statistically significant
variables, except Total number of depressive episodes and Total number of manic
difference in previous number of depressive or manic episodes, nor in episodes, reported as median (interquartile range). P values reported are based on χ2 test
number of previous hospitalizations. Patients with psychotic symptoms for categorical variables and t-test for continuous variables, except Total number of
presented with higher symptom severity overall as they had higher depressive episodes and Total number of manic episodes, when Mann-Whitney U-test
scores on CGI-BP as well as all of the BISS subscales compared to non- was used.
Abbreviations: BISS: Bipolar Inventory of Symptoms Scale; CGI BP: Clinical Global
psychotic depressed participants (see Table 2). The rate of high
Impressions-Bipolar Version scale; GAD: Generalized Anxiety Disorder; OCD: Obsessive-
suicidality, as assessed by the specific section of the eMINI-PLUS,
Compulsive Disorder; PTSD: Post-Traumatic Stress Disorder; ADHD: Attention Deficit
was more than double in those with psychosis (34.4% versus 14.8%), Hyperactivity Disorder; LIFE-RIFT: Longitudinal Interval Follow-up Evaluation-Range
and the prevalence of previous suicide attempt(s) was also higher in of Impaired Functioning Tool.
this group (59.4% versus 36.9%). Psychosis was also associated with
more anxiety disorder comorbidity, but there was no significant As some studies in unipolar depression require the presence of a
difference in family history of depression, bipolar disorder, suicide, delusion to define a psychotic episode (Meyers et al., 2009), we re-ran
psychosis, or substance use disorder (see Table 2). In regards to life the analysis considering as psychotic only the individuals presenting at
functioning, LIFE-RIFT total score was higher for those with psychosis, least one delusion (n=21). In this analysis, the proportion of BP I was
indicating worse functioning overall, but there was no significant significantly higher in those with psychosis (85.7% vs. 63.8%;
difference in interpersonal relationships, satisfaction, or recreational p=0.037). For the other variables, results were similar to that of the
domains. However, there was markedly worse functioning in the work original analysis.
domain for psychotic patients (Table 2).

31
M.A. Caldieraro et al.
In a logistic regression including variables significantly different
between the two groups (severity, marital status, educational back-
ground, employment status, suicidality, previous suicide attempts, total
LIFE-RIFT, and comorbidities), only severity (β=0.071; p < 0.001) and
marital status (β=1.11; p=0.018) were independently associated with
increased risk for psychosis. The BISS depression subscale was used as
the depression severity variable in this model.
4. Discussion
This was the first study aiming to compare psychotic and non-
psychotic bipolar depression in a generalizable sample. In spite of our
outpatient sample including a substantial number of patients with
bipolar II disorder, we found psychotic symptoms in approximately
11% of acute bipolar depressions, with psychotic depression being
associated with more severe symptoms, higher suicidality, more
comorbidities, and worse overall and work functioning.
This prevalence of psychosis in the current depressive episode is
similar to that of the only previous study on psychotic depression in
bipolar disorder (Benazzi, 1999). A study comparing BD I with BD II,
which also assessed patients during depressive episodes reported a
similar prevalence of psychosis in this group (Mantere et al., 2004).
The higher illness severity of patients with psychotic symptoms was
also described in the study from Benazzi. A new finding of this study
was that this increased severity was not only present in depressive and
psychotic domains, but was also associated with higher scores in all
BISS domains including mania, irritability and anxiety. This is further
highlighted by the higher comorbidity with agoraphobia, social phobia
and GAD in psychotic participants. These data indicate that all these
domains of symptoms must be explored when assessing a patient with
psychotic bipolar depression.
This was also the first study to report that in bipolar depression,
current suicidality was elevated in those with current psychosis. These
patients also presented a higher prevalence of previous suicide
attempt(s). These results are similar to what has been described for
unipolar depression (Meyers et al., 2009; Zalpuri and Rothschild,
2016) and are in accordance with two previous studies that reported a
positive association between psychosis and previous suicide attempts
in rapid cycling bipolar disorders (Gao et al., 2009) and other mood
disorders (Passos et al., 2016). However, these studies assessed for a
history of psychosis, rather than current psychosis and were not
restricted to patients in depressive episodes. This finding has clinical
implications, indicating that special attention to suicidality should be
given when assessing a patient with psychotic bipolar depression.
Bipolar disorder is a disabling condition (Ferrari et al., 2016), and
previous studies indicate that BD leads to work disability and un-
employment (Arvilommi et al., 2015; Boland et al., 2015; Peters et al.,
2016). The functioning and demographic results of this study suggest
that psychosis has a major impact in the disability of bipolar depres-
sion. The LIFE-RIFT results indicate worse current functioning in
those with psychotic symptoms, mainly attributable to dysfunction in
the work domain. The worse outcomes in education, employment,
income and interpersonal relationships indicate that this greater
dysfunction is not only acute. It seems likely that bipolar persons with
current psychotic symptoms have a more disabling disorder long-term.
The higher severity of depressive episodes and the worse function-
ing of the individuals presenting psychotic symptoms were not
unexpected. These findings are in accordance with clinical evidence
on psychotic disorders (Ozyildirim et al., 2010; Velthorst et al., 2016;
Waghorn et al., 2012) and unipolar depression with psychotic features
(Meyers et al., 2009). However, there are a scarcity of studies
addressing these topics in bipolar depression with psychosis.
In the multivariate analysis, only severity and marital status were
associated with increased risk for psychosis. This result reinforces that
psychotic symptoms are associated with more severe depressive
episodes. At the same time, significant differences observed in the
32
Journal of Affective Disorders 217 (2017) 29–33
univariate analysis were not maintained in this model. One possible
explanation is that most of the differences between the groups are
secondary to the higher depression severity in those with psychotic
symptoms. However, such relevant differences may not have been
observed in the model because the power of this study was limited by
the small number of patients with psychosis. New studies with larger
samples may be needed to evaluate if differences between psychotic
and nonpsychotic bipolar depression are only secondary to differences
in illness severity or some of them are independent of it.
This study has some limitations. The study included only out-
patients. However, this limitation impacts the results in a conservative
way, as including more severe cases of psychotic depression would
probably increase observed differences. Another limitation is the lack
of information about presence of psychotic symptoms in previous
mood episodes, so it is not possible to determine if psychotic episodes
tend to be recurrent in the same patient. The power of this study was
limited by the relatively small number of patients with psychosis
(N=32). Also, psychosis was not a primary outcome measure for the
Bipolar CHOICE study, and the data for these analyses were extracted
from the BISS.
In summary, we found that psychotic bipolar depressive episodes
were more severe than nonpsychotic episodes and associated with
more suicidality, more comorbidities and worse functioning. As future
analyses, we will examine treatment outcomes and the course of
psychotic symptoms in depressed patients from the Bipolar CHOICE
study cohort.
Role of funding source
This work was supported by the Agency for Healthcare Research
and Quality (AHRQ) [grant number 1R01HS019371-01]. This study
was funded by the Agency for Healthcare Research and Quality
(AHRQ), 1R01HS019371-01. AHRQ issued a request for applications,
approved and funded the study proposal, and provided oversight in
terms of on-time recruitment. They were not involved in design of the
study; conduct, collection, actual management, analysis, or interpreta-
tion of data; or preparation, review, or approval of manuscripts.
Acknowledgments
None.
References
Altamura, A.C., Buoli, M., Caldiroli, A., Caron, L., Cumerlato Melter, C., Dobrea, C.,
Cigliobianco, M., Zanelli Quarantini, F., 2015. Misdiagnosis, duration of untreated
illness (DUI) and outcome in bipolar patients with psychotic symptoms: a
naturalistic study. J. Affect. Disord. 182, 70–75. http://dx.doi.org/10.1016/
j.jad.2015.04.024.
American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition, Text Revision (DSM-IV-TR). American Psychiatric
Association.
Arvilommi, P., Suominen, K., Mantere, O., Valtonen, H., Leppämäki, S., Isometsä, E.,
2015. Predictors of long-term work disability among patients with type I and II
bipolar disorder: a prospective 18-month follow-up study. Bipolar Disord. 17,
821–835. http://dx.doi.org/10.1111/bdi.12349.
Benazzi, F., 1999. Psychotic versus nonpsychotic bipolar outpatient depression. Eur.
Psychiatry 14, 458–461.
Boland, E.M., Stange, J.P., Molz Adams, A., LaBelle, D.R., Ong, M.-L., Hamilton, J.L.,
Connolly, S.L., Black, C.L., Cedeño, A.B., Alloy, L.B., 2015. Associations between
sleep disturbance, cognitive functioning and work disability in Bipolar Disorder.
Psychiatry Res. 230, 567–574. http://dx.doi.org/10.1016/j.psychres.2015.09.051.
Bowden, C.L., Singh, V., Thompson, P., Gonzalez, J.M., Katz, M.M., Dahl, M., Prihoda,
T.J., Chang, X., 2007. Development of the bipolar inventory of symptoms scale. Acta
Psychiatr. Scand. 116, 189–194. http://dx.doi.org/10.1111/j.1600-
0447.2006.00955.x.
Dell'Osso, L., Pini, S., Tundo, A., Sarno, N., Musetti, L., Cassano, G.B., 2000. Clinical
characteristics of mania, mixed mania, and bipolar depression with psychotic
features. Compr. Psychiatry 41, 242–247. http://dx.doi.org/10.1053/
comp.2000.7432.
Ferrari, A.J., Stockings, E., Khoo, J.-P., Erskine, H.E., Degenhardt, L., Vos, T., Whiteford,
H.A., 2016. The prevalence and burden of bipolar disorder: findings from the Global
M.A. Caldieraro et al.
Burden of Disease Study 2013. Bipolar Disord. 18, 440–450. http://dx.doi.org/
10.1111/bdi.12423.
Fountoulakis, K.N., Young, A., Yatham, L., Grunze, H., Vieta, E., Blier, P., Moeller, H.J.,
Kasper, S., 2016. The international college of neuropsychopharmacology (CINP)
treatment guidelines for bipolar disorder in adults (CINP-BD-2017), Part 1:
background and methods of the development of guidelines. Int. J.
Neuropsychopharmacol.. http://dx.doi.org/10.1093/ijnp/pyw091.
Frankland, A., Cerrillo, E., Hadzi-Pavlovic, D., Roberts, G., Wright, A., Loo, C.K.,
Breakspear, M., Mitchell, P.B., 2015. Comparing the phenomenology of depressive
episodes in bipolar I and II disorder and major depressive disorder within bipolar
disorder pedigrees. J. Clin. Psychiatry 76, 32–38. http://dx.doi.org/10.4088/
JCP.14m09293.
Gao, K., Tolliver, B.K., Kemp, D.E., Ganocy, S.J., Bilali, S., Brady, K.L., Findling, R.L.,
Calabrese, J.R., 2009. Correlates of historical suicide attempt in rapid-cycling bipolar
disorder: a cross-sectional assessment. J. Clin. Psychiatry 70, 1032–1040.
Goes, F.S., Sadler, B., Toolan, J., Zamoiski, R.D., Mondimore, F.M., Mackinnon, D.F.,
Schweizer, B., Bipolar Disorder Phenome Group, Raymond Depaulo, J., Potash, J.B.,
2007. Psychotic features in bipolar and unipolar depression. Bipolar Disord. 9,
901–906. http://dx.doi.org/10.1111/j.1399-5618.2007.00460.x.
Goghari, V.M., Harrow, M., 2016. Twenty year multi-follow-up of different types of
hallucinations in schizophrenia, schizoaffective disorder, bipolar disorder, and
depression. Schizophr. Res. 176, 371–377. http://dx.doi.org/10.1016/
j.schres.2016.06.027.
Gonzalez, J.M., Bowden, C.L., Katz, M.M., Thompson, P., Singh, V., Prihoda, T.J., Dahl,
M., 2008. Development of the Bipolar Inventory of Symptoms Scale: concurrent
validity, discriminant validity and retest reliability. Int. J. Methods Psychiatr. Res.
17, 198–209. http://dx.doi.org/10.1002/mpr.262.
Leon, A.C., Solomon, D.A., Mueller, T.I., Endicott, J., Posternak, M., Judd, L.L.,
Schettler, P.J., Akiskal, H.S., Keller, M.B., 2000. A brief assessment of psychosocial
functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal interval
follow-up evaluation-range impaired functioning tool. J. Nerv. Ment. Dis. 188,
805–812.
Mantere, O., Suominen, K., Leppämäki, S., Valtonen, H., Arvilommi, P., Isometsä, E.,
2004. The clinical characteristics of DSM-IV bipolar I and II disorders: baseline
findings from the Jorvi Bipolar Study (JoBS). Bipolar Disord. 6, 395–405. http://
dx.doi.org/10.1111/j.1399-5618.2004.00140.x.
Meyers, B.S., Flint, A.J., Rothschild, A.J., Mulsant, B.H., Whyte, E.M., Peasley-Miklus,
C., Papademetriou, E., Leon, A.C., Heo, M., STOP-PD Group, 2009. A double-blind
randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo
for psychotic depression: the study of pharmacotherapy of psychotic depression
(STOP-PD). Arch. Gen. Psychiatry 66, 838–847. http://dx.doi.org/10.1001/
archgenpsychiatry.2009.79.
Mitchell, P.B., Wilhelm, K., Parker, G., Austin, M.P., Rutgers, P., Malhi, G.S., 2001. The
clinical features of bipolar depression: a comparison with matched major depressive
disorder patients. J. Clin. Psychiatry 62, 212–216.
Nierenberg, A.A., McElroy, S.L., Friedman, E.S., Ketter, T.A., Shelton, R.C., Deckersbach,
T., McInnis, M.G., Bowden, C.L., Tohen, M., Kocsis, J.H., Calabrese, J.R., Kinrys, G.,
Bobo, W.V., Singh, V., Kamali, M., Kemp, D., Brody, B., Reilly-Harrington, N.A.,
Sylvia, L.G., Shesler, L.W., Bernstein, E.E., Schoenfeld, D., Rabideau, D.J., Leon,
A.C., Faraone, S., Thase, M.E., 2016. Bipolar CHOICE (Clinical Health Outcomes
Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus
quetiapine for bipolar disorder. J. Clin. Psychiatry 77, 90–99. http://dx.doi.org/
10.4088/JCP.14m09349.
Nierenberg, A.A., Sylvia, L.G., Leon, A.C., Reilly-Harrington, N.A., Shesler, L.W.,
McElroy, S.L., Friedman, E.S., Thase, M.E., Shelton, R.C., Bowden, C.L., Tohen, M.,
Singh, V., Deckersbach, T., Ketter, T.A., Kocsis, J.H., McInnis, M.G., Schoenfeld, D.,
Bobo, W.V., Calabrese, J.R., Bipolar CHOICE Study Group, 2014. Clinical and
Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder
(Bipolar CHOICE): a pragmatic trial of complex treatment for a complex disorder.
Clin. Trials 11, 114–127. http://dx.doi.org/10.1177/1740774513512184.
Ozyildirim, I., Cakir, S., Yazici, O., 2010. Impact of psychotic features on morbidity and
course of illness in patients with bipolar disorder. Eur. Psychiatry 25, 47–51. http://
dx.doi.org/10.1016/j.eurpsy.2009.08.004.
33
Journal of Affective Disorders 217 (2017) 29–33
Pallaskorpi, S., Suominen, K., Ketokivi, M., Mantere, O., Arvilommi, P., Valtonen, H.,
Leppämäki, S., Isometsä, E., 2015. Five-year outcome of bipolar I and II disorders:
findings of the Jorvi Bipolar Study. Bipolar Disord. 17, 363–374. http://dx.doi.org/
10.1111/bdi.12291.
Passos, I.C., Mwangi, B., Cao, B., Hamilton, J.E., Wu, M.-J., Zhang, X.Y., Zunta-Soares,
G.B., Quevedo, J., Kauer-Sant'Anna, M., Kapczinski, F., Soares, J.C., 2016.
Identifying a clinical signature of suicidality among patients with mood disorders: a
pilot study using a machine learning approach. J. Affect. Disord. 193, 109–116.
http://dx.doi.org/10.1016/j.jad.2015.12.066.
Peters, A.T., West, A.E., Eisner, L., Baek, J., Deckersbach, T., 2016. The burden of
repeated mood episodes in Bipolar I Disorder: results from the National
Epidemiological Survey on alcohol and related conditions. J. Nerv. Ment. Dis. 204,
87–94. http://dx.doi.org/10.1097/NMD.0000000000000425.
Radaelli, D., Poletti, S., Gorni, I., Locatelli, C., Smeraldi, E., Colombo, C., Benedetti, F.,
2014. Neural correlates of delusion in bipolar depression. Psychiatry Res. 221, 1–5.
http://dx.doi.org/10.1016/j.pscychresns.2013.10.004.
Rosenthal, N.E., Rosenthal, L.N., Stallone, F., Dunner, D.L., Fieve, R.R., 1980. Toward
the validation of RDC schizoaffective disorder. Arch. Gen. Psychiatry 37, 804–810.
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.,
Hergueta, T., Baker, R., Dunbar, G.C., 1998. The Mini-International
Neuropsychiatric Interview (M.I.N.I.): the development and validation of a
structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin.
Psychiatry 59 (Suppl 20), S34–S57.
Solomon, D.A., Leon, A.C., Coryell, W.H., Endicott, J., Li, C., Fiedorowicz, J.G., Boyken,
L., Keller, M.B., 2010. Longitudinal course of bipolar I disorder: duration of mood
episodes. Arch. Gen. Psychiatry 67, 339–347. http://dx.doi.org/10.1001/
archgenpsychiatry.2010.15.
Spearing, M.K., Post, R.M., Leverich, G.S., Brandt, D., Nolen, W., 1997. Modification of
the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-
BP. Psychiatry Res. 73, 159–171.
Thompson, P.M., Gonzalez, J.M., Singh, V., Schoolfield, J.D., Katz, M.M., Bowden, C.L.,
2010. Principal domains of behavioral psychopathology identified by the Bipolar
Inventory of Signs and Symptoms Scale (BISS). Psychiatry Res. 175, 221–226.
http://dx.doi.org/10.1016/j.psychres.2009.04.017.
Tohen, M., Khalsa, H.-M.K., Salvatore, P., Vieta, E., Ravichandran, C., Baldessarini, R.J.,
2012. Two-year outcomes in first-episode psychotic depression the McLean-Harvard
First-Episode Project. J. Affect. Disord. 136, 1–8. http://dx.doi.org/10.1016/
j.jad.2011.08.028.
Tohen, M., Zarate, C.A., Hennen, J., Khalsa, H.-M.K., Strakowski, S.M., Gebre-Medhin,
P., Salvatore, P., Baldessarini, R.J., 2003. The McLean-Harvard First-Episode Mania
Study: prediction of recovery and first recurrence. AJP 160, 2099–2107. http://
dx.doi.org/10.1176/appi.ajp.160.12.2099.
Velthorst, E., Fett, A.-K.J., Reichenberg, A., Perlman, G., van Os, J., Bromet, E.J., Kotov,
R., 2016. The 20-year longitudinal trajectories of social functioning in individuals
with psychotic disorders. Am. J. Psychiatry. http://dx.doi.org/10.1176/
appi.ajp.2016.15111419.
Waghorn, G., Saha, S., Harvey, C., Morgan, V.A., Waterreus, A., Bush, R., Castle, D.,
Galletly, C., Stain, H.J., Neil, A.L., McGorry, P., McGrath, J.J., 2012. “Earning and
learning” in those with psychotic disorders: the second Australian national survey of
psychosis. Aust. NZ J. Psychiatry 46, 774–785. http://dx.doi.org/10.1177/
0004867412452015.
Zalpuri, I., Rothschild, A.J., 2016. Does psychosis increase the risk of suicide in patients
with major depression? A systematic review. J. Affect. Disord. 198, 23–31. http://
dx.doi.org/10.1016/j.jad.2016.03.035.
Zaninotto, L., Souery, D., Calati, R., Camardese, G., Janiri, L., Montgomery, S., Kasper,
S., Zohar, J., De Ronchi, D., Mendlewicz, J., Serretti, A., 2015. Dimensions of
delusions in major depression: socio-demographic and clinical correlates in an
unipolar-bipolar sample. Clin. Psychopharmacol. Neurosci. 13, 48–52. http://
dx.doi.org/10.9758/cpn.2015.13.1.48.
Østergaard, S.D., Bertelsen, A., Nielsen, J., Mors, O., Petrides, G., 2013. The association
between psychotic mania, psychotic depression and mixed affective episodes among
14,529 patients with bipolar disorder. J. Affect. Disord. 147, 44–50. http://
dx.doi.org/10.1016/j.jad.2012.10.005.