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Validity and reliability of a rating scale on

subjective cognitive deficits in bipolar disorder
(COBRA)
Article in Journal of Affective Disorders March 2013
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Research report

Validity and reliability of a rating scale on subjective cognitive decits

in bipolar disorder (COBRA)
Adriane R. Rosa a,b,e, Clara Mercade a, Jose Sanchez-Moreno a, Brisa Sole a,
Caterina Del Mar Bonnin a, Carla Torrent a, Iria Grande a, Gisela Sugranyes c, Dina Popovic a,
Manel Salamero d, Flavio Kapczinski b, Eduard Vieta a,n, Anabel Martinez-Aran a
a

Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM. Villarroel 170, Barcelona,
08036 Catalonia, Spain
b
Bipolar Disorders Program & INCT for Translational Medicine, Hospital de Clnicas de Porto Alegre, Universidade Federal do Rio Grande do Sul,
Ramiro Barcelos 2350, Porto Alegre, Rio Grande do Sul 90035903, Brazil
c
Department of Child and Adolescent Psychiatry and Psychology, Institut Clnic of Neurosciences, Hospital Clnic Universitari, Barcelona Villarroel, 170,
Barcelona 08036, Spain
d
Clinical Psychology. Department, Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona. Villarroel 170, Barcelona 08036, Spain
e
rio Unilasalle Rua Victor Barreto 2288, Canoas, RS, Brasil
Centro Universita

a r t i c l e i n f o

abstract

Article history:
Received 23 October 2012
Received in revised form
7 February 2013
Accepted 7 February 2013
Available online 14 March 2013

Background: Discrepancies between bipolar patients reports and neuropsychological testing have been
described and replicated. Unfortunately, no valid, specic, user-friendly, brief instrument is available to
measure cognitive decits as reported by these patients. The main aim of this study was to validate a
novel instrument named the cognitive complaints in bipolar disorder rating assessment (COBRA).
Second, we investigated the relationship between the COBRA, objective cognitive measures and illness
course variables.
Method: The total sample (N 215) included 91 bipolar disorder patients and 124 healthy controls. The
psychometric properties of the COBRA (e.g. internal consistency, concurrent validity, discriminative
validity, factorial analyses, ROC curve and feasibility) were analyzed. A complete neuropsychological
battery was used as objective cognitive assessment.
Results: The COBRA had one-factor structure with very high internal consistency (Cronbachs
alpha 0.913). A high convergent validity was indicated by a strong correlation with the Frankfurt
Complaint Questionnaire (ro 0.888, p o 0.001). Bipolar patients experienced greater cognitive complaints compared to control group suggesting a discriminative validity of the instrument. Signicant
correlations were found between the COBRA and some objective cognitive measures. Furthermore,
higher COBRA scores were associated with bipolar II subtype, residual depressive symptoms,
hypomanic episodes and total episodes.
Limitations: The cross-sectional design of the study, the inuence of medication and severity of patients
included.
Conclusions: The COBRA showed to be a useful instrument to assess overall cognitive complaints in
bipolar disorder with very satisfactory psychometric properties. Cognitive complaints were partially
correlated with memory and executive function measures and with issues that may increase the
subjective perception of cognitive decits, such as subthreshold depressive symptoms and number of
episodes.
& 2013 Elsevier B.V. All rights reserved.

Keywords:
Cognitive complaints
Cognitive impairment
Bipolar disorder

1. Introduction
Evidence has shown that patients with bipolar disorder experience
cognitive impairment both during acute episodes and remission
periods (Martinez-Aran et al., 2004; Robinson et al., 2006). In

Corresponding author. Tel.: 34932275401; fax: 34932279228.

E-mail addresses: evieta@clinic.ub.es, jsanche1@clinic.ub.es (E. Vieta).

0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2013.02.022

particular, patients have poorer performance in verbal memory and

executive function compared to healthy controls (Martinez-Aran
et al., 2004; Torrent et al., 2006). Furthermore neurocognitive decits
seem to affect negatively allostasis (Vieta et al., 2012), treatment
adherence (Lopez-Jaramillo et al., 2010; Martinez-Aran et al., 2009),
psychosocial functioning (Bonnin et al., 2010; Sole et al., 2012) and
may persist over time (Torrent et al., 2012); (Mora et al., 2012).
Nevertheless, there is a lack of consensus about the relevance in
investigating neurocognitive performance in patients with affective

30

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

disorders (Svendsen et al., 2012). In addition, a complete neurocognitive battery requires a longer time to administrate besides high
costs, which may limit its use, especially in the clinical practice.
Other available instruments, such as the Mini Mental State Examination (MMSE), commonly used in medicine to screen for dementia, are too basic to assess cognitive decits in psychiatric patients,
especially in young people. This instrument is not suitable to detect
cognitive impairment in patients with bipolar disorder with a
medium-high intellectual level. For this reason, the development
of brief instruments to assess cognitive decits reported by patients
is needed, especially in order to establish the relationship between
subjective cognitive complaints and objective cognitive decits. The
16-item Cognitive complaints in bipolar disorder rating assessment
(COBRA) is a self-reported instrument which allows us to assess
cognitive dysfunctions regarding the main decits experienced by
bipolar patients and reported in the literature. A better understanding about cognitive function could help clinicians to implement a more individualized treatment for bipolar patients.
Moreover, the validity of the subjective cognitive measures in
bipolar disorder is an important issue (Arts et al., 2011; Burdick
et al., 2005; Martinez-Aran et al., 2005). In this sense, most studies
have shown a relatively weak association between subjective
cognitive measures and neuropsychological test (Burdick et al.,
2005; Svendsen et al., 2012; van der Werf-Eldering et al., 2011).
Furthermore, subjective cognitive measures seem to be correlated
with depressive symptoms, suggesting that such measures may
reect depression severity rather than core cognitive impairment
(Svendsen et al., 2012; van der Werf-Eldering et al., 2011). The main
aim of the current study is to examine the psychometric properties
(including internal consistency, concurrent validity, discriminative
validity, factorial analyses, ROC curve and feasibility) of the COBRA.
We also investigate to what extent there is a relationship between
the COBRA, objective cognitive measures (assessed by neuropsychological battery) and the course of the illness.

2. Methods
2.1. Subjects
A total of 215 subjects participated in the study. We included 91
patients (age 1766 years) with DSM-IV bipolar I (n70, 76.92%)
and bipolar II (n21, 23.08%) and meeting criteria of remission
dened as a score r8 on the 17-Hamilton Depression Rating Scale
(HAM-D; (Bobes et al., 2003; Hamilton, 1960) and on the Young
Mania Rating Scale (YMRS; (Colom et al., 2002; Young et al., 1978)
for at least three months previous to the assessment. All patients
were enrolled in the Bipolar Disorders Program at the Hospital
Clinic of Barcelona, Spain (Vieta, 2011a).
One hundred twenty four volunteers who did not meet criteria
for any psychiatric disorder (according to the DSM-IV) were
included as healthy controls. We also made sure that controls
had no rst-degree relatives with bipolar disorder or other
psychiatric disorders. The healthy comparison group was
recruited from the general population within the catchment area
of the Hospital Clinic of Barcelona.
This study was approved by the Ethics Committee of the
Hospital Clinic of Barcelona. After a complete verbal description
of the study, all participants had written informed consent.
2.2. Assessments

 Clinical and socio-demographic assessment

Both the Structured Clinical Interview for DSM-IV (SCID) Axis I
and Axis II were administered to assess psychiatric disorders

(First et al., 1997). Socio-demographic, clinical and pharmacological data were collected via a structured interview with the
patient and by examination of clinical records. The 17-HAM-D
and the YMRS were administered to assess depressive and
manic symptoms, respectively.
 Subjective cognitive measures
(a) The COBRA was developed by the Bipolar Disorder Program
at the Hospital Clinic of Barcelona (Vieta, 2011b) in order to
detect the main daily cognitive complaints experienced by
bipolar patients. The initial version was built and tested in a
pilot study with bipolar patients and healthy controls
(unpublished). The nal version of the COBRA is a 16-item
self-reported instrument, which allows measure subjective
cognitive dysfunctions including executive function, processing speed, working memory, verbal learning and memory,
attention/concentration and mental tracking. All of items are
rated using a 4-point scale, 0never, 1sometimes,
2often, and 3 always (see Spanish and English versions
in Appendix 1). The COBRA total score is obtained when the
scores of each item are added up. The higher the score, the
more subjective complaints.
The linguistic adaptation of the COBRA started with a
document in English obtained by a translation/backtranslation method. The items not resulting in an appropriate wording equivalence with the original text were
analyzed by the team of investigators and the translators
until they agreed upon an appropriate expression. Subsequently, bilingual people evaluated the degree of equivalence between the Spanish original and the English version.
(b) The Frankfurt Complaint Questionnaire, which is an
unspecic but reliable instrument to assess cognitive
difculties in mental disorders, was also used to assess
subjective cognitive difculties (Cuesta et al., 1996).
 Validity and reliability assessment
a) Internal consistency reliability of the COBRA was assessed
by the Cronbachs coefcient a.
b) Concurrent validity for the COBRA was assessed in three ways:
(1) to examine the relationship between the COBRA and
Frankfurt Complaint Questionnaire; (2) to investigate the
association between the COBRA and objective cognitive measures (neuropsychological battery); (3) to investigate the possible correlations between the COBRA and course of the illness.
c) Validity as a discriminative measure to detect differences
between bipolar patients and healthy controls was analysed by non-parametric test.
d) The optimal point for the COBRA was determined by means
of ROC curve.
e) An exploratory factorial analysis by Principal Axis Factoring
method (Quartimax with Kaiser normalization) was performed to describe the internal structure of the COBRA.
f) Feasibility was described as the percentage of patients and
controls who did respond to the questionnaire in its entirety.
 Objective cognitive measures
a) Estimated premorbid IQ. This measure was estimated with
the WAIS-III vocabulary subtest (Weschler, 1997b).
b) Processing speed. It consisted on the two subtest of the
WAIS-III to estimate the processing-speed index: Digitsymbol coding and symbol search (Weschler, 1997b).
c) Executive function. This domain included tests of set
shifting, verbal uency, planning and response inhibition:

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

Wisconsin Card Sorting Test (WCST) (Heaton, 1981); Stroop

Colour-Word Interference Test (SCWT) (Golden, 1978); FAS
and animal naming (Controlled Oral Word Association Test)
(Benton and Hamsher, 1976); Trail Making Test-part B (TMT-B)
(Reitan, 1958); Rey Osterreith Copy Figure (ROCF) planning
(Rey, 1997).
d) Verbal learning and memory. This domain was assessed with
the California Verbal Learning Test (CVLT) (Delis et al., 1987)
and with logical memory (WMS-III) (Weschler, 1997a). Visual
memory was assessed with the ROCF (Rey, 1997).
e) Working memory and attention. The Trail Making Test-part
A (Reitan, 1958) was administered together with the three
subtests of the WAIS-III used to estimate the Working
Memory Index: arithmetic, digits forward and backwards,
letter-number sequencing (Weschler, 1997b).
This battery took from 90 to 120 min long, depending on the
participant. A 10 min break was done in the middle of the
assessment whenever the participant asked for it.
2.3. Statistical analysis
Statistical analysis was performed using SPSS for Windows
Version 18.0. internal consistency was assessed by the Cronbachs
alpha. Spearmans correlations coefcient was performed to
examine the possible relationship between the COBRA, Frankfurt
Complaint Questionnaire, neuropsychological tests and clinical
course of the illness. Group comparisons (patients and controls)
were made using non-parametric testes since the COBRA total
score did not show a homogeneous distribution. The rotation was
performed using the Quartimax method and ROC curve was used
to detect optimal point to discriminate patients and controls.

3. Results
The mean age of the patients was 41.83711.28 years and mean
age of the controls was 39.40711.59 years; p0.129). Fortyeight
(53.9%) patients and 62 (50%) of controls were men (p0.581).
Amongst the bipolar group, mood stabilizers were the most

31

commonly prescribed agents (78.6%), including lithium (48.9%),

valproate (14.1%) and carbamazepine (5.4%); 5.4% received lamotrigine; 43.8% atypical antipsychotics, 42.4% antidepressants and 29%
anxiolyticsedatives. Table 1 describes the main socio-demographic
and clinical characteristics of the sample.
3.1. Internal consistency
The internal consistency coefcient obtained was high with
Cronbachs alpha of 0.913 for the total scale suggesting that the
items are sufciently homogeneous. All items were also signicantly with the COBRA total score (minus that item) with a range
of 0.9030.911.
3.2. Associations between COBRA and Frankfurt Complaint
Questionnaire
A strong correlation was found between the COBRA and
Frankfurt Complaint Questionnaire scores indicating the concurrent validity of the instrument (ro 0.888, po0.001). See Fig. 1.
3.3. Associations between subjective and objective cognitive
measures
Spearman correlations were performed to assess relationship
between subjective and objective cognitive measures in both groups.
Signicant correlations were found between the COBRA and single
measures related to executive function (WCST perseverative errors,
p0.026), verbal learning and memory (CVLT total list A, p0.042;
CVLT cued delayed recall, p0.033; Rey Figure for visual memory,
p0.006), and working memory index (p0.0001) in the patients
group (see Table 2). As expected we did not nd any associations
between the COBRA and objective cognitive measures in the control
group. We performed correlation analyses between the COBRA and
an objective cognitive measure (e.g. working memory index) in
patients and control group. The COBRA variance is lower in the
control group than in patients, which may explain the low associations between subjective and objective cognitive measures in this
group (data not shown).

Table 1
Clinical and sociodemographic characteristics of the sample.

Age
Age at onset
Number of hospitalizations
Number of hypomanic episodes
Number of manic episodes
Number of depressive episodes
Number of mixed episodes
Number of total episodes
Number of suicidal attempts
Gender, male
University or post-graduate completed
Married
Current employed
Living alone
Depressive onset
Lifetime history of psychotic symptoms
Family history of affective disorders
Lifetime substance abuse
Life events
Rapid cycling
Seasonal pattern
Axis I comorbidity
Axis II comorbidity
Axis III comorbidity

Patients (n91) Mean (SD)

Controls (n 124) Mean (SD)

t student

41.83
31.38
1.68
3.52
2.42
6.13
0.78
12.33
0.71

(11.28)
(10.68)
(1.95)
(4.82)
(2.61)
(7.32)
(1.59)
(10.89)
(1.26)

39.4 (11.59)

0.053

0.129

(53.9)
(53.9)
(34.1)
(52.2)
(16.1)
(53.3)
(69.3)
(64.8)
(33.3)
(77.1)
(18.3)
(35.4)
(25)
(9.2)
(60.7)

62 (50)

0.321

0.581

48
48
31
47
14
48
61
57
28
64
15
29
22
8
51

32

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

Fig. 1. Concurrent validity of the COBRA. A Spearman correlation between COBRA and Frankfurt Complaints Questionnaire scores (ro 0.888, p o0.001).

Table 2
Associations between subjective and objective cognitive measures in both groups.

Estimated premorbid IQ

Patients COBRA
ro (p)

Controls COBRA
ro (p)

 0.150 (0.225)

0.101 (0.622)

0.278 (0.026)

 0.067 (0.747)

Executive functions
WCST
Perseverative errors
SCWT
Interference PD
TMT
Trail B
Rey gure planning

0.081 (0.806)

0.141 (0.493)

0.239 (0.058)
 0.222 (0.067)

0.247 (0.225)

Processing speed and attention

Processing speed index (IQ) (WAIS-III)

 0.202 (0.104)

 0.287 (0.155)

Working memory and attention

Working memory index (IQ) (WAIS-III)
TMT
Trail A
Verbal learning and memory
CVLT
List A (total)
Short free recall
Short cued recall
Delayed free recall
Delayed cued recall
Visual memory
Rey gure memory

 0.437 (0.0001)
0.170 (0.173)

 0.251
 0.159
 0.185
 0.241
 0.261

(0.042)
(0.199)
(0.134)
(0.050)
(0.033)

 0.327 (0.006)

 0.204 (0.318)
0.258 (0.203)

 0.349
 0.234
 0.086
 0.079
0.02

(0.080)
(0.251)
(0.277)
(0.700)
(0.993)

0.029 (0.887)

Table 3
The value of Spearmans correlation coefcients between COBRA and course of
bipolar disorder.
COBRA total score (n 91), ro (p)
Age
Age at onset
Number of hospitalizations
Number of hypomanic episodes
Number of manic episodes
Number of depressive episodes
Number of mixed episodes
Number of total episodes
Number of suicidal attempts
17-HAM-D
YMRS

0.175
 0.035
 0.079
0.267
 0.180
0.204
0.194
0.240
0.069
0.297
 0.028

(0.104)
(0.744)
(0.457)
(0.015)
(0.091)
(0.058)
(0.079)
(0.024)
(0.558)
(0.006)
(0.796)

patients with less subjective cognitive complaints were currently

working (F 13.384, po0.001), had higher educational level (F
5.859, p 0.018) and less lifetime substance abuse (F6.506,
p0.013) than those with more subjective cognitive complaints.

3.5. Validity as a discriminative measure to detect differences

between bipolar patients and healthy controls
Bipolar patients experienced higher COBRA total score (16.697
9.80) than healthy controls (8.6775.30; t7.01; po0.001).

Spearmans correlations (ro).

3.6. ROC curve

3.4. Associations between subjective cognitive measures and course
of the illness
The COBRA was also correlated with hypomanic episodes
(ro0.267 p0.015), total episodes (ro0.240. p0.024) and
residual depressive symptoms (ro0.297. p0.006) (see Table 3).
Bipolar II patients experienced more subjective complaints than
subjects with bipolar I disorder (F13.284, po0.001). Furthermore,

We analyzed the scales discriminative capacity between

patients and controls by means of the diagnostic performance
or ROC curve. The area under the curve was 0.748. 95% CI: (0.679
0.816) which being close to 1 indicates a good capacity. The
discriminative capacity analysis indicates that a score of 10
obtains the best balance between sensitivity (68.1%) and specicity (68.5%). See Fig. 2.

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

33

Fig. 2. ROC curve between patients and controls. The area under the curve was 0.748. 95% CI: (0.6790.816). The cut-off point 10 indicates the best balance between
sensitivity (68.1%) and specicity (68.5%).

4. Discussion

Table 4
Factorial loading on the COBRA.
Factor
1
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item
Item

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16

0.781
0.775
0.767
0.72
0.679
0.675
0.661
0.658
0.642
0.585
0.58
0.524
0.519
0.504
0.5
0.478

0.514

0.472

Extraction method: principal axis factoring (quartimax

rotation).

3.7. Factorial analysis

The study of the internal structure of the COBRA, after rotation
(using Quatrimax method) determined a two-factor structure as
shown in Table 4. However, as only two items were loaded in the
second-factor and their values were very closer of the rst-load,
we considered one-factor structure which was responsible for
43.77% of the total variance.

3.8. Feasibility
Finally, the results showed a high feasibility of the COBRA
since that the totality of participants answered all items of the
instrument.

The COBRA showed satisfactory psychometric properties with

very high internal consistency and convergent validity as indicated
by a signicant correlation with the Frankfurt Complaint Questionnaire. As expected, the COBRA total score was higher in patients
compared to healthy controls suggesting the discriminative validity of
the instrument. Furthermore, the COBRA had one-factor structure
which means that patients tend to perceive their decits as a global
cognitive dysfunction rather than to discriminate decits in specic
cognitive domains. One of the advantages of the COBRA over other
instruments is because it was specially designed to assess cognitive
problems related to bipolar patients. In contrast, other instruments
like FCQ have some items such as 1 or 18 which are related to
psychotic features and sometimes difcult to understand by many
bipolar patients. Therefore, 16-item COBRA seems to be a useful
instrument to assess cognitive complaints in bipolar disorder; and it
is ready available for its use in both, clinical practice and research
settings.
We also found signicant correlations between the COBRA and
some neuropsychological tests, particularly, in single measures
related to executive function, working memory, verbal and visual
memory. Studies assessing the relationship between subjective and
objective cognitive measures have shown controversial results (Arts
et al., 2011; Burdick et al., 2005; van der Werf-Eldering et al., 2011).
For instance, a recent research in bipolar patients did not show any
association between the Cognitive Failure Questionnaire (CFQ) and
objective neurocognitive battery, except for CFQ memory for names
and speed of processing information (van der Werf-Eldering et al.,
2011). Arts et al. (2011) showed that higher total CFQ scores were
signicantly associated with poor performance on basic information
processing and selective attention areas (Arts et al., 2011). Burdick
et al. (2005) did not nd relationship between total CFQ scores and
objective neurocognitive measures. However, the Cognitive Difculties Scale (CDS) was positively correlated with a CVLT short-term
recall which indicates that a better performance on the CVLT short
delayed recall was associated with more cognitive complaints. Taken
together all these ndings suggest that self-reported instruments may

34

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

be partially correlated with objective neurocognitive measures in

bipolar disorder, given that some subjective cognitive measures seem
not to be congruent with results obtained by a neuropsychological
assessment. Some cognitive complaints are related to biographical
memories which are not commonly measured by traditional neurocognitive testing. Moreover, social cognition may be impaired in
bipolar disorder but it is not generally assessed in these patients.
Probably, cognitive complaints are referred to subjective experience
of general cognitive problems that are not well characterized when
reported by patients (e.g. memory problems). Furthermore, factors
related to the course of the illness may also contribute to the partial
association between both objective and subjective cognitive measures. In this regard, duration of the illness, chronicity, subclinical
symptoms, relapses, psychotic symptoms, hospitalizations, comorbid
conditions, insight and anosognosia, as well as medication, among
other variables, could act as mediators or confounders in this
relationship between subjective and objective cognitive decits.
Actually, some bipolar patients are not aware of their cognitive
decits but show signicant impairment in neurocognitive testing
and impact on daily functioning. These difculties are generally
reported by relatives and observed by the clinician (Goldberg and
Chengappa, 2009; Martinez-Aran et al., 2005; Schouws et al., 2012).
Hence, the association between subjective and objective cognitive
decits is complex, and depressive symptoms may be one of the
mediators, but not the only one.
The results of the present study show a negative correlation
between cognitive complaints, work situation and educational
level, meaning that patients with less cognitive complaints were
more likely to have higher education level and be employed.
These ndings are consistent with neurocognitive functioning
studies which have pointed out a strong association between
cognitive impairment and poor overall functioning (Bonnin et al.,
2010;Martino et al., 2011;Tabares-Seisdedos et al., 2008). More
specically, verbal memory decits were identied as a good
predictor of functional impairment. Patients with more difculties in remembering long-term information seem to have more
problems to maintain their interpersonal relationships as well as
occupational functioning (Martinez-Aran et al., 2009). Considering that cognition plays a critical role on psychosocial functioning,
and that subjective cognitive dysfunctions may also be related to
functional impairment, the COBRA could be used as a proxy of
psychosocial functioning in bipolar disorder.
Interestingly, we found that subjects with bipolar II disorder
experienced greater cognitive complaints than those with bipolar I
subtype. In addition, subjective cognitive complaints were associated
with higher number of hypomanic and total episodes. It has well
known that bipolar II disorder is associated with more persistent
subclinical depressive symptoms (Judd et al., 2003), longer depressions (Pallanti et al., 1999) and greater number of depressive episodes
(Vieta et al., 1997), which may contribute to greater cognitive
complaints observed in this population (Sole et al., 2011). It suggests
that this subgroup of patients (e.g. bipolar II patients with depressive
symptoms and higher number of episodes) represents a population at
risk to experience more cognitive complaints which, in turn, can
affect psychosocial functioning. Therefore, a better understanding of
nature and extent of cognitive dysfunctions is especially relevant as
the implementation of cognition targeted treatments would help to
improve functioning (Fuentes-Dura et al., 2012; Martinez-Aran et al.,
2011).
As expected our results showed that bipolar patients with subclinical depressive symptoms tend to overestimate their cognitive
difculties indicating that there is a trend toward increased subjective
cognitive complaints alongside increased depressive symptomatology. Many studies have argued the inuence of depressive symptoms
on cognition in bipolar patients, especially, when it is assessed by the
self-reported instruments (Burdick et al., 2005; Miskowiak et al.,

2012; Svendsen et al., 2012; van der Werf-Eldering et al., 2011). Using
a multiple regression analysis, depressive severity was identied as a
potential predictor for subjective cognitive dysfunction, assessed by
the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), in a bipolar sample (Svendsen et al., 2012).
Another independent study showed that higher CPFQ total score was
signicantly correlated with mood symptoms (depression and manic)
as well as with anxiety (Miskowiak et al., 2012). Although emerging
data suggest that neuropsychological decits are an inherent feature
of bipolar disorder given that it occurs across mood states (MartinezAran et al., 2004;Torrent et al., 2007), a recent research found that
patients with subthreshold depressive symptoms are more impaired
in verbal learning than asymptomatic patients, using more restrictive
euthymia criteria (Bonnin et al., 2012), although no other differences
were found between group with respect to the remaining cognitive
measures. Anyway, these ndings highlight the potential negative
impact of subclinical depressive symptoms on objective but more
specically on subjective cognitive dysfunctions. An explanation may
have to do with the fact that depressed patients tend to underestimate their capacities and overestimate their decits.
The current study has some limitations. First, all patients were
recruited from a tertiary hospital where participants tend to present
more severe symptoms, and may not be readily generalized to the
wider population of subjects with bipolar disorder. Second, since our
patients were on pharmacological treatment, we cannot discount the
effects of drugs on objective and subjective cognitive measures.
Medication is likely to have an impact on subjective and objective
cognitive performance (Torrent et al., 2011; Videira et al., 2012). Some
psychometric properties such as testretest reliability and sensitive to
change of the COBRA were not performed, which should be investigated in follow-up studies. We should further analyze whether
subjective cognitive complaints may predict cognitive performance
in the long term (Arts et al., 2011). And despite our strict denition of
euthymia, cognitive complaints should be assessed when the patient
is in full remission, because subclinical symptoms may increase the
risk of experiencing subjective cognitive difculties. Psychoeducation
about cognitive decits and the potential role of clinical and pharmacological factors on cognition could be helpful to address this
common problem reported by patients in clinical practice.
In conclusion, the COBRA is a brief 16-item, self-reported instrument, which allows us to investigate cognitive dysfunctions focusing
on executive function, processing speed, working memory, verbal
learning and memory, attention/concentration and mental tracking
which are the main cognitive decits experienced by bipolar patients.
The instrument discriminates cognitive function between patients
and controls showing that a cut-off point higher 10 supports the
presence of cognitive impairment. Subjective cognitive measures
were partially correlated with some objective cognitive assessment
(e.g. executive function and memory tasks) and with poor course of
bipolar illness. Even though self-reports may be somehow biased, we
should take into consideration the patients view of cognitive problems through an instrument specically addressed to the difculties
commonly reported by bipolar patients in both clinical practice and
investigation. Subjective cognitive complaints do not always correspond to objective cognitive impairment. However, a neuropsychological battery, performed by a neuropsychologist, is required to
conrm cognitive decits. A longitudinal study including both objective and subjective assessments, as measured with the COBRA, may
greatly contribute to the knowledge about the clinical relevance and
outcome of cognitive complaints in bipolar disorder.
Author disclosure
Dr. Martinez-Aran has served as speaker or advisor for the
following companies: Bristol Myers-Squibb, Otsuka, Pzer, research
funding from the Spanish Ministry of Science and Innovation.

A.R. Rosa et al. / Journal of Affective Disorders 150 (2013) 2936

Professor Vieta has received research grants and served as

consultant, advisor or speaker for the following companies: Almirall,
Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Forest Research
Institute, Geodon Richter, Glaxo-Smith-Kline, Janssen-Cilag, Jazz,
Lundbeck, Merck, Novartis, Organon, Otsuka, Pzer Inc, SanoAventis, Servier, Solvay, Schering-Plough, Takeda, United Biosource
Corporation, and Wyeth, research funding from the Spanish
Ministry of Science and Innovation, the Stanley Medical Research
Institute and the 7th Framework Program of the European
Union.
Dra. Dina Popovic has served as speaker for the following
companies: Bristol Myers-Squibb and Merck Sherp & Dohme.
Dra. Iria Grande has served as speaker for Astra-Zeneca.
Role of funding source
This work was supported by grants from the Centro de Investigacion en Red de
Salud Mental, CIBERSAM.
Conict of interest
No conict declared.
Acknowledgements
Adriane R Rosa thanks the support by CNPq, Programa Ciencia sem Fronteiras
(bolsa Jovem Talento), Brazil.

Appendix 1. Spanish version of COBRA.

Escala de quejas cognitivas en el trastorno bipolar (COBRA)
1. Le cuesta recordar los nombres de las personas?
2. Tiene dicultades para encontrar objetos de uso habitual
(llaves, gafas, relojy)?
3. Tiene problemas para recordar situaciones que han sido
importantes para usted?
4. Es difcil para usted situar en el tiempo dichos
aconte-cimientos?
5. Le cuesta concentrarse en la lectura de un libro, diario,y?
6. Le resulta difcil recordar lo que ha ledo o le han dicho
recientemente?
7. Tiene la sensacion de que no acaba lo que comienza?
8. Va mas lento para hacer el trabajo del da a da?
9. Se ha desorientado alguna vez en la calle?
10. Cuando le recuerdan alguna conversacion o comentario,
tiene la impresion que es la primera vez que escucha esa
informacion?
11. Le cuesta en ocasiones encontrar las palabras para expresar
sus ideas?
12. Se distrae facilmente?
13. Le resulta complicado hacer calculos mentales sencillos?
14. Tiene la impresion de perder el hilo de la conversacion?
15. Ha observado si le resulta difcil aprender informacion
nueva?
16. Le cuesta mantener su atencion en alguna tarea durante
mucho rato?
0.
1.
2.
3.

Nunca
A veces
Frecuentemente
Siempre

English version of COBRA

Cognitive complaints in bipolar disorder rating assessment
(COBRA)
1. Do you have difculties to remember peoples names?
2. Do you have difculties to nd objects of daily use (keys,
glasses, wristwatchy)?

35

3. Do you nd it difcult to remember situations that were

important to you?
4. Is it hard for you to place important events in time?
5. Do you nd it hard to concentrate when reading a book or a
newspaper?
6. Do you have problems recalling what you have read or have
been told recently?
7. Do you have the feeling that you do not nish what
you begin?
8. Does it take you longer than normal to complete your
daily tasks?
9. Have you ever felt disoriented in the street?
10. When people remind you of a conversation or a comment you
heard, do you get the impression that it is the rst time you
hear it?
11. Is it sometimes difcult for you to nd the words to express
your ideas?
12. Are you easily distracted?
13. Do you nd it hard to do simple mental calculations?
14. Do you get the impression that you cannot follow a
conversation?
15. Have you noticed that you nd it difcult to learn new
information?
16. Do you struggle to keep focused on a particular task for a
long time?
0.
1.
2.
3.

Never
Sometimes
Often
Always

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