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ORIGINAL RESEARCH

published: 26 April 2019


doi: 10.3389/fpsyt.2019.00253

The Relationship Between Cognitive


Dysfunction and Symptom
Dimensions Across Schizophrenia,
Bipolar Disorder, and Major
Depressive Disorder
Yue Zhu 1,2, Fay Y. Womer 3, Haixia Leng 1,2, Miao Chang 1,2,4, Zhiyang Yin 1,2, Yange Wei 1,2,
Qian Zhou 1,2,5, Shinan Fu 1,2, Xin Deng 1,2, Jing Lv 1,2, Yanzhuo Song 1,2, Yinzhu Ma 1,2,
Xinyu Sun 1,2, Jing Bao 1,2, Shengnan Wei 1,2, Xiaowei Jiang 1,2, Shuping Tan 6,
Yanqing Tang 1,2,7* and Fei Wang 1,2,4*
Edited by: 1Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China, 2 Brain Function
Błażej Misiak, Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China, 3 Department of Psychiatry,
Wroclaw Medical University, Washington University School of Medicine, St Louis, MO, United States, 4 Department of Radiology, The First Affiliated
Poland Hospital of China Medical University, Shenyang, China, 5 Shanghai Mental Health Center, Shanghai, China, 6 Center for
Reviewed by: Psychiatric Research, Beijing Huilongguan Hospital, Beijing, China, 7 Department of Gerontology, The First Affiliated Hospital
Ernest Marek Tyburski, of China Medical University, Shenyang, China
University of Szczecin,
Poland
Kathryn Eve Lewandowski,
Background: Cognitive dysfunction is considered a core feature among schizophrenia
McLean Hospital, (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant
United States literature comparing cognitive dysfunction among these disorders, the relationship
*Correspondence: between cognitive dysfunction and symptom dimensions remains unclear. The study aims
Fei Wang
fei.wang@cmu.edu.cn are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship
Yanqing Tang between symptom domains and cognitive function across SZ, BD, and MDD.
tangyanqing@cmu.edu.cn
Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and
Specialty section: 249 healthy controls (HC)] were included in the study. One hundred eighty participants
This article was submitted to
(59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus
Schizophrenia,
a section of the journal Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD,
Frontiers in Psychiatry and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed
Received: 24 January 2019 the Brief Psychiatric Rating Scale (BPRS).
Accepted: 02 April 2019
Published: 26 April 2019 Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective
Citation: symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and
Zhu Y, Womer FY, Leng H, “noncooperation”) and found cognitive dysfunction in all of the participant groups
Chang M, Yin Z, Wei Y, Zhou Q,
Fu S, Deng X, Lv J, Song Y, Ma Y, with psychiatric disorders. Negative/disorganized symptoms were the most strongly
Sun X, Bao J, Wei S, Jiang X, associated with cognitive dysfunctions across SZ, BD, and MDD.
Tan S, Tang Y and Wang F
(2019) The Relationship Between Conclusions: Our findings suggest that cognitive dysfunction severity relates to the
Cognitive Dysfunction and negative/disorganized symptom domain across SZ, BD, and MDD, and negative/
Symptom Dimensions Across
Schizophrenia, Bipolar Disorder, disorganized symptoms may be an important target for effective cognitive remediation in
and Major Depressive Disorder. SZ, BD, and MDD.
Front. Psychiatry 10:253.
doi: 10.3389/fpsyt.2019.00253 Keywords: schizophrenia, bipolar disorder, major depressive disorder, symptom, cognitive function

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Zhu et al. Cognition, Symptom and Psychiatric Disorders

INTRODUCTION MATERIALS AND METHODS


Schizophrenia (SZ), bipolar disorder (BD), and major depressive Participants
disorder (MDD) have long been viewed as distinct disorders A total of 716 participants were included in the study: 262 with
based on differing clinical presentations (1); however, there SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HCs).
is substantial evidence suggesting that these disorders share Patients were recruited from inpatient and outpatient services
pathophysiological and clinical manifestations (2, 3). Moreover, in the Department of Psychiatry at the First Affiliated Hospital,
studies have shown co-aggregation of the three disorders in risk China Medical University and Shenyang Mental Health Center.
genes (4, 5), high familial risk (6), shared neurobiological and HC participants were recruited from the local community of
neuropsychological features (7), and overlapping syndromes that Shenyang using advertisements.
challenge existing classification criteria (8). Consequently, it has All participants were aged between 18 and 60 years old.
been proposed that SZ, BD, and MDD lie along a continuum Participants with SZ, BD, or MDD were diagnosed according
of neuropsychiatric illness, rather than represent three separate to Diagnostic and Statistical Manual of Mental Disorders-IV-
disorders (3, 9). Text Revision (DSM-IV-TR) standards, and the diagnoses were
Cognitive dysfunction is a core feature across SZ, BD, and confirmed by two trained psychiatrists using the Structured
MDD (10–12); however, studies of cognition across these Clinical Interview for DSM-IV Axis I disorders (SCID-I). HC
diagnoses have yielded mixed results (13). Increasingly, studies participants did not have current or life Axis I disorders and
have noted similar cognitive patterns and profiles in SZ, BD, any first-degree relatives with a history of Axis I disorders.
and MDD (14–16). To further investigate this theory, cognitive Participants were excluded for the following: concomitant major
function appears to be a relatively stable intermediate phenotype medical disorder, neurological disease or head injury with loss of
that may provide insight into the potential link between SZ, consciousness, and/or substance/alcohol abuse or dependence.
BD, and MDD (17, 18). This is further supported by extensive This study was approved by the Medical Research Ethics
literature implicating a continuum of cognitive dysfunction Committee of the China Medical University in accordance
severity based on severity of neuropsychiatric illness (15, 19, with the Declaration of Helsinki. All participants gave written
20). Interestingly, continuum models have also been proposed informed consent, or the parents or legal guardian for participants
for psychosis, reflecting shared dimensions of psychopathology <18 years, after receiving a detailed description of the study.
across SZ and mood disorders (10, 21).
Studies have examined the relationship between cognitive
deficits and symptom dimensions in psychiatric disorders; Measures
however, we are not aware of previous studies that examined All patients completed the BPRS-18 (29) to assess current
this relationship across SZ, BD, and MDD. Further, prior studies psychopathology.
have focused on the primary symptoms that distinguish SZ, Cognitive function was assessed in a subset of patients and HC
BD, and MDD from each other, limiting direct comparison of using the following: 1) MATRICS Consensus Cognitive Battery
psychopathology across SZ, BD, and MDD (22, 23). (MCCB) (30) [the battery is composed of 10 subtests across
The Brief Psychiatric Rating Scale (BPRS) is a very useful seven domains, including a) Speed of Processing: Trail Making
measure for psychopathology dimensions across SZ, BD, and Test-Part A (TMT-A), Symbol Coding, and Category Fluency; b)
MDD. It covers a broad range of symptom domains with efficient Working Memory (WM): Visual WM (Spatial Span) and Verbal
and valid assessment of symptom severity (24). While the BPRS WM (Letter-Number Span); c) Verbal Learning: Hopkins Verbal
is generally used to assess SZ and other psychotic disorders (25, Learning Test-Revised (HVLT-R); d) Visual Learning: Brief
26), it can also be used to analyze the factor structure in mood Visuospatial Memory Test-Revised (BVMT-R); e) Reasoning and
disorders (27). Exploratory factor analysis (EFA) identifies Problem Solving: Mazes; f) Attention: Continuous Performance
the underlying structure of a large variable set such as the Test-Identical Pairs version (CPT-IP), which measures the mean
BPRS. The structure and associated factors from EFA likely d’ score among the three conditions; and (g) Social Cognition:
reflect physiological and pathophysiological mechanisms (28). The Mayer–Salovey–Caruso Emotional Intelligence Test
Therefore, using the EFA of BPRS across SZ, BD, and MDD (MSCEIT); 59 SZ, 23 BD, 24 MDD, and 74 HC subjects completed
within the context of the same study would present patients their the MCCB] and 2) Wisconsin Card Sorting Test (WCST) (31).
own psychopathological characters, and provide a novel way to A computerized version of the WCST was given. The WCST
help us better understand complex psychiatric disorders better evaluates executive function and provides subscores as follows:
than categorical approaches alone. correct responses (CR), categories completed (CC), total errors
The study aims are a) to identify the factor structure of the (TE), perseverative errors (PE), and non-perseverative errors
BPRS-18 and b) to examine the relationship between symptom (NPE). Eighty-five SZ, 89 BD, 90 MDD, and 243 HC subjects
domains and cognitive function across SZ, BD, and MDD. We completed the WCST. There were 137 SZ, 11 BD, and 11 MDD
hypothesized that cognitive dysfunction are present across SZ, without cognitive test. This study included these patients used to
BD, and MDD, relative to healthy controls, and that negative/ assess psychopathology.
disorganized symptoms correlate with cognitive dysfunction For each participant, clinical and cognitive assessments were
severity. completed within 1 week.

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Zhu et al. Cognition, Symptom and Psychiatric Disorders

Statistical Analysis differed in duration of illness, age of first episode, first episode
ANOVAs (analyses of variance) or chi-square tests were used status, and medication status (Table 1).
to examine participants’ demographic characteristics (age and
sex) and clinical characteristics (duration of illness, age of first Exploratory Factor Analysis
episode, first episode, and medication status) accordingly. The sample size (n = 467) of our study was above the minimum
EFA was performed for BPRS scores in the patient groups recommended for EFA (n > 150). Further, the Kaiser–Meyer–
only. Orthogonal rotation was accomplished using the Varimax Olkin value of our study was 0.783, which exceeds the
method. The number of factors retained was determined based minimum recommended value (33). Importantly, Bartlett’s test
on eigenvalues >1, and the numbers were confirmed by the for sphericity was significant [X2 (153) = 2222.292, P < 0.001].
screen plot cutoff point. In order to accurately interpret the factor As such, all indicators support the suitability of the study’s data
structure and contents, we assumed that there was only a loading for EFA.
of more than 0.30 for any given variable to be significant (32). There were five eigenvalues greater than 1.0. Furthermore,
ANOVA and LSD’s post hoc analysis were used to compare the there was a clear change in the slope of the eigenvalue plot
factor structure scores and total score of BPRS among patient after the fifth factor, which determined the number of factors
groups (SZ, BD, and MDD). we computed. After Varimax rotation, we identified five
Cognitive measures (MCCB and WCST) were analyzed using interpretable and clinically relevant factors that captured 58.41%
ANCOVA (analyses of covariance) and LSD’s post hoc analyses, of the rotated variance. All of the BPRS-18 items were included
with sex, age, and years of education as covariates. For the MCCB, in the EFA. Table 2 lists the five resulting symptom factor
raw scores were used for each subtest. structures and their item loadings with absolute values greater
Partial correlation was used to determine the relationship than 0.30.
between BPRS EFA factor scores and cognitive measures in patient The BPRS EFA factors are as follows: 1) “affective symptoms”
group as a whole and separately, after controlling for sex and age. (includes depression, anxiety, guilt, tension, and somatic
False discovery rate correction was used for multiple comparisons. concerns), 2) “psychosis” (includes unusual thought content,
Based on previous correlation analyses, we then used multiple suspiciousness, hostility, and hallucinations), 3) “negative/
regression analyses to examine the effects of clinical symptom disorganized symptoms” (includes emotional withdrawal,
scores on cognitive outcomes after accounting for the above blunted affect, motor retardation, conceptual disorganization, and
demographic and clinical characteristics (diagnosis, duration of disorientation), 4) “activation” (includes excitement, mannerisms
illness, age of first episode, first episode, and medication). and posturing, and grandiosity), and 5) “noncooperation”
Significance was set at P < 0.05 (two-tailed) for all tests. All (consists only of uncooperativeness).
analyses were performed using SPSS 22.0. Total scores and factor scores of BPRS were significantly
different among the patient groups. Post hoc analysis revealed
that the BD and MDD groups significantly differed from the
RESULTS SZ group in BPRS total score and EFA factor scores of “affective
symptoms,” “psychosis,” “negative/disorganized symptoms,” and
Demographic Data of Participants “noncooperation.” There were no significant differences between
There were significant differences in age and sex among the SZ, BD and MDD groups. There were significant differences in
BD, MDD, and HC groups. Patient groups also significantly “activation” scores between SZ, BD, and MDD (Figure 1).

TABLE 1 | Demographic and clinical characteristics of schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and healthy controls (HC).

SZ BD MDD HC F/χ2 values P values


N = 262 N = 104 N = 101 N = 249

Demographic characteristics
Age 34.40 (11.09) 30.06 (9.88) 32.37 (9.26) 33.52 (11.69) 2.871a 0.036
Sex, Female 152 (58.0%) 64 (61.5%) 82 (81.2%) 154 (61.8%) 18.652a 0.001
Years of Education 11.74 (3.21) 13.29 (3.21) 13.11 (3.05) 14.43 (3.56) 27.483a <0.001
Clinical characteristics
Duration of Illness, Monthsc 71.98 (86.19) 59.02 (66.54) 23.98 (45.45) – 12.262b <0.001
Age of First Episodec 26.21 (8.46) 25.34 (9.23) 29.43 (10.10) – 5.805b 0.03
First Episode, Yesc 110 (43.3%) 39 (38.6%) 78 (78.0%) – 41.147b <0.001
Medication, Yesc 209 (80.1%) 75 (72.1%) 59 (58.4%) – 17.739b <0.001

Data are n (%) or mean (SD).


HAMD, Hamilton Depression Scale; HAMA, Hamilton Anxiety Scale; YMRS, Young Rating Scale.
aIs the examination among SZ, BD, MDD, and HC; bis the examination among SZ, BD, and MDD; cis information that was missing for some participants.

The age and sex were not matched among SZ, BD, MDD, and HC. Clinical characteristics were significant differences in SZ, BD, and MDD.

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Zhu et al. Cognition, Symptom and Psychiatric Disorders

TABLE 2 | The five-factor solution for Brief Psychiatric Rating Scale (BPRS). and cognition in individual patients groups can be found in
Dimension Eigenvalue Variance Item Loading
Supplementary Materials (Supplementary Table 1).
(%)a Multiple regression analyses showed that “negative/disorganized
symptoms” predicted scores for HVLT-R (β = −0.402, t = −2.039,
Affective 4.03 22.41 Depression 0.84
P = 0.045), Mazes (β = −0.382, t = −2.084, P = 0.041), CPT-IP (β =
symptoms
Anxiety 0.82 −0.087, t = −3.347, P = 0.001), CR (β = −0.999, t = −4.272, P < 0.001),
Guilt 0.67 CC (β = −0.157, t = −3.865, P < 0.001), TE (β = 1.029, t = 4.39, P <
Tension 0.67 0.001), PE (β = 0.484, t = 2.34, P = 0.02), and NPE (β = 0.488, t =
Somatic Concern 0.60 3.248, P = 0.001) across all patient groups (Table 4).
Psychosis 2.46 13.65 Unusual Thought 0.78
Content
Suspiciousness 0.77
Hostility 0.67 DISCUSSION
Hallucinations 0.66
Negative/ 1.60 8.91 Emotional 0.72
In this study, we identified the factor structure of the BPRS-18 in
disorganized Withdrawal
symptoms SZ, BD, and MDD and examined the relationship between BPRS
Blunted Affect 0.69 EFA factors and cognitive function across the three disorders. We
Motor Retardation 0.62 determined five BPRS EFA factors from EFA: affective symptoms,
Conceptual 0.66 psychosis, negative/disorganized symptoms, activation, and
Disorganization
Disorientation 0.57
noncooperation. Cognitive impairment was observed in all patient
Activation 1.31 7.26 Excitement 0.77 groups, compared to HC, and significant differences in some
Mannerisms and 0.70 cognitive measures were noted between patient groups. “Negative/
Posturing disorganized symptoms” was positively correlated with several
Grandiosity 0.41 cognitive measures across SZ, BD, and MDD and was a significant
Noncooperation 1.11 6.18 Uncooperativeness 0.73
predictor of performance for several cognitive tests (attention, verbal
aIs the cumulative variance, which is 58.41%. learning, problem reasoning and solving, and executive function).
Affective symptoms were composed of Depression, Anxiety, Guilt, Tension, and Somatic
Concern. Psychosis was composed of Unusual Thought Content, Suspiciousness,
Importantly, our findings support prior evidence that
Hostility, and Hallucinations. Negative/Disorganized Symptoms were composed of cognitive dysfunction severity positively correlates with
Emotional Withdrawal, Blunted Affect, Motor Retardation, Conceptual Disorganization, certain dimensions of psychopathology, particularly negative/
and Disorientation. Activation was composed of Excitement, Mannerisms and disorganized symptoms (10).
Posturing, and Grandiosity. Noncooperation included only one Uncooperativeness item.

Cognitive Measures Dimensions of Psychopathology


Compared to the HC group, the SZ, BD, and MDD groups were The National Institute of Mental Health (NIMH) Research
significantly impaired in Maze but did not differ from each Domain Criteria (RDoC) is an emerging research framework
other. Compared to the HC group, the SZ and BD groups were that focuses on the dimensional aspects of neuropsychiatric
significantly impaired in TMT-A, Symbol Coding, Spatial Span, illness based on neural systems rather than a disorder-specific
Letter-Number Span, BVMT-R, and CPT-IP, and the SZ and approach. BPRS appears to be a useful tool for quantifying
MDD groups were significantly impaired in HVLT-R. In Symbol psychopathology across disorders that can be used easily in
Coding, Spatial Span, HVLT-R, and CPT-IP, BD and MDD research and clinical settings. Prior studies have also examined
differed from SZ but did not differ from each other. In TMT-A, the factor structure of the BPRS. Velligon et al. identified a
Letter-Number Span, and BVMT-R, SZ differed from MDD. In four-factor structure (depression/anxiety, psychosis, negative
WCST, comparisons of the HC, SZ, BD, and MDD groups yielded symptoms, and activation) using EFA of the 24-item BPRS across
significant differences in CR, CC, TE, and NPE, and SZ and MDD SZ, BD, and MDD (34). Prior EFA of the BPRS-18 identified four
had significant differences in PE. BD and MDD differed from the factors in depression (citations): EFA factors of apathy, dysphoria,
SZ in CC but did not differ from each other. In CR, TE, and NPE, depression, and psychoticism in 163 unipolar depressive patients
there were differences between SZ and BD. There was no significant (35) and of mood disturbance, positive symptoms/apathy,
difference between BD and MDD in MCCB and WCST (Table 3). bipolarity, and thought distortion/mannerism in 258 patients
with MDD (32). The differences in BPRS-18 factor structure
found herein may relate to sample size, a critical variable in EFA,
Correlations Between Clinical Symptom and sample clinical characteristics. A factor analysis study on
Dimensions and Cognition the BPRS has resulted in a relatively high number of factors -
“Negative/disorganized symptoms” was significantly correlated four or five factors (36). In our study, the sample size was 467,
with neurocognitive function, in most subtests of MCCB and a five-factor solution was determined for the BPRS-18:
(TMT-A, Symbol Coding, Spatial Span, Letter-Number Span, affective symptoms, psychosis, negative/disorganized symptoms,
HVLT-R, Mazes, and CPT-IP) and WCST (CR, CC, TE, and activation, and noncooperation. The five-factor solution presents
NPE) across SZ, BD, and MDD, after false discovery rate patients their own psychopathological characters using the EFA
correction. Correlations between clinical symptom dimensions of BPRS in our study instead of previous works.

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Zhu et al. Cognition, Symptom and Psychiatric Disorders

FIGURE 1 | The Brief Psychiatric Rating Scale (BPRS) total scores and factor scores by diagnosis. Note: *P < 0.05, **P < 0.01, ***P < 0.001. Patient groups differed
on BPRS scores. Bipolar disorder (BD) and major depressive disorder (MDD) groups differed from the schizophrenia (SZ) in “total score,” “affective symptoms,”
“psychosis,” “negative/disorganized symptoms,” and “uncooperativeness” dimensions scores but did not differ from each other. For “activation,” SZ, BD, and MDD
differed from each other.

Comparisons of Cognitive Outcomes Taken together, these findings suggest that cognitive
In our study, cognitive dysfunction appeared most severe in dysfunction may relate more to psychopathology severity rather
SZ, followed by BD and then MDD, compared to HC. For the than the diagnosis itself in SZ, BD, and MDD.
MCCB, the SZ group had a wider range of cognitive deficits
than BD and MDD. Compared to HC, the BD group had
significantly lower scores in six subtests, whereas the MDD Correlations Between Psychopathological
group was only lower in two subtests. Intriguingly, Simonsen Dimensions and Cognition
et al. found that cognitive impairment correlated more with The correlations between clinical symptoms and cognitive
history of psychosis than diagnosis in SZ, schizoaffective functions in SZ and mood disorders are complicated. In our
disorder (SAD), and BD subjects (37). study, “negative/disorganized symptoms” was prominently
Empirical studies and meta-analyses have also shown associated with cognitive dysfunction across SZ, BD, and MDD.
greater degree of cognitive dysfunction in SZ than in BD and However, “negative/disorganized symptoms” was significantly
MDD with psychosis (19, 38–40). Other studies have found but weakly correlated with TMT-A, Category Fluency, and Spatial
similar patterns in SZ and affective psychoses, although Span in MDD after FDR correction. This may be due to the small
cognitive dysfunction severity varied across diagnosis (21, 39, sample size of each patient group. Besides, we still could find the
41). Cognitive function is important in functional outcomes tendency of negative/disorganized symptoms playing potential role
in SZ and affective disorders (42, 43). In addition, cognitive in associating with cognition. Many prior studies have failed to show
deficits often predict similar functional outcomes in affective an association between positive symptoms (e.g., hallucinations and
disorders (44). delusions) and cognitive dysfunction in SZ (45, 46).

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Zhu et al. Cognition, Symptom and Psychiatric Disorders

TABLE 3 | Cognitive performance of SZ, BD, MDD, and HC.

SZ BD MDD HC ANOVA

F P Post hoc

MCCB
N 59 23 24 74
TMT-A 89.22 (72.29) 61.00 (45.18) 46.44 (30.26) 41.47 (24.22) 10.723 <0.001 SZ > MDD, HC; BD > HC
Symbol Coding 38.87 (15.91) 53.87 (14.02) 58.96 (11.98) 59.55 (16.00) 28.946 <0.001 SZ < BD < HC; SZ < MDD
Category Fluency 18.25 (7.04) 20.39 (6.67) 20.50 (5.22) 21.649 (5.96) 2.301 0.079
Spatial Span 11.37 (5.29) 14.61 (6.52) 16.75 (4.50) 17.22 (4.97) 15.862 <0.001 SZ < BD < HC; SZ < MDD
Letter-Number Span 17.25 (5.99) 20.39 (6.79) 22.64 (3.76) 22.85 (4.59) 11.784 <0.001 SZ < MDD, HC; BD < HC
HVLT-R 19.66 (7.01) 26.46 (7.83) 26.20 (4.19) 27.57 (5.00) 21.704 <0.001 SZ < MDD < HC; SZ < BD
BVMT-R 17.15 (8.90) 23.86 (8.63) 24.83 (6.04) 25.97 (7.92) 16.033 <0.001 SZ < BD < HC; SZ < MDD
Mazes 8.95 (6.37) 13.14 (6.82) 12.71 (6.09) 15.18 (6.56) 11.832 <0.001 SZ, BD, MDD < HC
CPT-IP −0.43 (0.95) 0.52 (0.76) 0.74 (0.50) 0.85 (0.54) 37.723 <0.001 SZ < BD < HC; SZ < MDD
MSCEIT 9.02 (2.39) 8.98 (1.70) 8.31 (2.47) 8.88 (1.71) 2.232 0.086
WCST
N 85 89 90 243
CR 19.53 (12.47) 25.12 (12.17) 21.84 (11.25) 28.34 (12.72) 14.444 <0.001 SZ < BD < HC; MDD < HC
CC 1.94 (2.17) 3.01 (2.13) 2.61 (1.94) 3.55 (2.25) 14.144 <0.001 SZ < BD, MDD < HC
TE 28.54 (12.52) 22.54 (12.19) 26.22 (11.23) 19.74 (12.80) 14.353 <0.001 SZ > BD > HC; MDD > HC
PE 11.81 (10.98) 9.25 (8.91) 11.10 (9.57) 7.45 (7.96) 6.194 <0.001 SZ > HC; MDD > HC
NPE 16.73 (8.74) 13.63 (7.00) 15.13 (7.24) 12.16 (7.21) 9.714 <0.001 SZ > BD > HC; MDD > HC

Data are mean (SD).


MCCB, The MATRICS Consensus Cognitive Battery; TMT-A, Trail Making Test–Part A; HVLT-R, Hopkins Verbal Learning Test–Revised; BVMT-R, Brief Visuospatial Memory Test–
Revised; CPT-IP, Continuous Performance Test–Identical Pairs version; MSCEIT, The Mayer–Salovey–Caruso Emotional Intelligence Test; WCST, The Wisconsin Card Sorting Test;
CR, correct responses; CC, categories completed; TE, total errors; PE, perseverative errors; NPE, nonperseverative errors.

TABLE 4 | Correlations between Clinical Symptom Dimensions and Cognition across SZ, BD and MDD.

BPRS Total Affective Psychosis Negative/ Activation Noncooperation


symptoms Disorganized
symptoms

MCCB
TMT-A 0.134(0.199) 0.017(0.867) 0.037(0.724) 0.289(0.005)** 0.032(0.759) −0.095(0.363)
Symbol Coding −0.185(0.075) 0.087(0.407) −0.159(0.127) −0.281(0.006)** −0.193(0.063) −0.059(0.571)
Category Fluency 0.005(0.965) −0.007(0.943) 0.143(0.170) −0.201(0.052) 0.084(0.420) −0.065(0.532)
Spatial Span −0.129(0.217) 0.099(0.345) −0.087(0.407) −0.238(0.021)* −0.187(0.071) −0.086(0.410)
Letter Number Span −0.250(0.015)* −0.068(0.515) −0.153(0.142) −0.289(0.005)** −0.168(0.105) −0.020(0.848)
HVLT-R −0.019(0.854) 0.166(0.109) 0.061(0.562) −0.256(0.013)* −0.145(0.163) −0.032(0.758)
BVMT-R −0.110(0.290) 0.008(0.939) −0.052(0.619) −0.196(0.058) −0.074(0.478) −0.009(0.930)
Mazes −0.153(0.140) 0.017(0.873) −0.095(0.361) −0.234(0.023)* −0.120(0.249) −0.042(0.685)
CPT-IP −0.075(0.473) 0.139(0.181) −0.021(0.841) −0.273(0.008)** −0.117(0.263) −0.073(0.486)
MSCEIT −0.078(0.454) −0.147(0.158) 0.018(0.864) -0.044(0.672) 0.054(0.604) −0.184(0.076)
WCST
CR −0.144(0.024)* −0.003(0.959) −0.101(0.114) −0.282(<0.001)*** −0.049(0.445) −0.076(0.237)
CC −0.148(0.020)* −0.009(0.886) −0.140(0.028)* −0.234(<0.001)*** −0.074(0.247) 0.028(0.666)
TE 0.152(0.017)* 0.007(0.908) 0.113(0.077) 0.287(<0.001)*** 0.040(0.534) 0.079(0.216)
PE 0.125(0.050) 0.018(0.780) 0.122(0.055) 0.186(0.003)** 0.018(0.783) 0.032(0.614)
NPE 0.074(0.249) −0.017(0.786) 0.010(0.874) 0.213(0.001)** 0.054(0.398) 0.108(0.091)

Data are presented as r-value (P-value). Bold indicates significance at p < 0.05, after false discovery rate correction.
*P < 0.05, **p < 0.01, ***p < 0.001.

Instead, previous studies have more consistently found in SZ (49,   50). These inconsistent findings could be
an association between negative symptoms and cognitive attributed to differences in illness duration or stage. Studies
dysfunction in SZ and BD (10), as well as between negative examining the relationship between positive and negative
and disorganized symptoms and cognitive dysfunction (45, symptoms and cognition in MDD are scarce. They have
47, 48). Some studies have also found negative symptoms and found that affective symptoms were weakly linked to
cognitive dysfunction may be separable in SZ and no association cognitive impairments in SZ and schizoaffective disorders
between disorganized symptoms and cognitive dysfunction (50, 51).

Frontiers in Psychiatry | www.frontiersin.org 6 April 2019 | Volume 10 | Article 253


Zhu et al. Cognition, Symptom and Psychiatric Disorders

LIMITATIONS AUTHOR CONTRIBUTIONS


There were several limitations in this study. Most patients were YZ, MC, YT, and FW designed the study. HL, ZY, YW, QZ, SF,
taking psychotropic medications at the time of study participation. XD, JL, YS, YM, XS, JB, SW, and XJ acquired the data. YZ and ST
There were significant differences in sex among the participant analyzed the data. YZ and FYW wrote the article.
groups: There were four times more women than men in the MDD
group. Psychiatric status (active versus remitted illness) was not
accounted for in any of the patient groups. Lastly, there was only ACKNOWLEDGMENTS
a small subset of participants who completed the MCCB. Further
work is needed in a larger sample to confirm results reported here. This work was supported by the National Natural Science
Foundation of China (81571331 to FW and 81571311 and
CONCLUSION 81271499 to YT), the Liaoning Education Foundation (Pandeng
Scholar to FW), the National Key Research and Development
Cognitive dysfunction is present across SZ, BD, and MDD, Program (2016YFC0904300 to FW), the National Key Research
although in varying severity. Across these disorders, negative/ and Development Program (2016YFC1306900 to YT), and the
disorganized symptoms appear most prominently correlated with National High Tech Development Plan (863) (2015AA020513
cognitive dysfunction than other symptom domains, suggesting to FW).
that cognitive dysfunction severity is not necessarily based on We thank all the participants for their cooperation. We are
diagnosis. These findings suggest that negative/disorganized grateful for all the members of Brain Function Research Section
symptoms may be an important target for effective cognitive in the First Affiliated Hospital of China Medical University and
remediation in SZ, BD, and MDD. the support of Shenyang Mental Health Center.

ETHICS STATEMENT SUPPLEMENTARY MATERIALS


This research was approved by the Medical Research Ethics
The Supplementary Material for this article can be found online at:
Committee of the China Medical University and in accordance
https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00253/
with the Declaration of Helsinki. All participants gave written
full#supplementary-material
informed consent, and the adolescent participants’ parents or
legal guardian provided written informed consent after receiving SUPPLEMENTARY TABLE 1 | Correlations between clinical symptom
a detailed description of the study. dimensions and cognition across SZ, BD, and MDD.

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