Escala
Escala
Escala
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).
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
The age and sex were not matched among SZ, BD, MDD, and HC. Clinical characteristics were significant differences in SZ, BD, and MDD.
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.
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).
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
TABLE 4 | Correlations between Clinical Symptom Dimensions and Cognition across SZ, BD and MDD.
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).
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