Psychiatry Research 198 (2012) 34–38

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Psychiatry Research
journal homepage: www.elsevier.com/locate/psychres

The relationships of positive and negative symptoms with neuropsychological

functioning and their ability to predict verbal memory in psychotic major depression
Andrea M. Che a, Rowena G. Gomez a, b,⁎, Jennifer Keller b, Anna Lembke b, Lakshika Tennakoon b,
Gregory H. Cohen c, Alan F. Schatzberg b
a
Pacific Graduate School of Psychology, Palo Alto University, 1791 Arastradero Road, Palo Alto, CA 94304, United States
b
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305–5723, United States
c
San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, United States

a r t i c l e i n f o a b s t r a c t

Article history: Neuropsychological functioning, in relation to positive and negative symptoms in psychotic major depression
Received 23 June 2011 (PMD), has not been as thoroughly studied as it has been in schizophrenia. Thus, the current study investi-
Received in revised form 30 November 2011 gated the associations between positive and negative symptoms with cognitive functioning, with an empha-
Accepted 1 December 2011
sis on verbal memory in PMD. Attention, working memory, and the executive functioning domains were
analyzed among 49 PMD participants. Positive symptoms did not correlate significantly with any measures
Keywords:
Mood disorders
of verbal memory but did correlate with one measure of attention, working memory, and executive function-
Cognition ing. Negative symptoms correlated significantly with two California Verbal Learning Test-II (CVLT-II) mea-
Neuropsychology sures of verbal memory and three measures of executive function. Hierarchical regressions were conducted
to determine if negative symptoms could predict verbal memory performance after controlling for depres-
sion. Of the two verbal memory measures, negative symptoms significantly explained additional variance
for CVLT Recognition, but not for CVLT Trials 1–5 total score. Our results provide some evidence that, consis-
tent with the schizophrenia literature, negative symptoms contributed more to verbal memory deficits in
PMD than positive symptoms, regardless of depression severity.
© 2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction The estimated prevalence of PMD is 0.4% (Ohayon and Schatzberg,

2002). It typically occurs in people who experience severe depression,
Neuropsychological functioning as it relates to types of psychotic though patients with mild to moderate depression also may report psy-
symptoms in psychotic major depression has not been as thoroughly chotic symptoms (Ohayon and Schatzberg, 2002). About 15% of major
studied as it has in schizophrenia. By definition, psychotic major de- depressed patients have psychotic features, which can occur in any
pression (PMD) involves the presence of either delusions or halluci- age group (Schatzberg et al., 1995). Studies have mainly focused on
nations only during major depressive episodes. This restriction the unipolar subtype of psychotic depression since it is more prevalent
distinguishes it from schizoaffective disorder. Psychotic symptoms than the bipolar subtype (Schatzberg et al., 1985). According to Ohayon
in depression can occur in any age group, starting from adolescence and Schatzberg (2002), 2.4% of individuals surveyed across five Europe-
(Schatzberg et al., 1995). The contents of the delusions or hallucina- an countries met criteria for unipolar major depression, of whom about
tions (usually auditory) are generally mood-congruent psychotic fea- 19% had major depression with psychotic features.
tures since they are very commonly consistent with the individual's In general, research studies indicate neuropsychological impair-
depressive themes (American Psychiatric Association, 2000). Delu- ment for PMD patients in the cognitive domains of attention, proces-
sional themes typically include guilt and nihilism (Schatzberg et al., sing speed, working memory, language, verbal memory, visual
1995). Though less common, the psychotic features of PMD patients memory, and executive function (Lesser et al., 1991; Jeste et al.,
may be mood-incongruent, for example, delusions of persecution 1996; Basso and Bornstein, 1999; Fleming et al., 2004; Gomez et al.,
(without depressive themes that the individual deserves to be perse- 2006; Politis et al., 2004; Schatzberg et al., 2000; Simpson et al.,
cuted), thought insertion, thought broadcasting, or thought control 1999; Wang et al., 2008). Compared to healthy participants and
(American Psychiatric Association, 2000). those with nonpsychotic major depression (NPMD), PMD patients
performed most poorly on the cognitive measures (Basso and
Bornstein, 1999; Jeste et al., 1996; Politis et al., 2004). In addition, re-
⁎ Corresponding author at: Pacific Graduate School of Psychology, Palo Alto University,
search has indicated that the cognitive profile of PMD patients is sim-
1791 Arastradero Road, Palo Alto, CA 94304, United States. Tel.: +1 650 433 3823. ilar to that of schizophrenia, but the deficits appear to be milder (Hill
E-mail address: rgomez@paloaltou.edu (R.G. Gomez). et al., 2004).

0165-1781/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.psychres.2011.12.001
 A.M. Che et al. / Psychiatry Research 198 (2012) 34–38 35

In contrast to schizophrenia, there are very few studies to date et al., 2006). Inclusion/exclusion criteria were also based on clinical laboratory tests
such as for pregnancy (for women) and recent substance abuse. The final diagnosis
that investigate whether specific types of psychotic symptoms, such
of PMD was determined by the research psychiatrist, after evaluation of SCID and
as positive and negative symptoms, relate to cognitive functioning BPRS data. Individuals who were pregnant or lactating, had serious medical illnesses,
in PMD. In the schizophrenia literature, positive symptoms involve had history of neurological disorders or head injury, had abnormal clinical laboratory
an excess or distortion of the patient's normal functioning that in- tests, were taking system steroids, or were not within the age range 18–75 were ex-
cludes hallucinations, delusions, disorganized speech or positive cluded from the study. Further exclusions included history of reading or learning dis-
abilities, obsessive compulsive disorder, and history of substance abuse within the
thought disorder. Negative symptoms involve the absence or signifi- last 6 months. The demographics of the PMD patients are depicted in Table 1. The
cant decline of normal functioning such as apathy, avolition, and pov- mean age of the patients is 37.71, S.D. = 12.23, and their mean level of education is
erty of speech. Several studies suggest that positive and negative 15.04 years, S.D. = 2.71.
symptoms are associated with different patterns of performance def-
icits on cognitive tests (e.g., Addington et al., 1991; Hill et al., 2004; 2.2. Measures
Kuperberg and Heckers, 2000). Addington and Addington (2002)
2.2.1. Psychiatric rating scales
found that negative, but not positive, symptoms correlated with cog- The positive, negative, and affective symptoms of the PMD patients were measured
nitive functioning in schizophrenia. Hill et al. (2004) reported no sig- using the Brief Psychiatric Rating Scale (BPRS). The positive symptoms in the current
nificant relationships between positive symptoms and cognitive study included hallucinatory behavior, conceptual disorganization, and unusual
measures in schizophrenic patients, but they did find that negative thought content. The negative symptoms included blunted affect, psychomotor retar-
dation, and emotional withdrawal. These positive and negative scales were derived
symptoms correlated with executive functioning tasks in their sam- from items outlined by Faustman et al. (1988) and Thiemann et al. (1987). The pa-
ple. Negative symptoms appear to correlate more with verbal memo- tients' severity of depression was measured by the 24-item Hamilton Depression Rat-
ry deficits than positive symptoms in schizophrenia (Addington and ing Scale (Ham-D).
Addington, 2002; Aleman et al., 1999; Hughes et al., 2003).
Very few studies have compared PMD and schizophrenia directly 2.2.2. Cognitive measures
Attention, working memory, verbal memory, and executive function were the do-
on both psychotic symptoms and neuropsychological functioning.
mains that were analyzed, with an emphasis on PMD patients' verbal memory perfor-
Hill et al. (2004) found similarities between the cognitive profiles of mance. To assess for the PMD patients' attention, the Wechsler Adult Intelligence
schizophrenia and psychotic major depression, although patients Scale-III (WAIS-III) Digit Span Forward (DSF) subtest, Trail Making Test, Part A, and
with schizophrenia had greater deficits in executive functioning and Wechsler Memory Scale-III (WMS-III) Spatial Span Forward were administered to
attention. Clinically, they also found that positive, but not negative the participants. Working memory was measured by the WAIS-III Digit Span Backward
(DSB), the Letter Number Sequencing (LNS), and the WMS-III Spatial Span Backward
symptoms were more severe in the schizophrenia group as compared subtest. Verbal memory and learning was measured by the California Verbal Learning
to the PMD group. Notably, significant relationships were not ob- Test-II (CVLT-II). Furthermore, executive functioning was measured by the Trail Mak-
served between positive symptoms and neuropsychological variables ing Test Part B, Stroop Test, a phonemic fluency test (Controlled Oral Word Associa-
in either the schizophrenia or PMD group. Notably, they did not com- tion—COWA), and a semantic fluency test (animal fluency test). Raw scores of these
measures were used in the analyses.
ment on the relationship of negative symptoms to cognitive function-
ing in the PMD group. One limitation of that study was the relatively
2.3. Procedures of the original study
small sample size of the PMD group (n = 20) which may hinder the
ability to find such relationships. This article attempts to clarify this Data were collected at the Depression Research Clinic at Stanford University School of
issue using a larger PMD sample. Medicine. Individuals were first screened over the phone, and those with mood symptoms
were scheduled for an eligibility interview, which consisted of the Structured Clinical In-
In sum, many previous investigations have demonstrated the
terview for DSM-IV (SCID) and mood ratings (Ham-D and BPRS) to ensure eligibility for
presence of cognitive deficits in PMD based on neuropsychological the studies. Afterwards they were administered a neuropsychological battery, mood rat-
test performance, but very few studies have investigated the relation- ing scales, self-report questionnaires, overnight blood draws at the Stanford University
ships between positive and negative symptoms of PMD and cognitive Hospital General Clinical Research Center (GCRC) to assess cortisol levels, and magnetic
performance. Therefore, the current study investigated the associa- resonance imaging scans for the baseline study.

tions between positive and negative symptoms with cognitive func-

2.4. Statistical analyses
tioning, with a particular focus on verbal memory. We predicted
that as both positive and negative psychotic symptoms increased, All statistical analyses were carried out with the Statistical Package for the Social
cognitive performance would worsen. We also examined the predic- Sciences (SPSS) version 19.0 for Windows (Somers, NY, IBM Cooperation 2010). Pear-
tive roles of positive and negative symptoms on cognition after con- son correlation coefficients were calculated to assess the relationship between positive
and negative symptoms with the raw scores of the cognitive variables, since the data
trolling for depression severity to obtain a clearer understanding of
were normally distributed. Hierarchical regressions were conducted to determine the
verbal memory deficits in PMD patients and to determine if the pat- ability of negative symptoms to predict verbal memory after controlling for depression
terns of relationship between positive and negative symptoms to severity. Notably, age and education as potential demographic covariates were not sig-
memory functions were similar to those seen in patients with nificantly correlated with any of the dependent variables.
schizophrenia.
3. Results
2. Methods

Table 2 reports the descriptive statistics for all variables of inter-

The data for this study were collected between 2002 and 2011 in studies on the func-
tion of the hypothalamus–pituitary–adrenal (HPA) axis in depression at the Stanford Uni- est. Because a negative relationship was predicted between severity
versity Medical Center. For further details about the broader HPA study, please see Flores of psychotic symptoms and cognitive functioning, one-tailed Pearson
et al. (2006), Keller et al. (2006), and Gomez et al. (2006). Only the baseline (pretreat- correlations were conducted between the positive and negative
ment) neuropsychological and psychiatric assessments were used for this study.

2.1. Participants Table 1

PMD participant characteristics (N = 49).
Forty-nine (21 males and 28 female) PMD participants were recruited by inpatient
and outpatient facilities at Stanford or were self-referred by online and community ad- Variable Frequency Mean Standard deviation Range
vertisements (Flores et al., 2006). Inclusion criteria included an eligibility screening of
Age 37.71 12.23 18–66
the Structured Clinical Interview for the DSM-IV (SCID; First et al., 1997), a score of at
Education level (years) 15.04 2.71 9–23
least 21 or higher on the 21-item Hamilton Depression Rating Scale (Hamilton, 1960),
Gender
and at least a score of 5 on the Brief Psychiatric Rating Scale Positive Symptom Subscale
Male 21
(BPRS PSS; Overall and Gorham, 1962). The BPRS PSS included the following four
Female 28
items: hallucinations, delusions, thought disorganization, and suspiciousness (Flores
36 A.M. Che et al. / Psychiatry Research 198 (2012) 34–38

Table 2 (r = 0.24, p = 0.05), Stroop color raw (r = −0.36, p = 0.01), and

Descriptives of the positive and negative symptoms of the BPRS and cognitive COWA FAS raw (r = − 0.38, p = 0.01).
performance.
Table 4 portrays the hierarchical regression analyses of the two
Cognitive performance Mean SD Range measures of the verbal memory variable (CVLT-II) as the dependent
Hamilton Depression total 37.13 6.95 21.00–50.00 variable, depression severity as the covariate entered at Step1, and
Positive symptoms 2.86 0.95 1.00–5.00 negative symptoms as the predictor entered at Step 2. After control-
Negative symptoms 2.89 1.18 1.00–6.00 ling for depression in these multiple regressions, the negative symp-
Attention
toms accounted for an additional 7% of the variance in CVLT-II Trials
Digit Span Forward 10.49 2.96 4.00–16.00
Trail Making Test (Part A) 33.64 15.16 12.00–77.00 1–5 raw total score, but that was not significant. However, negative
Spatial Span Forward 8.50 1.57 4.00–13.00 symptoms significantly account for an additional 8% variance for the
Working memory CVLT-II Recognition Raw Hits measure.
Digit Span Backward 6.89 2.41 3.00–13.00
Letter-Number Sequencing 9.57 2.81 2.00–15.00
Spatial Span Backwards 7.75 1.57 5.00–10.00 4. Discussion
Verbal memory
CVLT-II
Trials1–5 raw total 43.38 13.23 8.00–75.00
The purpose of this study was to examine the relations between
Recognition raw hit 13.74 3.12 0.00–16.00 positive and negative symptoms with verbal memory performance
Executive function of patients with psychotic major depression (PMD). Research has in-
Trail Making Test (Part B) 79.44 34.45 33.00–189.00 dicated that the neuropsychological profile of PMD is similar to that of
Stroop Test
schizophrenia (Hill et al., 2004). Because both positive and negative
Word raw 88.72 23.12 9.00–140.00
Color raw 62.89 14.30 20.00–93.00 symptoms have been found to be related to deficits in cognitive per-
Color-word raw 36.26 10.38 16.00–60.00 formance among schizophrenic individuals (Addington et al., 1991),
COWA we hypothesized that greater severity of these symptoms would
FAS raw 37.38 11.66 12.00–73.00 also be related to poorer cognitive performance in PMD.
Animals raw 18.14 6.75 0–50.00
Correlations indicated that one measure each of attention, work-
ing memory, and executive function was correlated with the positive
symptoms of BPRS. In contrast, the CVLT-II verbal memory measures
symptoms of the BPRS and variables in each cognitive domain (atten-
and three measures of executive function correlated with the nega-
tion, working memory, verbal memory, and executive function). The
tive symptoms of the BPRS. These results suggest that the cognitive
relationships between the symptoms and variables in each cognitive
measures were more closely associated with negative symptoms
domain are presented in Table 3. Results indicate that positive symp-
rather than positive symptoms. This finding is consistent with the
toms were correlated with one attention measure, Trail Making Test,
schizophrenia literature (Carter et al., 1996; Berman et al., 1997;
Part A, (r = 0.27, p = 0.04), one working memory measure, Letter-
Bilder et al., 2000; McGrath et al., 2001; Silver et al., 2003;
Number Sequencing (r = −0.34, p = 0.01) and one executive func-
Greenwood et al., 2005; Morrens et al., 2007; Guillem et al., 2008;
tion measure, Trail Making Test, Part B (r = 0.36, p = 0.01). Positive
Rodriquez-Sanchez et al., 2008). Findings of the current study are
symptoms were not significantly correlated with any measures of
also consistent with previous studies that have found that negative
verbal memory.
symptoms are significantly correlated with verbal memory deficits
Negative symptoms were significantly correlated with two mea-
in schizophrenic patients (Aleman et al., 1999; Addington and
sures of verbal memory from the CVLT: Trials1–5 raw total (r =
Addington, 2002; Vaz and Heinrichs, 2002; Hughes et al., 2003). In
−0.24, p = 0.04) and Recognition Raw Hit (r = −0.29, p = 0.03).
fact, several studies have found that negative symptoms in schizo-
There were also significant correlations between negative symptoms
phrenia are highly associated with these verbal memory measures
and three measures of executive function: Trail Making Test, Part B
(Aleman et al., 1999; Addington and Addington, 2002; Vaz and
Heinrichs, 2002; Hughes et al., 2003).
Table 3 In our study, of the two verbal memory measures used in the hier-
One-tailed Pearson correlations of the positive and negative symptoms of the BPRS
archical regressions, negative symptoms significantly predicted CVLT
with cognitive performance.
recognition after controlling for depression severity in this PMD sam-
Cognitive performance Positive Negative ple, but were only marginally significant for the CVLT Trials 1–5 total.
Attention This is consistent with what has been found in studies on schizophre-
Digit Span Forward − 0.22 − 0.10 nia (Aleman et al., 1999; Addington and Addington, 2002; Hughes et
Trail Making Test (Part A) 0.27⁎ 0.16
Spatial Span Forward − 0.07 − 0.04
Working memory Table 4
Digit Span Backward − 0.05 − 0.10 Hierarchical regressions of depression and negative symptoms predicting verbal
Letter-Number Sequencing − 0.34⁎⁎ − 0.24 memory.
Spatial Span Backwards − 0.07 − 0.04
Variable B SEB β Increment in R2
Verbal memory
CVLT-II Trials 1–5 raw total
Trails1-5 raw total − 0.03 − 0.24⁎ Step 1 0.04
Recognition Raw Hit − 0.05 − 0.29⁎ Depression 0.36 0.27 0.19
Executive function Step 2 0.07†
Trail Making Test (Part B) 0.36⁎⁎ 0.24⁎ Depression 0.39 0.27 0.21
Stroop Test Negative symptoms − 2.80† 1.54 0.26†
Word raw 0.10 − 0.17 Recognition
Color raw − 0.06 − 0.36⁎⁎ Step 1 0.00
Color-word raw − 0.19 − 0.19 Depression − 0.01 0.07 − 0.03
COWA Step 2 0.08⁎
FAS raw 0.21 − 0.38⁎⁎ Depression − 0.00 0.06 − 0.01
Animals raw − 0.08 − 0.03 Negative symptoms − 0.74⁎ 0.37 − 0.29⁎
⁎ p b 0.05. †
p b 0.10.
⁎⁎ p b 0.01. ⁎ p b 0.05.
 A.M. Che et al. / Psychiatry Research 198 (2012) 34–38 37

al., 2003). Therefore, the current study provides some evidence that research for PMD patients since they have been excluded from de-
the association between negative symptoms and verbal memory def- pression psychotherapy trials. This study suggests that mental health
icits is a common characteristic for both PMD and schizophrenia, re- researchers who do want to examine efficacy of psychotherapy in
gardless of depressed mood. This finding, however, is inconsistent PMDs should be aware that a PMD patient's verbal memory deficits
with the Hill et al. (2004) study, which did not report significant rela- and limitations may be related to negative symptoms and not just re-
tionships between negative symptoms and cognitive functioning in lated to depression. Thus, even if depression improves with therapy,
PMD. One possible explanation is that the Hill et al. (2004) study it may not necessarily mean that cognitive functioning, specifically
may have been underpowered due to a small PMD sample size. An- verbal memory, will also improve in PMD patients.
other possible explanation is that our sample had PMD patients
who were allowed to stay on medication, whereas Hill et al.'s sample
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