Download Are Negative Symptoms Associated With

Are Negative Symptoms Associated With
Functioning Deficits in Both Schizophrenia
and Nonschizophrenia Patients?
A 10-Year Longitudinal Analysis
by Ellen S. Herbener and Martin Harrow
creteness and stereotyped thinking (Positive and Negative
Syndrome Scale [PANSS], Kay et al. 1987), as important
negative symptoms. Notably, in a comparison of negative
symptoms scales, Fenton and McGlashan (1992) found
that although negative symptom scales (including the
SANS, the PANSS, and the Pogue-Geile and Harrow
scale [Pogue-Geile and Harrow 1984]) differed somewhat
in how narrowly or broadly negative symptoms were
defined, they showed quite similar and significant correlations with measures of outcome.
Although negative symptoms have received increasing research attention in schizophrenia patients, there has
been less systematic study of their presence in patients
with other diagnoses. Thus, although there is growing evidence that negative symptoms are present in individuals
with various psychiatric diagnoses, it is less clear whether
they are associated with similar cognitive and adaptive
deficits across diagnostic groups. This question is important because it would help us to determine whether it is
appropriate to take a symptom approach to building models for the relationship between pathophysiology and
symptomatology across diagnoses (Andreasen et al. 1995)
in the case of negative symptoms.
It has been suggested that research in schizophrenia
is likely to benefit from a more symptom-focused
approach, given the significant heterogeneity of presentation and pathophysiology (Bentall et al. 1988; Andreasen
and Carpenter 1993; Costello 1993; Buchanan and
Carpenter 1997). Research using a symptom-focused
approach across diagnoses has already proceeded in some
other symptom areas, such as the study of psychosis
(Harrow et al. 1995) and thought disorder (Andreasen and
Powers 1974; Harrow and Quinlan 1977).
There is some support, to date, for the proposal that
negative symptoms may represent a dimension of psy-
Abstract
The current analyses assess the functional correlates of
negative symptoms across diagnoses and across time to
assess the appropriateness of a dimensional approach
to the study of negative symptoms—specifically,
whether negative symptoms should be studied as a single construct across diagnostic groups. Seventy-two
schizophrenia/schizoaffective, 36 other psychotic, and
42 nonpsychotic depressed patients were recruited at
index hospitalization and were followed up 4.5, 7.5,
and 10 years later. At each followup assessment, data
were collected on symptoms and adaptive and cognitive functioning. Analyses indicated that negative
symptoms showed some similar functional associates
in all three diagnostic groups, although results were
strongest for the schizophrenia spectrum patients.
Negative symptoms at the 10-year followup were associated with different patterns of social deficits prior to
index hospitalization in the three diagnostic groups.
The data provide some support for a dimensional
approach to the study of mental illness, with negative
symptoms associated with deficits across diagnosis, but
also provide evidence of some diagnostic differences.
Keywords: Negative symptoms, schizophrenia,
diagnosis, functioning, longitudinal.
Schizophrenia Bulletin, 30(4):813-826, 2004.
Negative symptoms have gained increasing significance
in schizophrenia research over the past 20 years. Research
indicates that negative symptoms appear strongly related
to various functioning deficits and are strong predictors of
long-term poor outcome (McGlashan and Fenton 1992).
Specific definitions of negative symptoms differ; DSM-IV
focuses on affective flattening, alogia, or avolition in its
criteria for schizophrenia, whereas two other widely used
scales for assessment of negative symptoms include various other characteristics, including anhedonia and attention deficits (the Scale for the Assessment of Negative
Symptoms [SANS], Andreasen and Olsen 1982), and con-
Send reprint requests to Dr. E. Herbener, Department of Psychiatry,
University of Illinois College of Medicine, 912 S. Wood St. (M/C 913),
Chicago, IL 60612; e-mail: [email protected].
813
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
E.S. Herbener and M. Harrow
chopathology that is shared across diagnostic groups.
Factor analytic studies comparing symptom structure
across diagnoses have now found similar factors, including negative symptoms, emerging in schizophrenia and
other diagnostic groups (Peralta et al. 1997; Toomey et al.
1998). Furthermore, recent analyses on the phenomenology of negative symptoms across diagnostic groups
(Herbener and Harrow 2001) found that, although the frequency and persistence of negative symptoms were highest in schizophrenia and schizoaffective patients, patients
with other psychotic (OP) disorders were not significantly
different on either measure. In contrast, patients with histories of nonpsychotic depression did show both lower
frequencies of negative symptoms and less persistent negative symptoms than did the schizophrenia/schizoaffective
(SZ/SZAF) group.
One important consideration in studies of negative
symptoms, particularly in mood-disordered patients, is the
need to distinguish between depressive and negative
symptoms. Although there is some overlap in symptoms,
such as psychomotor retardation and loss of interest in
activities, a number of researchers have reported that distinctions among the different types of symptoms can be
reliably accomplished (Bermanzohn and Siris 1992;
Perenyi et al. 1998). Analyses of relationships between
depression and positive and negative symptoms in schizophrenia patients have repeatedly indicated that depression
is associated with psychosis but not with negative symptoms (Norman and Malla 1994; Kohler et al. 1998). Prior
analyses of our sample found nonsignificant correlations
between negative symptoms and major depression in both
schizophrenia and nonschizophrenia patient groups
(Herbener and Harrow 2001). In addition, work with our
sample suggests that individuals with different diagnoses
are not more likely to have different types of negative
symptoms; rather, schizophrenia and schizoaffective subjects tended to show the highest frequency of all types of
negative symptoms measured, OP patients showed an
intermediate frequency, and nonpsychotic depressed
(NPD) patients showed the lowest frequency, and the
diagnostic groups did not statistically differ on severity of
any negative symptom (Herbener and Harrow 2001).
Research on the relationship between negative symptoms and deficits in cognitive functioning in individuals
with schizophrenia has generally found impairments on
measures of executive functioning (Capleton 1996;
Berman et al. 1997; Norman et al. 1997; Voruganti et al.
1997; Baxter and Liddle 1998; Mahurin et al. 1998; Poole
et al. 1999), although a few studies have not found this
relationship (Nuechterlein et al. 1986; Zakzanis 1998).
Negative symptoms have also been associated both
concurrently and predictively with adaptive functioning
deficits in schizophrenia patients, with most studies noting
a particular relationship between negative symptoms and
impairments in social functioning up to 2 years following
symptom ratings (Breier et al. 1991; Ho et al. 1998).
Research on premorbid factors predicting later negative
symptoms in schizophrenia patients has indicated a particular relationship between premorbid social and work
functioning and later negative symptoms (McGlashan and
Fenton 1992). Only a few studies to date have assessed
relationships between negative symptoms and functioning
in nonschizophrenia samples. However, these studies have
found that negative symptoms in bipolar or other nonschizophrenia psychotic patients are associated with cognitive deficits (Johnstone et al. 1992; Dolan et al. 1993) or
adaptive functioning deficits (Pearlson et al. 1984;
Schuldberg et al. 1999) similar to those found in schizophrenia patients.
At this point there is some evidence for the phenomenological similarity of negative symptoms, particularly
across groups with psychotic disorders, as well as similarity between negative symptoms and concurrent functioning deficits across diagnostic groups. The data are generally consistent with the hypothesis that negative
symptoms reflect a similar underlying process across at
least some diagnostic groups, although clearly much additional research is needed before such causal relationships
can be determined. An important step, however, is to
determine whether negative symptoms in nonschizophrenia groups show the same predictive and longitudinal
qualities as negative symptoms in schizophrenia patients.
For example, negative symptoms may be state-related in
nonschizophrenia patients but a trait characteristic in
schizophrenia patients. Or negative symptoms may be
associated with different patterns of impairment in different diagnostic groups. Consistency of relationship
between negative symptoms and adaptive and cognitive
impairment across diagnostic groups will help us to determine whether a domain of psychopathology approach (cf.
Buchanan and Carpenter 1994) is appropriate for the
investigation of negative symptoms.
The current research focused on this issue by using
longitudinal data to assess the relationship between premorbid, concurrent, and predictive correlates of negative
symptoms in SZ/SZAF, OP, and NPD individuals with
major mental illness. Analyses focused on data collected
at the index hospitalization and at 4.5-year, 7.5-year, and
10-year followup assessments. The following questions
are addressed:
1. Are negative symptoms associated with similar concurrent adaptive and cognitive functioning deficits in
all diagnostic groups?
2.
814
Are persistent negative symptoms related to the same
types of deficits across diagnostic groups?
Are Negative Symptoms Associated With Functioning Deficits
3.
Do negative symptoms predict future adaptive and
cognitive functioning deficits? Is this relationship the
same across diagnostic groups?
4.
Are premorbid characteristics predictive of later negative symptoms or persistent symptoms over a 10year period? Is this relationship the same across diagnostic groups?
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
nor the SZ/SZAF group was significantly different from
the OP group in terms of gender distribution.
Acute Phase and Followup Assessments. All 150
patients were assessed prospectively on entering the study
during index hospitalization. Diagnoses were based on at
least one of two structured interviews conducted with the
patients: the Schedule for Affective Disorders and
Schizophrenia (Endicott and Spitzer 1978) or the
Schizophrenia State Inventory, a structured, tape-recorded
interview that has been described in previous reports
(Grinker and Harrow 1987).
During each followup assessment, an established
research protocol was completed, including structured
interviews, performance tests, and observational ratings.
Trained raters who were naive to the diagnoses from
index hospitalization and blind to the results from previous followups completed the interviews and ratings. The
Behavior Rating Scale of the Psychiatric Assessment
Interview (Carpenter et al. 1976) was completed at the
end of each interview.
Method
The current study is part of the Chicago Follow-up Study,
a longitudinal research program designed to investigate
the course of schizophrenia and affective disorders studying prognostic factors, functional and cognitive outcome,
and major symptom dimensions, including thought disorder, psychosis, and negative symptoms (cf. Pogue-Geile
and Harrow 1984, 1985; Grossman et al. 1991; Goldberg
et al. 1995; Harrow et al. 1997).
Patient Sample. The current research included 150
patients studied prospectively at the acute phase of hospitalization and then followed up periodically over the next
10 years. Using Research Diagnostic Criteria, the sample
included 52 schizophrenia and 20 schizoaffective patients,
36 patients who presented at index hospitalization with OP
disorders (21 bipolar psychotic affective disorders, 6
unipolar psychotic depressive disorders, 9 OP disorders),
and 42 patients with nonpsychotic affective disorders.
Diagnosis was completed during the index hospitalization.
Followup interviews studying negative symptoms were
conducted 4.5 years, 7.5 years, and 10 years following initial enrollment in the study. Data about negative symptoms
were available on all 150 patients at the 10-year followup,
on 85 percent of the sample at the 7.5-year followup, and
on 75 percent of the sample at the 4.5-year followup.
Patient recruitment for this study focused on young
patients with recent onset of illness. Seventy-five percent
of the subjects had one or no prior hospitalizations at
index. The mean age of patients at index admission was
22.5 years, and the average ages of patients in the three
diagnostic groups did not differ significantly (F[2,147] =
0.83, p > 0.10). Level of education did vary significantly
between the groups (F[2,146] = 5.43, p < 0.01), with the
SZ/SZAF group showing a lower level of education than
the other two groups (Newman-Keuls post hoc tests, p <
0.05). On average, the SZ/SZAF subjects had completed
high school, whereas subjects in the other two groups had
completed 1 year of college. The SZ/SZAF and NPD
groups differed significantly in gender distribution, with a
higher percentage of females in the NPD group than in the
SZ/SZAF group, a finding consistent with most current
studies of these diagnostic groups. Neither the NPD group
Measures of Negative Symptoms. The negative symptom scale is designed to assess flat affect, poverty of
speech, and psychomotor retardation/poverty, with specific behavioral items quite similar to those used in studies by other research groups (cf. Liddle 1987). These are
aspects of behavior that some but not all researchers have
identified as important to the negative symptom definition
(Crow 1980; Kibel et al. 1993) and include two of the
three negative symptoms used for schizophrenic diagnosis
in DSM-IV (APA 1994). Individual items were combined
into three subscales reflecting poverty of speech, flat
affect, and psychomotor retardation/poverty (see PogueGeile and Harrow 1984, 1985, for details). Ratings were
made by the interviewers at the end of the 3- to 4-hour inperson interview, and scores were based on the subjects'
behavior throughout the full interview period. Intraclass
correlations between raters are 0.96 for the poverty of
speech scale, 0.86 for the flat affect scale, and 0.85 for the
psychomotor retardation/poverty scale. To estimate the
general frequency of negative symptoms, a categorical
index was created. This index required that a subject show
significant pathology on at least one of the three subscales
to be considered as having negative symptoms. Because
psychomotor retardation could potentially reflect depression or side effects of antipsychotic medication, significance on at least one of the other two subscales was
required for the categorical scale. Negative symptoms
were not significantly correlated with gender or education
levels in any of the diagnostic groups.
Assessments of the presence of negative symptoms
were made at each followup. Subjects in all three diagnos-
815
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
E.S. Herbener and M. Harrow
tic groups showed variation in the persistence of negative
symptoms across assessments. We thus also created a
measure of negative symptom persistence based on the
number of followup assessments at which each subject
had negative symptoms. Scores ranged from 0 to 3, and
all diagnostic groups had individuals at both extremes.
Additional information about the persistence of negative
symptoms in each diagnostic group is available in a prior
article focusing on this issue (Herbener and Harrow
2001).
Measures of Medication Use. Medication use was determined by each subject's treating psychiatrist and was not
influenced by involvement in this study. Of the SZ/SZAF
patients, 57 percent were receiving neuroleptic medication at the 10-year followup, 65 percent at the 7.5-year
followup, and 66 percent at the 4.5-year followup. In the
OP group, 34 percent were receiving neuroleptics at the
4.5-year followup, 39 percent at the 7.5-year followup,
and 31 percent at the 10-year followup. In the initially
NPD group, a few patients were later prescribed antipsychotic medications: 7 percent at the 4.5-year assessment,
10 percent at the 7.5-year assessment, and 7 percent at the
10-year assessment. Effects of medication were assessed
using a continuous variable based on chlorpromazine
equivalent units of medications (Dipiro et al. 1997) for
patients on neuroleptics. None of the subjects in the current analyses were using atypical antipsychotic medication. Although the rate of medication prescription in our
sample is lower than that found in clinic-based samples, it
is consistent with rates found in other community-based
samples (McGlashan 1984, 1988).
In previous research with this sample (Herbener and
Harrow 2001), we assessed relationships between the
presence of negative symptoms and antipsychotic medication use in the SZ/SZAF and OP samples. Spearman correlations were nonsignificant for both groups at all three
assessment periods (r = 0.24, r = 0.14, and r - 0.20 for
the SZ/SZAF sample for the 4.5-, 7.5-, and 10-year
assessments, respectively; r = 0.14, r = -0.22, and r =
0.17 for the OP sample for the 4.5-, 7.5-, and 10-year
assessments, respectively). Correlations between negative
symptom severity and neuroleptic dosage were nonsignificant for two of the three assessment periods for the
SZ/SZAF sample, and for all three assessment periods for
the OP sample. Analyses for the current study were completed both with and without medication dosage included
as a covariate; inclusion of medication dosage as a covariate had minimal effect on the negative symptom data and
thus it is not discussed further.
Measures of Adaptive Functioning. Outcome scales
developed by Strauss and Carpenter (1972) were used to
assess rehospitalization, work, and social adjustment at
each followup assessment. The rehospitalization scale
indexed how many months each subject had been hospitalized in the year prior to the followup assessment. The
social function scale assessed the frequency and context of
social interactions, from none or chance encounters with
others to regular planned meetings several times a month.
The work function scale assessed the portion of the prior
year during which the subject had been employed, including part-time or partial-year employment.
Measures of Cognitive Functioning. Four general areas
of cognitive functioning were used in the current analyses: Wechsler Adult Intelligence Scale (WAIS)
Information, which provides a measure of general intellectual ability (Wechsler 1955); WAIS Comprehension,
which measures social comprehension, judgment, and
knowledge; WAIS Digit Symbol, which assesses sustained attention skills and psychomotor coordination; and
Gorham's Proverbs Test (Gorham 1951), which assesses
verbal abstraction abilities. These four tests provided
indexes of both relatively specific abilities in areas related
to negative symptoms—that is, social understanding, psychomotor and attentional skill, and executive functioning—as well as a more general measure of intellectual
ability and educational achievement that would be
expected to be more resistant to change over time (Lezak
1995). Coding of abstraction was based on a system previously used by this research group (Marengo et al. 1980)
with good reliability (r > 0.90). Because of time limitations during followup assessments, some patients were
not able to complete all cognitive tests.
Results
Are negative symptoms associated with similar concurrent adaptive and cognitive functioning deficits in
all diagnostic groups? We assessed the contribution of
diagnosis and the presence of negative symptoms to performance on the adaptive functioning measures at the 4.5,
7.5-, and 10-year followups with univariate analysis of
variance (table 1). At all followup assessments, the presence of negative symptoms was associated with impairment in functioning independent of deficits associated
with diagnosis. Negative symptoms were associated with
impairments in social functioning at all three followup
Measures of Premorbid Functioning. The ZiglerPhillips Social Competence Scale (Zigler and Phillips
1960), which assesses premorbid social functioning, was
completed on subjects at index hospitalization. In addition, trained clinicians rated whether each patient showed
significant schizotypal or schizoid traits based on all
available information at the index hospitalization.
816
Table 1. Relationship between negative symptoms and adaptive functioning at three followups over 10 years for major diagnostic
groups1
n
Schizophrenia/
Schizoaffective
Negative
symptom,
F
Diagnosis by
symptom
interaction,
F
No
negative
symptom
Have
negative
symptom
No
negative
symptom
Have
negative
symptom
No
negative
symptom
Have
negative
symptom
Diagnosis,
F
4.5-yr followup
Rehospitalization
Social function
Work function
3.36
3.03
2.28
3.05
1.95
1.30
3.70
3.10
3.15
3.38
3.13
2.13
3.88
3.29
3.42
3.80
2.60
2.00
3.42*
2.25
4.00*
1.26
3.90*
10.97***
0.12
1.53
0.14
7.5-yr followup
Rehospitalization
Social function
Work function
3.50
3.29
1.56
2.86
2.41
0.64
3.68
3.16
2.88
3.71
2.57
2.86
3.91
3.50
3.47
3.40
2.40
2.00
3.47*
0.04
16.40***
3.15
8.18**
5.91*
1.09
0.20
1.35
10-yr followup
Rehospitalization
Social function
Work function
3.65
2.77
1.67
2.62
2.34
1.41
3.74
3.33
2.26
3.33
3.11
2.33
3.97
3.53
3.55
3.00
2.25
3.00
2.54
2.72
8.09***
15.97***
4.64*
0.46
1.28
0.86
0.20
Followup Year
and Measure
00
Other Psychotic
Nonpsychotic
Depressed
<
•a
o
O
' p < 0.05; " p< 0.01;'" p< 0.001
1
Higher mean scores reflect more favorable functioning in each area.
i
3
S'
to
p
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
E.S. Herbener and M. Harrow
assessments over the 10-year period and were associated
with deficits in work functioning and higher rehospitalization rates at two of the three followup assessments. The
data showed that for the SZ/SZAF and NPD patients, subjects with negative symptoms always performed worse
than those without negative symptoms, whereas in the OP
group, the effects were less consistent (table 1).
Table 2 shows data from analyses of cognitive functioning. Negative symptom presence was associated with
impairments in cognitive functioning in 8 of the 12 analyses. Effects were significant at the 4.5-, 7.5-, and 10-year
followups for assessments of social knowledge and judgment, and of psychomotor functioning. Patients in the
SZ/SZAF and NPD groups who had negative symptoms
consistently performed more poorly than similarly diagnosed patients without negative symptoms in all domains
at all assessments. At the 7.5- and 10-year followups, the
OP patients showed the same pattern as the other two
groups did, with subjects with negative symptoms showing poorer cognitive functioning than those without negative symptoms on all measures.
To assess the role of medication dosage, we also conducted an analysis using medication dosage, in chlorpromazine equivalents, as a covariate. In addition, we used
premorbid social, work, and educational functioning as
covariates for the social, work, and cognitive functioning
measures, respectively, to determine whether premorbid
differences could account for our findings. Inclusion of
these factors diminished some of the effects: as would be
expected, factors such as medication dosage and premorbid abilities also contributed to long-term functioning.
However, patients with negative symptoms were still significantly more likely to show impairments on both psychosocial and cognitive functioning variables over the 10year period.
Are negative symptoms predictive of future adaptive
and cognitive functioning deficits? Is this relationship
the same across diagnostic groups? Correlation coefficients indexing the relationship between negative symptoms at the 4.5-year followup and functioning at the 7.5year followup are presented in table 4. For the full sample,
negative symptoms at the 4.5-year followup were predictive of deficits at the 7.5-year followup on work functioning and on all cognitive measures. When this relationship
was assessed separately by diagnostic group, significant
correlations were found for only the SZ/SZAF group.
Some effect sizes in the OP and NPD groups were at a
medium level (Cohen 1977) but did not reach statistical
significance, probably because of a smaller sample size.
Table 5 reports negative symptom data assessed at the
7.5-year followup predicting psychosocial and cognitive
functioning deficits at the 10-year followup. Negative
symptoms significantly predicted hospitalization and
social functioning difficulties 2.5 years later, as well as
significantly predicting cognitive functioning deficits on
all four measures over the 2.5-year period for the entire
sample. Again, the SZ/SZAF group showed the highest
number of significant relationships, but effect size comparisons indicated no significant differences among the
diagnostic groups. Negative symptoms at the 7.5-year followup significantly predicted rehospitalization for the
SZ/SZAF and NPD groups. The relationship between
negative symptoms at the 7.5-year followup and social
functioning at the 10-year followup was stronger for the
NPD group than the SZ/SZAF group, although neither
reached statistical significance.
On cognitive functioning variables, although the
SZ/SZAF group showed the only statistically significant
relationships, the OP group had a larger effect size on the
Digit Symbol test. Interestingly, all three groups showed a
moderate effect size (i.e., 0.30 or greater; Cohen 1977) for
the relationship between negative symptoms at the 7.5-year
followup and social comprehension at the 10-year followup.
These data indicate that predictive relationships
between negative symptoms at one assessment and psychosocial functioning at a later assessment are inconsistent
over time, even in the SZ/SZAF group, suggesting that this
relationship is not as stable as is sometimes hypothesized.
Furthermore, although relationships between negative
symptoms and functioning variables appear stronger in the
SZ/SZAF group than in other diagnostic groups, comparisons of effect sizes indicate that significant differences are
the exception rather than the rule. These points will be
addressed further in the Discussion.
Are persistent negative symptoms related to the same
types of deficits across diagnostic groups? Table 3
shows correlation coefficients indexing the relationship
between persistence of negative symptoms across the 10year followup period and indexes of psychosocial and
cognitive functioning at the 10-year followup. Persistent
negative symptoms were associated with a higher rate of
rehospitalization for the entire sample. Interestingly, relationships between persistent negative symptoms and psychosocial functioning were generally in the low range for
all diagnostic groups. In contrast, the relationship between
persistent negative symptoms and cognitive functioning
was much higher, with all four measures reaching statistical significance for the entire sample. Furthermore, the
relationship between performance on the comprehension
test and persistent negative symptoms was large and significant for all three diagnostic groups.
Are premorbid characteristics predictive of later negative symptoms or persistent symptoms over a 10-year
818
10.93
10.04
10.59
10.67
11.67
11.82
12.41
10.50
7.5-yr followup
Information
Comprehension
Digit Symbol
Abstraction
1O-yr followup
Information
Comprehension
Digit Symbol
Abstraction
1
9.44
8.58
8.87
6.95
9.30
8.05
8.25
5.00
9.89
7.76
9.06
4.94
12.33
12.67
14.00
12.47
11.70
11.91
11.65
12.32
12.29
11.41
11.56
9.61
No
negative
symptom
Higher mean scores reflect better cognitive functioning in each area.
* p < 0.05; " p< 0.01; *** p < 0.001
11.56
11.25
10.44
10.55
Have
negative
symptom
11.50
9.17
9.50
12.20
10.67
9.50
8.20
9.33
12.50
10.63
9.88
10.14
Have
negative
symptom
Other Psychotic
12.29
13.74
13.42
16.38
12.13
13.21
13.10
14.88
12.13
12.87
13.58
14.43
No
negative
symptom
9.00
9.33
11.00
11.33
11.75
10.50
11.00
13.25
11.60
11.40
12.20
13.20
Have
negative
symptom
Nonpsychotic
Depressed
1.31
0.81
0.87
3.96*
2.22
4.91"
3.96*
6.79**
2.14
5.28**
6.50**
4.06*
Diagnosis,
F
6.20**
15.15***
8.82**
2.68
1.68
8.56**
10.69***
5.52*
0.71
7.16"
4.18*
1.35
Negative
symptom,
F
0.57
0.13
0.20
0.53
0.24
0.08
0.24
0.82
0.64
1.75
0.02
1.37
Diagnosis by
symptom
interaction,
F
VI
•3
o
<
n
3
o
I
=h
o
D
tro
c.
o
5'
3
3
O
s-
<
g.
&n
Ass
4.5-yr followup
Information
Comprehension
Digit Symbol
Abstraction
Followup Year
and Measure
No
negative
symptom
Schizophrenia/
Schizoaffective
Table 2. Relationship between negative symptoms and cognitive functioning at three followups over 10 years for major diagnostic
groups
egati
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
E.S. Herbener and M. Harrow
Table 3. Persistence of negative symptoms and functioning at 10-year foiiowup
Functioning at
10-yr foiiowup
Full sample,
r
Schizophrenia/
schizoaffective, r
Adaptive functioning
Rehospitalization
Social function
Work function
-0.23*
-0.07
-0.14
-0.23
-0.06
-0.13
Cognitive functioning
Information
Comprehension
Digit Symbol
Abstraction
-0.41***
-0.54***
-0.31**
-0.30**
-0.42**
-0.53***
-0.36*
-0.42**
Other psychotic,
r
Non psychotic
depressed,r
0.03
0.02
0.06
0.05
0.22
0.11
-0.31
-0.55*
-0.21
0.09
-0.39*
-0.49*
-0.10
-0.07
* p< 0.05; " p< 0.01; *** p< 0.001
Table 4. Correlations between the presence of negative symptoms at 4.5-year foiiowup and functioning
at 7.5-year foiiowup
Negative Symptoms at 4.5-yr Foiiowup
Functioning at
7.5-yr foiiowup
Full sample,
r
Schizophrenia/
schizoaffective, r
Other psychotic,
r
Nonpsychotic
depressed,r
Adaptive functioning
Rehospitalization
Social function
Work function
-0.11
-0.14
-0.31***
-0.12
-0.08
-0.31*
0.24
-0.17
-0.14
-0.14
-0.20
-0.30
Cognitive functioning
Information
Comprehension
Digit Symbol
Abstraction
-0.30**
-0.38***
-0.27**
-0.34**
-0.42**
-0.45**
-0.25
-0.46**
-0.21
-0.20
-0.19
-0.30
0.12
-0.36
-0.16
0.02
r
p < 0.05; ** p < 0.01; *** p < 0.001
Table 5. Correlations between the presence of negative symptoms at 7.5-year foiiowup and functioning at 10-year foiiowup
Negative Symptoms at 7.5-yr Foiiowup
Functioning at
10-yr foiiowup
Full sample,
r
Schizophrenia/
schizoaffective, r
Other psychotic,
r
Nonpsychotic
depressed, r
Adaptive functioning
Rehospitalization
Social function
Work function
-0.41***
-0.22"
-0.16
-0.41"
-0.25
-0.16
-0.12
0.14
0.21
-O.40**
-0.31
-0.09
Cognitive functioning
Information
Comprehension
Digit Symbol
Abstraction
-0.24*
-0.43***
-0.34***
-0.26**
-0.23
-0.42**
-0.28
-0.30*
-0.15
-0.38
-0.40
0.03
-0.25
-0.34
-0.21
-0.08
* p< 0.05; " p< 0.01; *** p< 0.001
820
Are Negative Symptoms Associated With Functioning Deficits
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
period? Is this relationship the same across diagnostic
groups? Correlations between measures of premorbid
functioning and negative symptom presence at the 10-year
followup assessments are shown in table 6. Both premorbid
social competence levels and premorbid schizoid traits
were significantly predictive of the presence of negative
symptoms for the full sample 10 years later (p < 0.05), and
premorbid schizotypal traits showed a trend in the same
direction over the 10-year period (p < 0.10). Premorbid
social competence significantly predicted negative symptoms in the SZ/SZAF group. Premorbid schizoid characteristics showed a trend-level relationship with negative
symptoms at the 10-year followup in the SZ/SZAF group,
with the same effect size in the NPD group. Premorbid
schizotypal traits showed trend-level relationships with
negative symptoms for the SZ/SZAF and OP groups but
not for the NPD group. Overall, the data indicate that some
aspects of premorbid social functioning measured at index
hospitalization were significant predictors of negative
symptoms measured 10 years later for the full sample of
patients and for the SZ/SZAF sample. Although none of the
relationships between premorbid characteristics and negative symptoms reached statistical significance for the nonschizophrenia groups, effect sizes were quite similar for
several predictive relationships. Specifically, effect sizes
were identical for the relationship between premorbid
schizoid traits and later negative symptoms in the SZ/SZAF
and NPD groups, and premorbid schizotypal traits were
even more strongly predictive of negative symptoms in the
OP group than in the SZ/SZAF group.
toms predict some later deficits in adaptive and cognitive
functioning in all three diagnostic groups, with the effect
consistently being strongest in the SZ/SZAF group and in
the cognitive domain; (3) persistent negative symptoms
are strongly associated with cognitive impairment, with
this effect holding true for all three diagnostic groups; and
(4) some premorbid characteristics are predictive of negative symptoms assessed 10 years later in all diagnostic
groups. In all analyses, relationships between negative
symptoms and functioning were strongest for the
SZ/SZAF group. However, statistical comparisons of
effect sizes typically found no or few significant differences among diagnostic groups. The present research fits
in with previous research of ours and of other investigators indicating that negative symptoms are not exclusive
to schizophrenia, or of importance in only schizophrenia.
Since the 1980s there has been a resurgence of interest in the negative syndrome in schizophrenia patients,
and substantial research has indicated that negative symptoms reflect an important aspect of schizophrenic pathology. It has been less clear whether negative symptoms
should be considered a dimension of pathology that
occurs across diagnostic groups (but is most common in
schizophrenia patients) or whether negative symptoms
reflect different processes in different diagnostic groups.
The relationship between cognitive functioning measures
and negative symptoms is particularly interesting because
it would support a hypothesis that deficits in optimal brain
functioning may be contributing to the presentation of
both symptoms and cognitive functioning impairment and
that this mechanism could be shared across diagnostic
groups.
However, the current research also suggests additional questions and differences as well as similarities in
the import of negative symptoms across diagnoses.
Negative symptoms do appear to be associated with concurrent adaptive and cognitive functioning deficits across
diagnostic groups. However, the predictive ability of negative symptoms is not consistent in SZ/SZAF or in other
diagnostic groups. A number of issues are raised by the
Discussion
Our analyses assessed the relationship between negative
symptoms and functioning both longitudinally over a 10year period and across diagnoses. Our results indicate that
(1) negative symptoms are associated with concurrent
deficits in both adaptive and cognitive functioning in all
three diagnostic groups, with this relationship holding
across multiple followup assessments; (2) negative symp-
Table 6. Correlations between premorbid characteristics and negative symptoms at 10-year followup
Premorbid functioning
measure
Full sample,
r
Schizophrenia/
schizoaffective, r
Other psychotic,
r
Nonpsychotic
depressed, r
Zigler-Phillips
Social Competence
0.28***
0.26*
0.01
0.22
Premorbid schizoid
0.21*
0.22
0.08
0.22
Premorbid schizotypal
0.16
0.22
0.28
-0.10
* p< 0.05; " p< 0.01; ***p< 0.001
821
Schizophrenia Bulletin, Vol. 30, No. 4, 2004
E.S. Herbener and M. Harrow
differences in our concurrent and predictive data: (1) concurrent relationships tend to be stronger than predictive
relationships, which suggests that even the transient presence of negative symptoms co-occurs with impairments in
adaptive and cognitive functioning; and (2) negative
symptoms are inconsistently predictive of particular psychosocial deficits, so although negative symptoms appear
to be related to some decrement in functioning, we have
not yet identified what incapacity they are most strongly
linked with. Because most studies look at concurrent relationships or focus on a single predictive period, there is
little opportunity to evaluate the consistency of prediction
across time. This makes longitudinal analyses even more
imperative as a way to distinguish between relationships
that appear by chance and relationships that show consistency over time.
Negative symptoms are sometimes assumed to be
persistent over time. Although our data suggest that
negative symptoms are persistent over prolonged periods of time for some subjects, this finding appears to
be the exception rather than the rule. In previous analyses with this sample (Herbener and Harrow 2001), we
found that 19 percent of our SZ/SZAF sample presented with negative symptoms across all three assessment periods, whereas 41 percent showed symptoms at
one or two assessments and 40 percent did not show
negative symptoms at any of the three assessment periods. The current analyses thus addressed the issue of
the relationship between negative symptoms and functioning in two ways: first by looking at relationships
with the presence of negative symptoms at individual
assessment periods and related functioning, and second, by looking at measures of persistent symptoms
and functioning correlates.
Our analyses of persistent symptoms indicate that
they are related to some similar cognitive deficits in all
three diagnostic groups. The large and significant correlations between persistent symptoms and performance on
the Comprehension subtest are particularly notable.
Furthermore, negative symptoms were strongly and consistently associated with concurrent impairments in both
social comprehension and social functioning at all three
followup assessments. The strength and consistency of the
relationship between negative symptoms, impairment on
measures of social understanding, and low rates of social
interaction support other recent research that has noted the
importance of social cognition in rehabilitation for schizophrenia patients (Hogarty and Flesher 1999). Our data on
premorbid characteristics and later negative symptoms
also generally support the idea that negative symptoms
are associated with some social impairments early in
development. Interestingly, both premorbid schizoid and
premorbid schizotypal traits showed trend-level predictive
relationships with later negative symptoms, suggesting
that both cognitive characteristics, such as the odd beliefs
typically associated with schizotypy, and withdrawn
behavior (more strongly associated with schizoid behavior), may indicate a vulnerability to later negative symptoms. It is also possible that negative symptoms are
related to somewhat different vulnerability factors in different diagnostic groups, with individuals in the SZ/SZAF
group showing a higher incidence of both types of vulnerability factors. These findings are consistent with other
recent research suggesting some significant overlap in
vulnerability factors to SZ/SZAF and OP disorders
(Gershon 2000).
Persistent negative symptoms in the SZ/SZAF group
were significantly related to all aspects of cognitive functioning measured, whereas persistent symptoms were
related to only a few aspects of cognitive functioning in
other groups. One interpretation of this finding is that negative symptoms reflect a pathological mechanism that can
occur across diagnostic groups but that a second factor
may act to increase the severity and degree of impairment
associated with negative symptoms in the SZ/SZAF
group.
Research on the relationship between negative symptoms and adaptive and cognitive functioning impairments
has often been limited to assessments of individuals with
schizophrenia. The current research assessed whether
impairments that have been associated with negative
symptoms in schizophrenia patients also hold true for
other diagnostic groups and whether effects are consistent
across time. Our results did show a significant relationship between negative symptoms and deficits in psychosocial and cognitive functioning in all three diagnostic
groups, although the relationship is stronger in SZ/SZAF
subjects than in other diagnostic groups. It is interesting to
note that in studies of psychotic symptoms, comparisons
across diagnostic groups have also found that schizophrenia patients suffer more intense or persistent symptoms
than do other diagnostic groups (Harrow et al. 1995).
Overall, our results support a dimensional approach to
studying psychopathology and raise additional questions
about mechanisms that may or may not be shared across
diagnostic groups.
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The Authors
Acknowledgments
Ellen S. Herbener, Ph.D., is Assistant Professor, and
Martin Harrow, Ph.D., is Professor and Head of
Psychology, Department of Psychiatry, University of
Illinois College of Medicine, Chicago, IL.
This work was supported in part by a Young Investigator
Award from the National Alliance for Research in
Schizophrenia and Depression to the first author, and grant
825