Negative Symptoms and Cognitive Deficits: What Is the Nature of
Philip D. Harvey1–3, Danny Koren4,5, Abraham
Reichenberg2, and Christopher R. Bowie2,3
2Department of Psychiatry, Mt. Sinai School of Medicine,
New York, NY;3Department of Veterans Affairs, VISN-3 Mental
Illness Research, Education, and Clinical Center;4Department of
Psychology, University of Haifa, Haifa, Israel;5Department of
Psychiatry, Harvard Medical School, Boston, MA
Negative symptoms and cognitive deficits in schizophrenia
share many features and are correlated in their severity on
a cross-sectional basis. The question arises as to the nature
of this relationship: are these symptoms the same, caused
by the same factor (or factors); or is the nature of their re-
lationship determined by other factors, such as definitional
issues and common correlates? In this article we provide
a conceptual overview for addressing this question and
provide a selective review of the literature on the cross-
sectional and longitudinal relationships between these
two features of the illness. We describe 4 different models
of the ‘‘true’’ relationship between these variables. Some
data suggest that the relationship between these variables
is determined by the definition of negative symptoms
employed and that, in general, the correlation is moderate
to be addressed with later research, that correlations be-
tween negative and cognitive symptoms and everyday func-
tional outcomes may influence the observed correlations
between these variables. Thus, we conclude that negative
and cognitive symptoms may be separable, if not concep-
tually independent, domains of the illness and that it might
be possible to develop treatments that target negative
symptoms and cognitive deficits independently.
Key words: path analysis/longitudinal studies/
Negative and cognitive symptoms in schizophrenia share
many characteristics, at least superficially. Their preva-
lence, course, prognostic importance, and correlation
with various aspects of everyday functional skills perfor-
mance appear similar. Further, negative and cognitive
symptoms have been reported to be correlated in their
severity in cross-sectional assessments of patients with
schizophrenia. Inaddition, theyare reportedtobe uncor-
related with the same features of illness, namely, the
cross-sectional severity of psychotic symptoms.
The question is whether the data regarding the cross-
sectional relationship between negative and cognitive
symptoms suggest that the two are intrinsically related
to each other. If they are, there are important etiological
and treatment implications, in that it may not be possible
to develop treatments that specifically target one symp-
of negative and cognitive symptoms that blur the concep-
tual boundaries between these constructs, and the corre-
lation between cognitive and negative symptoms may
vary as a function of the definition of the negative symp-
toms construct. Negative symptoms are typically defined
in terms of clinical observations of behavioral features,
while cognitive symptoms are defined in terms of perfor-
mance on various tasks. Negative symptoms also appear
to be more etiologically complex than cognitive impair-
ments, in that psychosocial and environmental factors
may impact on the expression of negative symptoms.
Models of the Relationship of Cognitive and
In this article we provide a perspective on the issues
regarding how to determine the ‘‘true’’ relationships
between these variables; we evaluate the impact that
variation in definition of the different symptoms on
the correlation between negative and cognitive symp-
toms; and we provide 4 theoretical models regarding
the nature of the relationships between negative and cog-
these 2 dimensions are in fact identical features of the ill-
ness, or alternate manifestations of the same basic under-
lying process, and would therefore be improved by the
same treatments. The second model holds that these fea-
tures of the illness are, in fact, separable but that they
share similar underlying etiological factors, which leads
to observed correlations between variables and suggests
that treatments for one may also impact the other.
1To whom correspondence should be addressed; e-mail:
Schizophrenia Bulletin vol. 32 no. 2 pp. 250–258, 2006
Advance Access publication on October 12, 2005
? The Author 2005. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: email@example.com.
The third model proposes that each of these symptom
dimensions has a separate etiology but that these etiolo-
gies might be related, which would suggest that treat-
ments for one domain might impact the other, but not
to the same extent as in Model 1 or 2. The final model
views these symptom dimensions as distinct from each
other, with separate etiologies. Thus, correlations be-
tween these domains, if detected, are influenced by mea-
surement and definitional issues or ‘‘third variable’’
relationships with other features of the illness, which
could induce an observed correlation that is actually
We will evaluate the extent to which these models are
supported by the data and what kind of data are needed
in order to further clarify the issue of the potential differ-
entiation between these 2 aspects of schizophrenia.
Clarification of this matter is, of course, particularly
important from the perspective of treatment of these
different features of the illness.
Background Issues Regarding Negative and
Definitions of Negative Symptoms.
addressed elsewhere in this issue, some brief discussion
of the implications of the varying definitions of negative
symptoms is important. Following from the early defini-
tions of Hughlings-Jackson, negative symptoms reflect
a pathological deficit, representing the absence of some
normal functions. It may be easier to define the presence
of some abnormal behavior, belief, or perceptual experi-
ence (ie, positive symptoms) than the relative absence of
While this topic is
normal experience. For instance, some of the domains
currently considered negative symptoms are more easily
delineated and defined than others. While the absence of
normal affective expression or experience can be quanti-
fied and falls within the classical realm of negative symp-
toms, it becomes more difficult to straightforwardly
decide if other behavioral deficits should be referred to
as negative symptoms, as cognitive deficits, or as limita-
tions in everyday life skills. For instance, should reduced
memory performance, concentration ability, or problem-
solving aptitude, even if assessed clinically rather than by
performance on tests, be considered a negative symptom
or a cognitive deficit? Likewise, should deficits in social
competence (as compared to social motivation) or in the
specific performance of occupational skills (as compared
to motivation to seek employment) be considered nega-
tive symptoms? Should behaviors directly resulting from
or maintained by extrinsic factors be considered negative
symptoms (eg, what role do social limitations/barriers
play in social withdrawal and avolition)? If the bound-
aries of negative symptoms are expanded to include cog-
nitive functioning, the correlation between negative
symptoms and other aspects of cognition will be in-
creased, due to the fact that many cognitive abilities
are themselves intercorrelated. While we are not offering
special answersto these questions,which are addressedin
otherarticles in thisissue,wewill evaluatesomedata sug-
gesting that variations in the definition of negative symp-
toms are associated with variation in the correlations
between performance deficits on neuropsychological
(NP) tests and the severity of negative symptoms.
Cognitive and negative symptoms have
several, apparently similar features. These include onset,
temporal course, correlations with other aspects of the
illness, and prognostic importance. Each will be de-
present prior to the diagnosis of psychotic symptoms.1–4
Considerable evidence also indicates that cognitive
impairments are present in cases well before the onset
of psychotic symptoms.2,5As a group, future schizophre-
nia patients manifest cognitive impairments of a magni-
tude of about one-half a standard deviation compared
with controls. The large majority of future patients, how-
ever, do not have extraordinarily poor premorbid social
of intellectual abilities—ie, having a premorbid IQ
greater or equal to 85. Thus, both cognitive and negative
symptoms could be reasonably characterized as ‘‘early
symptoms,’’ and these may also be conceived as the indi-
cators of the developmental (ie, premorbid to prodromal)
component of schizophrenia.
Deficits in social and emotional functioning are
Model 1: Overlapping or nested
Model 2: Common etiology
Model 3: Separable but related etiologies
Model 4: Independent but related due to (a)
overlapping measurements or definitions or (b) shared
correlations with distal measures.
Fig. 1. 4 Theoretical Models of the Nature of the Relationships
Between Negative and Cognitive Symptoms.
Negative Symptoms and Cognition
nia tend to vary over time in most patients. This was
true even prior to the neuroleptic treatment era because
some patients recovered from their psychotic episodes,
experiencing spontaneous remission.6Currently, even
chronic patients often have a variable course of psychotic
symptoms, with the longitudinal correlations close to
zero.7In contrast, the longitudinal stability of negative
and cognitive symptoms is considerably greater, leading
some to conclude that both are ‘‘trait’’ features of schizo-
phrenia. Even in cases where there is relative remission of
psychotic symptoms, negative and cognitive symptoms
are often found to be persistent.8Thus, cognitive and
negative symptoms appear to share a similar course. Sim-
ilar courses do not provide evidence of similar origin of
symptoms and could even suggest that both types of
symptoms are influenced by similar external factors
rather than similar illness-related factors. Further, there
is some evidence that negative symptoms may vary as
a function of substance abuse history, with patients
who abuse substances having greater variability in their
symptoms than nonabusers.9Interestingly, more severe
cognitive impairments were associated with more stable
negative symptoms in that study.
Psychotic symptoms in schizophre-
ative symptoms also have similar relationships to other
symptoms and features of the illness. For example, the
typical cross-sectional correlation between the severity
of negative and cognitive symptoms and the severity of
positive symptoms is low to zero.10–11This would not
be surprising, as noted above, because the typical course
of psychotic symptoms is variable over time, and both
cognitive and negative symptoms appear to be more tem-
porally stable. As a result, even within the same patient,
the correlation between positive symptoms and the other
two domains would be expected to be variable.
Cognitive and neg-
is the relatively similar relationship of negative and
cognitive symptoms and both global and specific indica-
tors of prognosis and everyday life skills. For instance, it
has been appreciated for years that the presence of neg-
ative symptoms early in the illness is associated with
a more adverse course, including more psychotic epi-
sodes12and greater impairment in adaptive life skills.13
Patients who are completely disabled and rely on others
for their survival are more likely to have more severe
negative symptoms than less disabled patients, while
the severity of positive symptoms is similar across these
groups.14Further, patients who meet criteria for the
deficit syndrome have more severe functional impair-
ments and more generalized disability than nondeficit
Similar relationships between course of illness, dis-
ability, and cognitive impairments have been detected.
Even moreimportant, however,
For instance, cognitive impairments early in the illness
also predict a more adverse course of illness and greater
lifelong disability.12In fact, cognitive deficits have been
shown to be the consistently largest cross-sectional
predictor of deficit in specific functional skills in schizo-
phrenia.16–17So, the concurrent correlations of negative
and cognitive symptoms appear to be quite similar, and
from the perspective of concurrent validity, negative and
cognitive symptoms appear to have very similar valida-
tors. However, similar relationships between outcome
and symptoms can be multiply determined. As noted
above, the presence and severity of cognitive impair-
ments can influence the presentation of negative symp-
toms. Further, as also noted above, negative symptoms
have the potential to be more multiply determined than
cognitive deficits. If cognitive impairments led to dis-
ability, it is at least theoretically possible that apathy
and disinterest might be the result of this disability
and not the cause.
when examined cross-sectionally, the severity of negative
and cognitive symptoms are correlated. These findings
are relatively consistent across age and the course of
the illness, from the first episode18to patients with
a chronic course of illness and extended institutional
stay. These correlations are generally moderate and in
the range of r = .30. For instance, at the time of the first
episode, moderate correlations are found between the
majority of cognitive domains and affective flattening,
alogia, and apathy as measured with the Scale for As-
sessment of Negative Symptoms (SANS),19versions of
the Positive and Negative Syndrome Scale (PANSS)
factor-analytically derived negative symptom domain,20
andthePANSS summednegativescale.21A studyofcon-
secutively admitted hospitalized patients found modest
negative correlations between severity of negative symp-
toms and performance on list-learning, paired-associate
and paragraph memory, set shifting, and verbal flu-
ency.22Associations between negative symptoms with
verbal fluency and set shifting deficits are found in
clinically stable patients as well.23Somewhat different
correlations with negative symptoms were found in
higher functioning (ie, community-dwelling) schizophre-
nia patients, where verbal learning and verbal fluency,
but not set shifting, as measured with the Trail Making
Test, part B, were correlated with negative symptom se-
verity.24However, some of the variance in these patterns
of correlations may be related to the negative symptom
definition and rating methods employed. This level of
correlation has been supported by the results of large-
scale meta-analytic studies, in that the Heinrichs and
Zakzanis25review concluded that symptom severity
has a small to moderate correlation with severity of neu-
Data on Negative
P. D. Harvey et al.
Between Negative and Cognitive Symptoms
tors that influence the correlation between negative and
cognitive symptoms in schizophrenia. Possibly the most
robust of these influences is that of the definition of neg-
ative symptoms employed. As noted above, the breadth
of the definition of negative symptoms ranges quite
widely, from experimental measures of affect, emotion,
and communication, to clinical rating scales that desig-
ative symptoms. Further, some definitions of negative
symptoms carefully distinguish between negative symp-
toms that are primary and those that could be accounted
for by external factors, such as the severity of positive
symptoms or medication side effects.
Patients who meet criteria for the deficit syndrome,
a carefully defined syndrome where extraneous causes
of negative symptoms are excluded, appear to have a spe-
cific signature of cognitive impairments. Deficit patients
had greater impairment than nondeficit patients in func-
tions typically attributed to the frontal and parietal
cortex and similar patterns of performance on tests sensi-
tive to dysfunctions in the temporal cortex.26Thus, the
correlation between negative symptoms and cognitive
impairments may be contingent on primary versus sec-
ondary nature of the negative symptoms seen in the
patients. This may be consistent with the results of
Lysaker et al.,9who found that the stable negative symp-
tom severity, as is seen in the deficit syndrome, was
associated with increased cognitive impairments and
found less potential influence of extraneous factors such
as drug abuse.
One of the most commonly used clinical rating scales
for schizophrenia is the PANSS.27This scale examines
30 different symptoms of schizophrenia. Interestingly,
several aspects of the illness that clearly appear to be cog-
nitive in nature (eg, deficits in abstract thinking, stereo-
typed thinking, poor attention) are defined as negative
or general symptoms of schizophrenia by the PANSS
and contribute to total scores on those symptom dimen-
of schizophrenia as negative symptoms, the PANSS does
not have an extensive assessment of reduced verbal pro-
ductivity, as compared with other clinical rating scales,
which might also impact its correlational structure. Fac-
tom factor of the PANSS as initially defined. However,
a negative symptom factor emerges from typical explor-
atory factor analyses of the PANSS, at least one of which
difficulty in abstract thinking item.28
The other commonly used rating scale of negative
symptoms, the SANS,29also has some item definitions
that have the potential to impact correlations with NP
There are several fac-
performance. For instance, the SANS designates a num-
ber of social, occupational, and educational performance
deficits as negative symptoms. Since NP performance has
been shown to be consistently related to impairments in
social, occupational, and educational outcomes, designa-
ative symptom severity. Further, the SANS also designa-
tes attentional abnormalities as negative symptoms. One
of the problems with clinical ratings of cognitive symp-
toms on negative symptom scales is that clinicians’
ratings of cognitive dysfunction in schizophrenia are
often poorly overlapping with NP performance mea-
sures,20,30so it is unclear what clinicians might be rating.
Correlations between similar domains of cognitive
abilities and negative symptoms can vary depending on
the symptom rating scale used. For example, Berman
et al.23reported that problem-solving deficits measured
by the Wisconsin Card Sorting Test (WCST), as well as
impairments in processing speed, were correlated with
the severity of PANSS negative subscale scores. Verbal
fluency deficits did not appear to be correlated with
PANSS negative subscale scores in that study. In con-
trast, other research has found that negative symptoms
functioning, estimated by WCST performance, verbal
memory, and verbal fluency.31While Bozikas et al.24
found that memory deficits and semantic knowledge
were correlated with negative symptoms rated by the
PANSS, they found that executive functioning was
not. One possibility for these differences in correlations
across studies is that the SANS has a more extensive as-
sessment of verbal underproductivity (ie, alogia) than the
PANSS, which uses a single item. Further, patients who
refuse to talk because they are concerned about the
content of the information are rated the same on this
PANSS item as patients whose failure to talk is a not
due to refusal.
symptoms require inferential ratings of various negative
symptoms, including affective experience and motiva-
tion, and these inferences are necessarily limited by the
patients’ level of communication, meaning that patients
who are less verbally productive may also be difficult
to rate on other symptoms. It is possible, however, to
measure affective expression directly. Direct measures
have the benefit of not relying on self-report and not
changes relevant to negative symptoms have found
results that suggest minimal correlations between direct
measures of emotional experience and neuropsychologi-
For instance, Blanchard, Kring, and Neale32found es-
sentially no significant correlations between any aspects
of a neuropsychological assessment battery and direct
Most ratingscalesfor negative
Negative Symptoms and Cognition
measures of facial affect expression. These affect expres-
sion measures, however, were found to be well correlated
with other direct experimental measures of affect expres-
sion and perception. This study was particularly system-
atic in that neuropsychological measures of left and
right hemisphere functioning, as well as frontal lobe
functioning, were included. Alpert et al.33suggested that
the general patterns of correlation between cognitive
impairments and negative symptoms may be related to
the tendency of raters to focus on global clinical features
and then rate the individual items in the rating scales
according to their global impression, instead of the re-
verse (ie, generating a global scale from the sum or aver-
age of the individual items). If this is the case, raters may
be sensitive to global impairment features in the emo-
tional/negative symptom domains or in the cognitive
impairment domains, influencing their ratings in both
areas and subsequent correlations as well.
Specificity of the Negative/Cognitive Relationship.
toms are most strongly correlated with NP performance
as well. Bilder et al.34reported that performance scores
on a comprehensive neuropsychological battery were
more strongly correlated with disorganized than with
negative symptoms. Similarly, Liddle35found that dis-
organization syndrome was associated with different
cognitive impairments than the psychomotor poverty
syndrome, suggesting that negative and cognitive symp-
toms are not intrinsically liked.
years ago, there are relatively few longitudinal studies
of the correlations between negative and cognitive symp-
toms. The few studies that have been published are
largely based on a large cohort of very severely ill, chron-
ically institutionalized patients in the Mt. Sinai cohort.
These data may not be representative of the course of
negativesymptomsin better outcomepatients.Still, there
may be some information to guide our evaluation of the
relationships between negative and cognitive symptoms.
In the first, we37reported that negative and cognitive
symptoms were correlated with each other at each of 2
assessments in a 1-year follow-up, with no significant
cross-lagged correlations between the two variables.
One reason for the lack of longitudinal correlations
may be the stability and resulting lack of variance of
both of these variables across the short follow-up: there
is little change and little possibility of correlation of the
change scores. Longer follow-ups (up to 6 years), where
patients declined in the cognitive functioning, again
found the same pattern, however: significant correlations
at each ofthe successive assessments and little correlation
ter outcome patients, Hughes and colleagues40found es-
sentially the same results: correlations between negative
As noted by Addington36five
symptoms and cognitive deficits at time 1 but a failure of
negative symptom change to predict cognitive change at
follow-up, regardless of how the negative symptom di-
mension was defined. In a treatment study of initially
clinically stable patients with schizophrenia,41clinical
improvements in negative symptoms were detected, as
were improvements in NP performance. While negative
symptom changes were correlated with other aspects of
clinical change (ie, positive and disorganized symptoms,
hostility), there was no correlation between improve-
ments in negative symptoms and cognitive performance.
Thus, the limited data from longitudinal studies of var-
ious samples of patients with schizophrenia, as well as
a single treatment study, have indicated that changes
in cognition and negative symptoms can be dissociated.
Interestingly, functional declines were associated with
cognitive declines in the studies of poor outcome geriatric
patients, while the course of negative symptoms was un-
correlated with functional declines.
Relationships with Distal Outcomes.
cross-sectional studies have suggested that differential
correlations between negative and cognitive features of
the illness and everyday outcomes can be identified. In
fact, in 2 separate studies, it has been shown that when
negative and cognitive symptoms are considered simul-
taneously, cognitive impairment is more strongly cor-
related with real-world outcomes than are negative
symptoms.42,43As noted above, cognitive change, but
not negative symptoms change, predicted functional
decline. While this finding might have important impli-
cations for improving functional outcomes, there may
also be implications regarding the relationship between
negative and cognitive symptoms.
A regression result showing that one variable is much
more important as a predictor than the other could be
obtained if negative and cognitive symptoms were actu-
ally very highly correlated, or even alternative measures
of the same ‘‘true construct’’ (see Models 1 and 2). To
produce this outcome, which was obtained with regres-
sion analyses, the measure of negative symptoms would
need to be only slightly less correlated with everyday
functioning than cognitive impairments. It is also possi-
related in ‘‘true’’ severity with each other, with other
correlational relationships a statistical artifact. This out-
come would be expected if Model 4 was true, and the cor-
relation between negative and cognitive symptoms was
induced by their joint, but independent, associations
with a distal measure such as real-world functional out-
comes. Finally, it is possible that negative and cognitive
symptoms have different patterns of influence on real-
world outcomes. It could be that NP performance is as-
sociated with the ability to perform everyday living skills,
while negative symptoms are associated with the likeli-
hood of performing these skills.
P. D. Harvey et al.
We44used confirmatory path modeling to examine
the partial correlations between several different aspects
of schizophrenia, including ratings of everyday func-
tioning generated by case management personnel, per-
formance on a comprehensive NP battery, scores on a
performance-based measure of functional skills (the
UCSD performance-based skills assessment [UPSA]45),
positive and negative symptoms measured by the
PANSS, and self-reported depression. Best-fitting path
models were developed and used to determine the nature
of the relationship between these features of schizophre-
nia and everyday functioning. While these results are
presented in detail elsewhere, they were informative in
terms of providing some intriguing insights about our
4 models of cognitive and negative symptoms. Zero-
order correlations between PANSS negative symp-
toms and NP performance were quite similar to those
reported in previous studies (r = –.32). However,
when the simultaneous relationships between these var-
iables were examined with path modeling, a more com-
plex picture emerged. The most consistent predictor of
several different aspects of everyday functioning was
skills competence (ie, the capacity to perform these skills
in an analog setting). However, negative symptoms were
directly correlated with everyday functioning in the
domains of social performance and everyday life skills.
In the path model for social functioning (Figure 2), it
can be seen that when the path coefficients between
NP performance, functional capacity, and negative
symptoms are examined, there is no relationship be-
tween negative symptoms and either NP performance
or functional competence.
These findings suggest not only that negative and cog-
nitive symptoms are discriminable, but that they also
have considerably different functional implications.
The moderate zero-order correlation detected prior to
outcomes. More important, however, is the functional
implications of these findings. NP performance was cor-
related with the ability to perform everyday living skills,
while negativesymptoms were related to the likelihoodof
performing these skills.
Conclusion: Evaluation of the Models
Very few, if any, of the studies reviewed here provide di-
rect or comprehensive evidence about all of the 4 possible
models of the relationship between cognitive and nega-
shows that the existing studies provide stronger support
for Models 3 and 4 than for Models 1 and 2. In the fol-
lowing sections we summarize the evidence pertaining to
each model and indicate the kind of data that is still
needed in order to further assess it.
symptoms are 2 alternate or nested manifestations of the
same basic process. The results of many studies of the on-
set, temporal course, relations to other aspects of the ill-
ness, and cross-sectional correlations between negative
and cognitive symptoms appear on the surface tosupport
suggests that, while both cognitive and negative symp-
toms are related to other aspects of the illness and occur
during the same time frame, the correlation between neg-
ative and cognitive symptoms is limited in magnitude.
Data from longitudinal studies, as well as factor and
path analytic studies, suggest that the 2 symptom dimen-
sions can change independently of the other due to either
treatment or to the natural course of the illness. The ba-
sically small level of correlation between cognitive and
negative symptoms argues that it is unlikely that they
are actually the same phenomenon and suggests that
more complex models may be required to explain the
association between these models.
Model 1 posits that cognitive and negative
liability and stability characteristics of the measures used
to assess negative symptoms. Long-term data regarding
the general stability of negative, as compared with cog-
nitive, symptoms would provide information regarding
the possibility that these are not separable entities.
More information is needed about the re-
cognitiveand negativesymptoms are indeed separatefea-
tures of schizophrenia but that they share similar under-
lying etiology. An example of such an etiology could be
a dysfunction of the thalamus, wherein abnormal activity
in this region would result in cognitive impairments due
to influences on temporal lobe projections and negative
This model appears to be supported by the results of
cross-sectional studies that find moderate correlations
between the severity of these 2 symptom dimensions
and consistent correlations over time in longitudinal
studies. While the lack of longitudinal correlations in
Model 2 puts forward the assumption that
Fig. 2. Negative Symptoms, Cognitive Performance, and
Everyday Skills Performance. Source: Bowie et al.44
Negative Symptoms and Cognition
changes between the 2 domains appears not to support
the model, it should be noted that many illnesses with
ease, have a variable course with not all symptoms of the
illness being present consistently over time.
tive and cognitive symptoms would provide information
about the linkage between these two symptom domains.
correlations with changes in these symptom domains
would be helpful as well.
More studies of the joint course of nega-
negative and cognitive symptoms represent 2 separate
dimensions of the illness. Model 3, however, posits
that each dimension has its own etiology, which in
turn might be related to the etiology of the other dimen-
sion due to outside influences. An example of this type of
cause would be distributed neuropathology, such as
white matter abnormalities, which would differentially
affect brain regions depending on the normal density
of white matter. Thus, pathological changes in com-
pletely separate brain regions could be the cause of the
negative and cognitive symptoms, but the underlying eti-
ologies are related to each other. We believe that Model 3
is supported by existing studies and holds promise for
explaining the observed relations between cognitive
and negative symptoms in schizophrenia. First, most lon-
gitudinal studies suggest a similar yet not overlapping
course of negative and cognitive symptoms. Second, re-
cent studies suggest that cognitive performance is at least
as strongly related to disorganized symptoms as to neg-
ative ones, indicating that cognitive impairments may be
related in severity to multiple features of the illness. Fi-
nally, negative and cognitive symptoms appear to change
at different rates in studies of both the progression and
treatment of the illness, but the overall level of impair-
ment in each of these domains tends to be correlated
at successive longitudinal assessments.
Like Model 2, Model 3 speculates that
Model 2, similar data would be required. Identification
and longitudinal assessment of putative etiological fac-
tors may provide the data required for the critical tests
of these 2 models, combined with carefully defined meas-
ures of negative symptoms and NP tests.
In order to discriminate Model 3 from
as distinct from each other, with independent etiologies.
However, unlike Model 3, Model 4 attributes the ob-
served correlationsbetween negativeand cognitivesymp-
toms to measurement issues and correlations with
Model 4 views the 2 symptom dimensions
distal measures. The fact that deficit syndrome patients
show a different signature of cognitive impairments
than nondeficit patients is also consistent with this inter-
pretation: it may be that the deficit syndrome truly
reflects a different etiology for the illness and for the
associated cognitive impairments as well. Finding that
objective measures of emotional experience are uncorre-
lated with cognitive symptoms is also consistent with
this model. This model is supported by more recent
correlation between negative symptoms and cognitive
impairments is explained by correlations with distal out-
tated by treatments that enhance cognitive functioning.
These interventions, either pharmacologically or rehabil-
itationoriented, mayserveas acriticaltest ofthe discrim-
inability of negative and cognitive symptoms.
In sum, negative and cognitive symptoms of schizo-
phrenia appear to be correlated but potentially separable
domains of the illness. While cross-sectional studies sug-
gest moderate relationships, path modeling suggests that
these 2 symptom domains may have critical differences in
their functional relevance and that their cross-sectional
correlation could be related to independent relationships
with other features of the illness. As the definition of the
negative symptoms construct appears to influence the
correlation with cognitive performance, innovations in
the assessment of negative symptoms may be required
in order to truly answer the questions regarding the re-
lationship of negative symptoms and other aspects of
Evaluation of this model will be facili-
This research was supported by NIMH Grant Number
MH 63116 to Dr. Harvey, the Mt. Sinai Silvio Conte
Neuroscience Center (NIMH MH 36692; KL Davis
PI), and the VA VISN 3 MIRECC.
1. Jones P, Rodgers B, Murray R, et al. Child development risk
factors for adult schizophrenia in the British 1946 birth
cohort. Lancet. 1994;344:1398–1402.
2. Davidson M, Reichenberg A, Rabinowitz J, Weiser M,
Kaplan Z, Mark M. Behavioral and intellectual markers for
schizophrenia in apparently healthy male adolescents. Am J
3. Reichenberg A, Rabinowitz J, Weiser M, et al. Pre-
morbid functioning in a national population of male twins
discordant for psychoses. Am J Psychiatry. 2000;157:
4. Cannon M, Caspi A, Moffitt TE, et al. Evidence for early-
childhood, pan-developmental impairment specific to schizo-
phreniform disorder: results from a longitudinal birth cohort.
Arch Gen Psychiatry. 2002;59:449–556.
P. D. Harvey et al.
5. David AS, Malmberg A, Brandt L, Allebeck P, Lewis G. IQ
and risk for schizophrenia: a population-based cohort study.
Psychol Med. 1997;27:1311–1323.
6. Hegarty JD, Baldessarini RJ, Tohen M. One hundred years of
schizophrenia: a meta-analysis of the outcome literature.
Am J Psychiatry. 1994;151:1409–1416.
7. Putnam KM, Harvey PD, Parrella M, et al. Symptom stabil-
ity in geriatric chronic schizophrenic inpatients: a one-year
follow-up study. Biol Psychiatry. 1996;39:92–99.
8. Harvey PD, Docherty N, Serper MR, Rasmussen M. Cogni-
tive deficits and thought disorder: II. an eight-month follow-
up study. Schizophr Bull. 1990;16:147–156.
9. Lysaker PH, Bell MD, Bioty SM, Zito WS. Cognitive im-
pairment and substance abuse history as predictors of the
temporal stability of negative symptoms. J Nerv Ment Dis.
10. Mohamed S, Paulsen JS, O’Leary D, Arndt S, Andreasen N.
Generalized cognitive deficits in schizophrenia: a study of
first-episode patients. Arch Gen Psychiatry. 1999;56:749–754.
11. Davidson M, Harvey PD, Powchick P, et al. Severity of
symptoms in chronically institutionalized geriatric schizo-
phrenic patients. Am J Psychiatry. 1995;152:197–205.
12. Breier A, Schreiber JL, Dyer J, Pickar D. National Institute
of Mental Health longitudinal study of chronic schizo-
phrenia: prognosis and predictors of outcome. Arch Gen Psy-
13. Fenton WS, McGlashan TH. Natural history of schizophre-
nia subtypes: II. positive and negative symptoms and long-
term course. Arch Gen Psychiatry. 1991;48:978–986.
14. Keefe RSE, Mohs RC, Losonczy M, et al. Characteristics of
very poor outcome schizophrenia. Am J Psychiatry. 1987;144:
15. Buchanan RW, Kirkpatrick B, Heinrichs DW, Carpenter
WT. Clinical correlates of the deficit syndrome of schizophre-
nia. Am J Psychiatry. 1990;147:290–294.
16. Green MF. What are the functional consequences of neuro-
cognitive deficits in schizophrenia? Am J Psychiatry. 1996;
17. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive def-
icits and functional outcome in schizophrenia: are we measur-
ing the ‘‘right stuff’’? Schizophr Bull. 2000;26:119–136.
18. Rabinowitz J, DeSmedt G, Harvey PD, Davidson M. The
relationships between premorbid functioning and symptom
severity as assessed at the first episode of psychosis. Am J
19. Bilder RM, Goldman RS, Robinson D, et al. Neuropsychol-
ogy of first-episode schizophrenia: initial characterization and
clinical correlates. Am J Psychiatry. 2000;57:549–559.
20. Good KP, Rabinowitz J, Whitehorn D, Harvey PD, DeSmedt
G, Kopala L. The relationship of neuropsychological test
performance with the PANSS in antipsychotic naive, first-
episode psychosis patients. Schizophr Res. 2004;68:11–19.
21. Heydebrand G, Weiser M, Rabinowitz J, Hoff AL, DeLisi
LE, Csernansky JG. Correlates of cognitive deficits in first
episode schizophrenia. Schizophr Res. 2004;68:1–9.
22. O’Leary DS, Flaum M, Kesler ML, et al. Cognitive correlates
of negative, disorganized, and psychotic symptom dimensions
of schizophrenia. J Neuropsychiatry Clin Neurosci. 2000;12:
23. Berman I, Viegener B, Merson A, Allan E, Pappas D, Green
AI. Differential relationships between positive and negative
symptoms and neuropsychological deficits in schizophrenia.
Schizophr Res. 1997;25:1–10.
24. Bozikas VP, Kosmidis MH, Kioperlidou K, Karavatos A.
functioning in schizophrenia. Compr Psychiatry. 2004;45:
25. Heinrichs RW, Zakzanis KK. Neurocognitive deficit in
schizophrenia: a quantitative review of the evidence. Neuro-
26. Buchanan RW, Strauss ME, Kirkpatrick B, Holstein C,
Breier A, Carpenter WT. Neuropsychological impairments
in deficits vs. nondeficit forms of schizophrenia. Arch Gen
27. Kay SR. Positive and Negative Syndromes in Schizophrenia.
New York: Brunner/Mazel; 1991.
28. White L, Harvey PD, Opler L, Lindenmayer JP. Empirical as-
sessment of the factorial structure of clinical symptoms in
schizophrenia: a multisite, multimodel evaluation of the fac-
torial structure of the Positive and Negative Syndrome Scale.
29. Andreasen NC. Scale for assessment of negative symptoms.
University of Iowa; 1981.
30. Harvey PD, Serper M, White L, et al. The convergence of
neuropsychological testing and clinical ratings of cognitive
impairment in patients with schizophrenia. Compr Psychiatry.
31. Addington J, Addington D, Maticka-Tyndale E. Cognitive
functioning and positive and negative symptoms in schizo-
phrenia. Schizophr Res. 1991;4:123–134.
32. Blanchard JJ, Kring AM, Neale JM. Flat affect in schizo-
phrenia: a test of neuropsychological models. Schizophr
33. Alpert M, Shaw RJ, Pouget ER, Lim KO. A comparison of
clinical ratings with vocal acoustic measures of flat affect
and alogia. J Psychiatr Res. 2002;36:347–353.
34. Bilder RM, Mukherjee S, Rieder RO, Pandurangi AK. Symp-
tomatic and neuropsychological components of defect states.
Schizophr Bull. 1985;11:409–419.
35. Liddle PF. Schizophrenic syndromes, cognitive performance,
and neurological dysfunction. Psychol Med. 1987;17:49–57.
36. Addington J. Cognitive functioning and negative symptoms
in schizophrenia. In: Sharma T, Harvey PD, eds. Cognition
in Schizophrenia. New York: Oxford University Press; 2000:
37. Harvey PD, Lombardi J, Leibman M, et al. Cognitive impair-
ment and negative symptoms in schizophrenia: a prospective
study of their relationship. Schizophr Res. 1996;22:223–231.
38. Friedman JI, Harvey PD, McGurk SR, et al. Correlates of
change in functional status of institutionalized geriatric
schizophrenic patients: focus on medical co-morbidity. Am
J Psychiatry. 2002;159:1388–1394.
39. Harvey PD, Bertisch H, Friedman JI, et al. The course of
functional decline in geriatric patients with schizophrenia:
cognitive, functional, and clinical symptoms as determinants
of change. Am J Geriatr Psychiatry. 2003;11:610–619.
40. Hughes C, Kumari V, Soni W, et al. Longitudinal study of
symptoms and cognitive function in chronic schizophrenia.
Schizophr Res. 2003;59:137–146.
41. Harvey PD, Green MF, Bowie CR, Loebel A Factor struc-
ture of clinical change in schizophrenia: association with
improvements in cognitive functioning. Under review.
42. Velligan DI, Mahurin RK, Diamond PL, et al. The functional
significance of symptomatology and cognitive function in
schizophrenia. Schizophr Res. 1997;25:21–31.
Negative Symptoms and Cognition
43. Harvey PD, Howanitz E, Parrella M, et al. Symptoms, cogni- Download full-text
tive functioning, and adaptive skills in geriatric patients with
lifelong schizophrenia: a comparison across treatment sites.
Am J Psychiatry. 1998;155:1080–1086.
44. Bowie CR, Reichenberg A, Patterson TL, Heaton RK,
Harvey PD. Determinants of real world functional perfor-
mance in schizophrenia: correlations with cognition, func-
tional capacity, and symptoms. Am J Psychiatry. In press.
45. Patterson TL, Goldman S, McKibbin CL, et al. UCSD
performance-based skills assessment: development of a new
measure of everyday functioning for severely mentally ill
adults. Schizophr Bull. 2001;27:235–245.
P. D. Harvey et al.