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Briefing Paper
COGNITIVE IMPAIRMENT: A MAJOR PROBLEM FOR
INDIVIDUALS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER
SUMMARY: It has been observed for many
years that some individuals with schizophrenia and manic-depressive illness (bipolar
disorder) cannot think clearly. Studies since 1980 have identified two major reasons why
this is so: (I) cognitive impairment, and (II) lack of awareness of illness (anosognosia).
This briefing paper will summarize the studies done on cognitive impairment.
* * *
Does cognitive impairment exist in
schizophrenia and bipolar disorder?
Cognitive impairment was once an underappreciated
feature of schizophrenia. It was considered an artifact of patients’ symptoms,
attention, or motivation problems, but this turned out to be incorrect. Since the 1980s,
it has come to be seen as a core feature of the disorder, reliably present in the majority
of patients, independent of such positive symptoms as delusions and hallucinations, and a
major cause of poor social and vocational outcome (Goldberg et al., 1990;Green, 1996). It
is also reliably associated with the neurobiology of the disorder (Goldberg et al.,
1995.). It is trait-like and present throughout the course of the illness. Thus,
impairment is stable over short (months) and long (years) intervals (Heaton et al., in
press).
Cognitive impairments in schizophrenia are not epiphenomena. That is, they are not
secondary to psychological issues that involve delusions, distracting effects of
hallucinations, or gross motivational defects. This has been shown by several approaches.
First, correlations between symptoms and cognition are weak in schizophrenia (they are,
however, very strong in bipolar disorder). Second, critical impairments in working memory
and executive functions in schizophrenia do not respond to teaching or cognitive
rehabilitation to a marked degree. Third, symptoms and cognition can be dissociated using
pharmacological tools: A study of clozapine has found that while symptoms showed
significant improvement over a one-year interval, cognitive impairment remained stable and
marked.
Cognitive impairment in bipolar disorder is coming under increasing scrutiny. It is
undeniably the case that cognitive impairment is present in a minority of bipolar
patients. At times it may be severe and approach the level of impairment found in
schizophrenia (McKenna, 1994). Generally, however, it is more state-like and thus most
likely to be present when psychiatric symptoms are in evidence (e.g., dysphoria,
anhedonia, anergia in depression, grandiosity, expansiveness, pressured speech, racing
thoughts, gross overactivity in mania) (Goldberg, 1999). In other words, it waxes and
wanes in concert with the clinical symptoms of bipolar disorder. When present, it may
account in part for the poor judgment and decision making that afflicts some patients with
bipolar disorder.
Does cognitive impairment change over
time?
Cognitive impairment in schizophrenia is stable and
lifelong. It does not remit, even if other symptoms like hallucinations and delusions are
significantly attenuated. In most cases, patients have subtle attenuations of cognitive
abilities prior to the onset of the disorder. These become pronounced around the time the
illness commences, after which they remain more or less stable over many years.
The time course of cognitive impairment in bipolar disorder is not well studied.
Certainly, some functions appear to tightly co-vary with clinical improvements, including
measures of executive function and verbal fluency (McGrath et al., 1997). Some deficits
have been shown to be more persistent, though it is unclear if cognitive improvement
simply lags behind normalization of mood.
The nature of cognitive impairments in
schizophrenia and bipolar disorder
Schizophrenia may have a relatively unique set of
cognitive impairments. Working memory is used for everything: remembering a phone number,
comprehending a complex verbal passage, planning a talk, an outing, or a day’s
activities, and generating a novel strategy to solve a problem. In schizophrenia, it is
consistently impaired. Long-term memory involving the acquisition and recall of new
information may be impaired at relatively severe levels (Saykin et al., 1991). Patients
with schizophrenia also show reduced mental speed and reaction time. This pattern of
deficits implicates frontal-temporal regions and possibly their connectivity or
interactions.
Working memory may be the core deficit in schizophrenia in that it is present
irrespective of whether IQ is compromised or preserved. It can be thought of as the
mind’s blackboard: Information temporarily resides there and is used in the service
of planning a response, after which it is erased when new, more relevant information
becomes available. Impairments in working memory take the form of frank failures to hold
information over short periods of time, for example, 10 seconds; failures to show mental
flexibility (with resulting perseveration); or difficulties in maintaining readiness to
process specific and salient contextual information and holding on to information in the
face of interference (i.e., while doing several tasks simultaneously). Prefrontal cortical
regions in the brain are thought to play a crucial role in working memory.
There are several views of cognitive impairment in bipolar disorder. Some investigators
have suggested that tasks that demand the most effort or speed are difficult for patients
with bipolar disorder. Another set of research findings indicates that patients with
bipolar disorder suffer from right hemisphere cortical involvement that affects different
types of visual perceptual processing for recognizing objects and determining orientations
in space, as well as impacting on lateralized neural systems that regulate mood. None of
these models has received consistent support in the scientific literature.
In general the degree of cognitive impairment in schizophrenia is more severe than in
bipolar disorder and involves more cognitive domains. Cognitive impairment in
schizophrenia is less strongly correlated with degree of psychiatric symptoms and so is
more "trait-like" and less "state-like."
Effect of cognitive impairment on
performance
It is often the case that schizophrenia precludes
expert performance in science, the arts, and athletics. Bipolar disorder clearly does not.
In fact, it has sometimes been associated with creativity, though the reasons for this are
unknown. One explanation for this observation is the differing degrees of cognitive
impairment between the two disorders.
Cognitive impairment in schizophrenia, especially in verbal memory and working memory,
is a strong predictor of outcome. Unexpectedly, the more florid positive symptoms of
schizophrenia, such as hallucinations and delusions, are not good predictors of outcome.
The relationship of cognitive impairment outcome in bipolar disorder is unclear.
Moreover, studies of cognitive impairment in bipolar disorder often have not taken into
account state changes. Thus, differences in cognition in the manic state, depressed state,
or euthymic (normal) state have not been dissected. These areas should be researched
further.
What are the effects of medications on
cognition in these disorders?
Novel or newer antipsychotics such as risperidone,
clozapine, and olanzapine seem to produce gains in cognition, while older, typical
neuroleptic medications (e.g., haloperidol, fluphenazine) do not (Keefe et al., 1999).
This improvement may reflect diminution in extrapyramidal side effects caused by typical
high potency neuroleptics that might slow an individual because of the impact on motor
systems. Or it might reflect more effective symptom reduction by the atypicals, or direct
cognitive enhancement through their effects on a variety of neurotransmitters, their
receptors, and gene expression. It is important to recognize that, even when newer
antipsychotic medications improve cognition, they still do not normalize it;
unfortunately, many patients have residual impairments.
Does lithium cause cognitive impairment in bipolar disorder? There have been consistent
findings that lithium has mild but adverse effects on long-term memory that involves the
acquisition of new information (Judd, 1995). It is possible that the newer mood
stabilizers (usually drugs with anticonvulsant properties, such as carbamezepine,
depakote, and neurontin) will have less marked effects on cognition, especially memory.
Cognition and brain mapping
It is important to note that many of the cognitive
impairments in schizophrenia, including those of working memory and episodic memory, have
been mapped onto the brain. That is, they do not exist in a vacuum but rather reflect
abnormal neurophysiological processes. Thus, in a variety of PET and fMRI procedures
measuring blood flow, a surrogate marker for brain metabolism, patients with schizophrenia
have variously, depending on tasks, shown to display frontal hypoactivation (correlated
with the degree of abnormal task performance), inefficient physiological responses that
are miscalibrated to the amount of effort involved in a task, and differences in the
dynamics of neural networks such that patients may show over-activation in one region and
under-activation in another. Cognitive impairment in schizophrenia has also been found to
correlate with the degree of structural brain abnormalities, including increased
ventricular size and reduced medial temporal lobe volumes. Detailed analyses of bipolar
neurophysiology in the context of cognitive challenge have not been done.
Direct comparison ofschizophrenic and
bipolar cognitive impairment
Direct comparisons of patients with schizophrenia
and those with bipolar disorder indicate that patients with schizophrenia have more severe
and widespread deficits. Nevertheless, a subgroup of institutionalized patients with
bipolar disorder appears to have chronic and severe cognitive impairments (Harvey et al.,
1997).
One important measure that discriminates between patients with schizophrenia and those
with bipolar disorder is intelligence. In general, patients with schizophrenia exhibit a
10-point decline of intelligence once their illness begins. That is, patients with
schizophrenia have normal or near normal IQ’s premorbidly but, even during the early
phases of their illness, exhibit a marked attenuation in intellectual function. In
contrast, patients with bipolar disorder generally are able to maintain their IQ level.
This is clinically significant and suggests that patients with schizophrenia will be less
attentive and slower, have less mental precision in day-to-day cognitive operations, and
may have difficulties in bringing their knowledge base to bear on social problems. In
contrast, patients with bipolar disorder do not exhibit such global decline in
intellectual efficiency.
Degree1 of Impairment in Schizophrenia and Bipolar Disorder
(from Goldberg, 1999; Goldberg unpublished)
| Test |
Schizophrenia |
Bipolar
Disorder |
| IQ |
++ |
- |
| Memory |
+++ |
+ |
| Attention |
++ |
+ |
Card Sort/
Perseveration |
+ |
- |
| Visual Process |
+ |
++? |
1 + = Effect Size < .2
++ = .2< Effect Size < .5
+++ = Effect Size > .8
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