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.
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Neuro-cognitive issues in schizophrenia.
by D.J. Jaffe
“Thinking” symptoms may be more important than “positive” or “negative” ?symptoms in determining outcomes for people with schizophrenia.
The following is taken from a speech by Dr. Judith Jaeger at the AMI/NYS Conference in 1980s. The research has become a lot clearer that Dr. Jaeger was right. The National Alliance for Research on Schizophrenia and Depression (narsad.org) is funding her research.
Dr. Jaeger is a ‘neuro-psychologist’ who studies the effect of “neuro-cognitive” deficits in individuals with schizophrenia. This is a new, ?and emerging field in schizophrenia research. Basically, we used to refer to ?individuals with Schizophrenia as having two clusters of symptoms: positive ?(hallucinations, psychosis, etc.) and negative (withdrawal, apathy, etc.).
While it has long been noticed that individuals with schizophrenia also developed ?problems thinking (performing simple tasks) this was historically thought to ?be a side effect of the positive and negative symptoms (or medication) and not a cluster of symptoms in their own right. This is changing. These problems are now described ?as neurocognitive deficits.
Dr. Jaeger claims that severity of positive and negative symptoms has little to do with whether or not an individual with schizophrenia can function successfully ?in the community. She says there is a large body of research that shows that people with differing levels of symptoms have differing abilities to be self-sufficient. Therefore she concludes, something other than the presence ?of positive or negative symptoms has to account for why some people can live alone, and others can’t. She believes the factor is ‘neurocognitive’ ?deficits: the ability to think clearly.
For many years, people have studied neurocognitive deficits in people with ?brain injuries, but only recently has this research been applied to individuals with schizophrenia. She notes that most psychiatric ?rehabilitation programs focus on ‘skills training’ but do not focus at all on?the underlying disease which is responsible for the impairments rehab ?training is trying to address.
She points out that Vocational Rehab only works for 27% of individuals with schizophrenia, and of the remaining, only 1/2-1/3 of ?those who were ‘successes’ are working two years later. She calls vocational rehabilitation ?a “prosthesis for the frontal lobe”, meaning it may help (and is therefore ?good) but does not address the core issue (the thinking problems associated ?with frontal lobe damage). From this she concludes that vocational training ?and/or rehab that fails to address the underlying neurocognitive deficits is ?not the optimal approach.
There are four kinds of neurocognitive deficits found in people, including ?those with schizophrenia.
- 1. Attention deficits
- 2. Memory deficits
- 3. Executive function deficits
- 4. Neuromotor deficits
Dr. Jaeger has focused on Executive Function. This is defined as the ability ?to ‘plan, organize, sequence, modulate (start/stop)’ activities. It is the ?Executive Function which is most often impaired in individuals with schizophrenia. In ?order to test her hypothesis, that problems in executive function are more ?important than positive or negative symptoms in determining how well someone ?functions, she used a Wisconsin Card Sort, which tests executive function.
In this test, an individual is given a stack of cards that can be sorted ?either by color, number or shape. The individual is asked to sort the cards. ?If they do it by number, the tester says they are wrong. Most people will?then attempt to sort by either size or shape. Again, the researcher says ?they are wrong. Finally, the person will sort the cards by whatever they haven’t already tried. Most 12 year olds can succeed at this, as can most ?people who do not have, but later develop schizophrenia.
She found that even when you account for positive and negative symptoms, the ability to perform well on the Wisconsin Card Sort is a much better predictor ?than any other of how well people can function. It predicted better than ?symptoms, better than presence of possible symptoms, negative symptoms, attention, and language or memory deficits.
Having come to the belief that Executive Function deficit is the most ?important factor in determining how well someone functions in the community, ?she is now working to determine whether or not Executive Functioning deficits ?can be improved or compensated for. She has two hopeful lines of pursuit:
- 1. Electronic Techniques
- 2. Mental Exercises.
Electronic techniques use things like watches that beep, personal organizers, and automated telephone calls as prosthetic devices to help people cope with Executive Function Deficits. This has been done in people with brain ?injuries.
The second area of investigation has to do with using mental exercises to rebuild the brain. She believes that sustaining and modulating attention is a big problem for people with Schizophrenia. (If you can’t pay attention, it’s hard to do anything.)
There are numerous studies that show that a large portion of the brain is involved in attention deficits. The brain has numerous redundant systems to deal with attention. She believes that it would be unusual for all these multiple redundant systems to be simultaneously broke, and therefore a way can be developed to have some of the systems compensate ?for others. She is testing a “Attention Processing Training Program” developed in Washington. It is an intensive 10-week program using ?audio tapes to help someone develop better attention. The tapes say “Press a button when you hear such and such”. Later tapes require you to press the ?button when you hear a more complicated series. The hope is that by increasing the difficulty of what you have to listen for, before you press the button, that attention deficits can be eliminated or minimized.
It was a fascinating presentation on an area that has long interested me (My own sis-in-law, a former top performer in H.S., now has difficulties with simple tasks like putting on and tying shoes. This occurs regardless ?of whether the meds are or are not controlling any negative symptoms she may ?have and if she is or is not taking them.).