by Philip D. Harvey, PhD

Dr. Harvey is Professor, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

Symptom Dimensions in Schizophrenia

Since the earliest conceptions of schizophrenia, dating back to the 19th century, there has been a focus on the heterogeneity of the illness. Both Kraepelin and Bleuler agreed that schizophrenia had many different variants or subtypes and that the condition may be the result of more than one illness process. Kraepelin’s focus was on the subtypes of schizophrenia, describing classical subtypes that are still contained in the DSM today. Blueler focused on the fact that patients with schizophrenia present with an array of different symptoms, even if there is core pathology reflected by the fundamental symptoms (affect, autism, associations, ambivalence).

Since that time, the diversity of schizophrenia has been investigated through studies of symptomatic structure, often using factor analysis. Symptoms in schizophrenia generally tend to assort themselves into three different dimensions, including psychosis (“reality distortion”), negative symptoms, and disorganization. This dimensional structure is found in both treated and untreated patients, and the structure of changes during treatment are related to the dimensions of symptoms seen in untreated patients. Thus, these dimensions have considerable validity and temporal stability.

Dimensions of Cognitive Impairment in Schizophrenia

Interest in dimensions of cognitive impairment in schizophrenia was originally spurred by ideas that the impairments seen in the illness resemble those seen in illnesses with generally focal brain dysfunction. For instance, the behavioral disorganization and emotional changes seen in schizophrenia led to the idea that deficits in frontal lobe functioning were the driver of the cognitive impairments. Further, the consistent findings of impairments in working memory have also been consistent with that idea, since working memory functions appear localized to the frontal lobe in imaging studies.[1] Major disturbances in episodic memory led to the suggestion that dysfunctions in hippocampal and medial temporal lobe structures were the origin of cognitive changes seen in the illness.[2] Slowed speed of processing and reductions in reaction time are consistent with the idea of changes in basal ganglia functioning. In fact, over 15 years ago an issue of Schizophrenia Bulletin (Volume 16, 1990), guest edited by Monte Buchsbaum, was entitled “Frontal Lobes, Temporal Lobes, and Basal Ganglia: Three sites for schizophrenia?”[3]

There has been considerable discussion about whether the presence of deficits in tasks sensitive to regional brain dysfunction can actually substantiate the presence of focal brain lesions. Most contemporary thinking about the functions of cortical and subcortical structures has focused on network relationships, wherein several regions function in concert and where disruptions in any one of these linked regions can lead to deficits in tests previously shown to be sensitive to focal lesions.

A primary clinical example of such relationships is that of frontostriatal dementing conditions, such as Huntington’s disease. In this genetically transmitted illness, deterioration in the head of the caudate nucleus leads to a series of changes in cognition, behavior, and emotional functioning. One of the primary cognitive consequences of Huntington’s disease is disruption in executive functioning, as indexed by tests such as the Wisconsin Card Sorting test (WCST). This test, shown to be sensitive to anterior cortical lesions and the be associated with substantial performance deficits in people with schizophrenia, elicits substantial changes in frontal lobe regional cerebral blood flow when performed. However, in Huntington’s disease the brain changes are not in the anterior frontal lobes and these performance deficits, on a test often cited as evidence of frontal lobe dysfunction in schizophrenia, are not caused directly by frontal lobe lesions. Lesions throughout the brain can produce deficits on the WCST,[4] suggesting that cortical network failures are probably leading to performance deficits on tests of “focal” neuropsychological abilities.

The Possibility of Global Cognitive Deficits

It has been known for 50 years that people with schizophrenia often perform very poorly on most cognitive tests. This poor performance has generally been shown not to be due to poor motivation, as some cognitive tests are performed at levels consistent with premorbid functioning. It has been argued that there are “overriding deficits,” which produce reduced scores on other measures. This possibility is also consistent with the generally overlapping nature of the ability areas measured across cognitive tests. For instance, many neuropsychological tests require attention, concentration, working memory, and speeded processing for efficient performance even if they are really aimed at verbal learning and memory.

Several recent factor analytic studies have produced somewhat inconsistent results. Some of these studies have produced factor structures consistent with multiple cognitive dimensions, with separate dimensions for attention, processing speed, episodic memory, and verbal skills, while others have found a single dimension reflecting overall severity as the best fitting model. When analyses have been aimed at identification of the most informative or most important predictor of functioning, both working memory and processing speed have been implicated. This is an important finding, because test-based measures of working memory and processing speed are easily available, easy to administer, and have excellent normative standards.

Given the fact that cognitive impairments in schizophrenia likely originate from dysfunctions in cortical and subcortical networks rather than in discrete brain regions, it seems likely that the “true” answer to the dimensionality question is somewhere between a single global deficit and a multidimensional factor structure reflecting the contributions of multiple dysfunctional regions. Clinical neuropsychological tests themselves may be too overlapping in their domain coverage and thus not sensitive to specific regional deficits in any case. It may be that much less extensive assessment is required in order to see how impaired an individual patient with schizophrenia actually is.

Clinical Implications

There are several important implications for clinicians for the potential unidimensionality of cognitive impairment in schizophrenia. The most import one is efficiency of assessment. If all of the cognitive impairment in schizophrenia can be explained by performance on one or two tests, then the assessment demands for schizophrenia are markedly reduced and cognitive impairment can be estimated very easily. In the recent baseline publication of the CATIE baseline cognitive performance, the test that explained the greatest part of the total score was WAIS-III digit symbol.[5] This test takes 120 seconds to administer, has limited practice effects, and has extensive normative standards available. As a result, over 60 percent of the variance in total scores for cognitive impairment in schizophrenia can be understood in less than three minutes. This test has also been shown very recently to be the single most impaired neuropsychological measure in patients with schizophrenia.6

References

1. Callicott JH, Bertolino A, Mattay VS, et al. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cerebral Cortex 2000;10:1078–92.
2. Saykin AJ, Gur RC, Gur RE, et al. Neuropsychological function in schizophrenia: Selective impairment in memory and learning. Arch Gen Psychiatry 1991;48;618–23.
3. Buchsbaum MS. Frontal lobes, basal ganglia, temporal lobes—three sites for schizophrenia. Schiz Bull 1990;16:377–8.
4. Anderson SW, Damasio H, Jones RD, Tranel D. Wisconsin Card Sorting Test performance as a measure of frontal lobe damage. Journal of Clinical and Exp Neuropsychol 1991;13:909–22.
5. Keefe RSE, Bilder RM, Harvey PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology 2006;31:2033–46.
6. Dickinson D, Ramsey ME, Gold JM. Overlooking the obvious: A meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch Gen Psychiatry 2007;64:532–42.