It is important to know how specific the cognitive dysfunction in schizophrenia is, particularly relative to affective disorders, which frequently present with psychosis and may resemble schizophrenia clinically. Contrasts in the severity and pattern of cognitive impairment between patients with schizophrenia and those with affective disorders (unipolar and bipolar) have been studied in adults, but not in children and adolescents. Many studies have found that patients with schizophrenia are more cognitively impaired than patients with affective disorders.49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69
However, some studies have shown no or relatively limited cognitive differences between these diagnostic groups.70,71,72,73,74,75,76,77,78,79,80,81,82
in his review of the neurocognitive differences between schizophrenia and affective disorders (mainly bipolar disorder), concludes that the literature, on balance, provides support for the view that patients with bipolar disorder suffer less severe cognitive impairments than do patients with schizophrenia. In general, studies that did find differences in cognitive performance between patients with schizophrenia and those with affective disorder found the schizophrenia group to be more impaired relative to the affective group in global intelligence (IQ) and/or some or all of the domains of attention, memory and executive functioning.53,60,62,65,67
This seems to suggest a profile or pattern of cognitive impairment specific to schizophrenia relative to affective disorders. When healthy controls were included in studies, the affective group's cognitive performance was generally found to be intermediate between the group with schizophrenia and the healthy controls. This was a consistent trend even in those studies where the differences between the groups did not reach statistical significance.79,84
notes that, whereas some studies had found the groups to be equivalent in impairment, no studies had found patients with bipolar disorder to be consistently more impaired than patients with schizophrenia.
On a cautionary note, as highlighted in the meta-analysis by Heinrichs and Zakzanis,9
the question of whether the cognitive deficits in schizophrenia are generalized or specific may not yet have been definitively resolved in the literature. One cannot necessarily conclude that the deficits found in studies are qualitative rather than quantitative. Differences in difficulty and complexity levels and other psychometric properties of the neuropsychologic tests make it difficult to draw firm conclusions, and it is possible that certain abilities, or tests for these abilities, may be more sensitive to global nonspecific deficits than are others.62
It should be noted as well that most of the studies were selective rather than comprehensive in the cognitive domains tested. Statistical issues such as lack of power due to inadequate sample size may also account for some differences in findings. Goldberg and Gold,4,83
while arguing in favour of differences in cognitive profile between the diagnostic groups, note that there is less consistent support in the literature for such qualitative differences than for quantitative differences.
If the deficits are mainly quantitative, one cannot definitively rule out the possibility that the cognitive differences merely reflect differences in severity of illness. The different diagnostic groups could perhaps be most similar cognitively when acutely psychotic, thus demonstrating a general effect of psychosis, rather than a specific effect of diagnosis (i.e., state rather than trait), on cognitive functioning.67,85
For example, Hoff et al71
and Albus et al77
did not find a significant difference in cognitive function between acutely ill patients with affective disorder and those with schizophrenia.
Furthermore, the subjects with affective disorder included in some studies did not necessarily have a history of any psychotic symptoms at all. Jeste et al86
argue that this is a relevant factor, because they found a difference between psychotic and nonpsychotic affective disorders, with the patients with psychotic affective disorder, about half of whom were psychotic at the time of the assessment, resembling the patients with schizophrenia with respect to cognitive profile. Jeste's group also found a similar cognitive profile for schizoaffective disorder and schizophrenia,87
as did Townsend et al.88
Jeste and colleagues argue that the neuropsychologic deficits may extend to the full spectrum of psychotic illness, including affective psychosis, rather than being specific to schizophrenia.87
On the other hand, in support of the specificity argument proposed by Elvevag and Goldberg,8,83
other recent studies have provided further evidence that the deficits are specific to schizophrenia relative to psychotic affective disorders and that they are not dependent on the presence or severity of psychosis: Mojtabai et al,62
in a large study, found consistent differences between schizophrenia and psychotic affective disorders (both bipolar and unipolar). Although the subjects with schizophrenia in this study were on average more psychotic than the subjects with affective disorder at the time of testing, the pattern of significant findings was the same when only the data for the subjects with no current psychotic symptoms were analyzed.62
Seidman et al67
found that patients with schizophrenia had more severe cognitive impairment than patients with chronic psychotic bipolar disorder, although they did have similar cognitive profile patterns. The differences were maintained even when IQ was controlled for, which was significantly lower in the schizophrenia group. Virtually all subjects in that study had low-to-moderate levels of psychosis at the time of testing.67
The argument for cognitive impairment being more the result of psychosis than of schizophrenia is also difficult to reconcile with the fact that severity of positive symptoms has generally been found in most studies to be unrelated to cognitive performance8,85
and with the stability of the deficits over time described earlier.
There are other clinical factors that could perhaps account for the discrepant results of studies, aside from the severity of psychosis. A very acute affective state (versus trait) at the time of testing, namely, severe depression or mania, can probably be expected to affect cognitive performance. Severity of affective symptoms is not generally comparable across studies, so one cannot quantify the impact of this variable. Diagnostic uncertainty (discussed later in this paper) is another factor that may contribute to inconsistent results.
Comorbid borderline intellectual functioning, mental retardation and learning disorders would impair cognitive test performance and are, therefore, generally exclusion criteria for most studies. However, the frequent co-occurrence of these cognitive limitations may indeed be integral to the neurodevelopmental basis of schizophrenia, that is, they may in fact be part of the pathology of schizophrenia, particularly early onset schizophrenia. Thus, for example, the study cited earlier by Kumra et al,18
which compared cognitive deficits in childhood-onset schizophrenia and atypical psychosis, excluded patients with an IQ below 70. A large proportion of their potential subjects (39% of 44 patients with childhood-onset schizophrenia) were excluded from the study based on this criterion. Even within the normal range of IQ, researchers need to be careful not to overcorrect for differences in general intellectual functioning by matching subjects with affective disorder or healthy controls to the subjects with schizophrenia based on IQ or educational attainment, as Seidman et al point out.67
In their study, they avoided this pitfall by adjusting for parental socioeconomic status instead.
It should be noted that most studies do not control for medication effects, which is a complex and difficult task. Antipsychotics and other psychotropic medications may have variable effects on cognition. Some antipsychotics, particularly the novel or atypical antipsychotics, are said to partially improve aspects of cognition,89,90,91
but the different cognitive measures used across studies make it hard to draw definitive conclusions about the beneficial effects of antipsychotics, and some putative positive results may really be method artifacts.92,93
Many antipsychotics may in fact have a detrimental effect on cognition because of their sedating and anticholinergic properties. Motor (extrapyramidal) side effects of antipsychotics may also affect psychomotor speed, which could affect performance on some cognitive tests. Many patients studied are also on mood stabilizers, most of which are known to impair aspects of cognition, as is the case with anti-parkinsonian drugs, benzodiazepines and some antidepressants.
In summary, the literature on balance does appear to support a conclusion that the deficits are more severe in schizophrenia compared with affective disorder, and that there may be some degree of specificity to schizophrenia in the pattern of deficits. The deficits do not appear to be merely associated with the level of psychotic symptoms, though they should probably be expected to be transiently worsened when the psychotic (or affective) state is very acute and profound. Cognition may be affected by several clinical and treatment variables.