In this study, we replicated our previous finding of heterogeneity in the relationship between premorbid and current IQ16
in a different group of patients with first-episode schizophrenia or schizoaffective disorder. Thus, 44% of patients showed a 10-point or greater decline in IQ, whereas the IQ of the remaining patients was stable up to the first psychotic episode, with 25% having low IQ values and the remaining patients having preserved IQ in the normal range or higher. This finding is also in agreement with other studies examining patients with established schizophrenia.15,17,18
At first episode, the preserved IQ group had less severe negative and disorganization symptoms than the other 2 groups, which were not different, but no other clinical feature distinguished the groups, including the level of premorbid social function, age at onset, duration of untreated psychosis, and severity of affective or positive psychotic symptoms.
During the 3 years following psychosis onset, there was no evidence that those with IQ deterioration continued on a declining cognitive trajectory or that those with preserved average/high IQ experienced IQ decline following onset. The low IQ group showed no statistically significant change in IQ, whereas both the DIQ and the preserved IQ groups improved. However, the rate of improvement of these 2 subgroups was no greater than that of the healthy controls, suggesting that this reflected practice effects. These findings support previous controlled studies that showed improvement in IQ following psychosis onset that was equal to or less than that of healthy controls23,24
and suggests that the improvement in IQ after the first episode seen in uncontrolled studies is nonspecific.22,25,26
To our knowledge, only 1 other study has compared estimates of premorbid IQ with IQ trajectory following psychosis onset, and this did not include healthy controls.54
In this study, patients were dichotomized according to estimated premorbid IQ; the lower premorbid IQ group showed no change in IQ when assessed both at first episode and at 6–14 years later, whereas the higher premorbid IQ group showed a decline in IQ at first episode, which subsequently improved to premorbid levels. In our study, by separating patients with and without evidence of IQ decline at first episode,18
we showed that, although patients with IQ decline improved between first psychotic episode and later follow-up, this was no greater than that seen in healthy controls. We could find no evidence that even those patients with relatively high premorbid IQ (>90) who had declined by psychosis onset subsequently improved to premorbid levels.
The same group35
also reported that IQ at psychosis onset did not predict functional outcome, whereas premorbid IQ was a significant predictor but only when adjusted for the confounding effects of DUP, gender, and age of onset. We have previously shown in a different group of first-episode patients that both premorbid IQ and IQ at first episode predicted 4-year functional outcome but that IQ at onset was the stronger predictor, and neither findings were confounded.34
In the current study, we replicated this finding in a new group of patients by examining the level of correlation between outcome measures and measures of premorbid and current IQ at baseline for the group of patients who had 3 assessments. Because premorbid and current IQ are intercorrelated, it is impossible to completely tease apart the contribution of these 2 measures; however, the results suggest that current baseline IQ was a better predictor of outcome, being more highly correlated with several cognitive measures, core negative symptoms, and occupational functioning at 3-year follow-up, as well as the length of index admission. The current study extends these findings by showing that those with preserved IQ in the average/high range had better outcomes than the other 2 groups in that they had less disorganization and negative symptoms at onset, shorter index admissions, less core negative symptoms, and better occupational outcome at 3 years. The group that showed a decline in IQ closely resembled the low IQ group in their current IQ at first episode, length of index admission, and occupational function at 3 years in addition to showing more core negative symptoms than the average/high-IQ group. Within the DIQ group, even those who declined from average/high levels had as poor an occupational outcome as those with lower premorbid IQ. These results suggest that it was not premorbid IQ but the IQ that the DIQ group arrived at by the time of the first psychotic episode that predicted a more severe illness.
These findings also have implications for the cognitive reserve hypothesis, which proposes that the higher the premorbid cognitive ability, the more resilient individuals are to the impact of cerebral dysfunction.32,33
Our findings suggest that in schizophrenia, there are some patients who benefit from cognitive reserve because they have premorbid ability in the average/high range, which remains stable following the onset of psychosis. However, there are others with similar levels of premorbid ability who undergo a decline in cognitive ability sufficient to cause diminished cognitive reserve and worse outcome. We were unable to identify any predictive measures that could distinguish these 2 groups, such as age at onset, duration of untreated psychosis, and PSA. Thus, the elucidation of factors that confer vulnerability to cognitive change during the development of psychosis requires further study because this group may be particularly amenable to intervention if detected early enough.
The current findings and those of others21
have failed to elucidate possible cognitive correlates of the continuing reductions in gray matter volume following psychosis onset seen in neuroimaging studies.19,20
Gray matter volume loss early in the illness is clearly of clinical relevance because Cahn et al55
found that those with the greatest volume loss over the first year had the highest negative symptoms and poorest functional outcome. One explanation is that the structural changes giving rise to cognitive impairment have occurred by the time of presentation with psychosis, and therefore, the neural context for poor outcome is already established for some patients at this stage. Although the continuing volumetric reductions detected on MRI could represent the manifestation of these changes, their functional consequences may already have been declared. Our data support the view that the ability to detect patients with a deteriorating cognitive course very early in the development of psychosis, at the ultra high-risk stage, will be important for neuroprotective strategies in schizophrenia.56–58
At baseline, the low IQ and DIQ groups performed equivalently on tests of verbal learning and memory, working memory, and planning and significantly worse than the controls and preserved IQ groups. These findings are compatible with those of Kremen et al17
who found that subgroups of schizophrenia patients with preserved IQ and DIQ, matched on current IQ, demonstrated similar neuropsychological performance. Our DIQ group had comparable current IQ to our low IQ group, and because performance on all cognitive measure was the same in these 2 patient groups, our findings support their conclusion that in schizophrenia; current neuropsychological performance is a function of current IQ rather than prior intellectual trajectory.
At follow-up, there was evidence of improvement over time on verbal immediate memory and learning and spatial working memory span, but this was equivalent across IQ subgroups and controls. Improvement in the controls indicated that practice enhanced performance, and this finding emphasizes the importance of a comparison control group when assessing change in performance of specific cognitive functions over time in keeping with a study of improvement in cognition following treatment with antipsychotic medication.29
Despite performing better than the low IQ and DIQ groups, those with preserved IQ were significantly impaired compared with controls on verbal learning and spatial working memory manipulation. We and others have previously found that preserved IQ subgroups have impaired executive function and verbal memory.16–18,59
However, when IQ and specific measures of memory and executive function were compared as predictors of outcome, we previously found that only IQ consistently predicted functional outcome whether measured as a premorbid estimate or at 3 time points over 4 years following onset.34
A limitation of this study is the use of an indirect measure of premorbid IQ. There are many studies substantiating the use of tests of irregular word pronunciation in normal volunteers and in a variety of neuropsychiatric disorders.60–63
The majority of studies comparing patients with chronic stable or acutely symptomatic schizophrenia with matched controls and other patient groups have found these tests to be a valid measure of premorbid IQ,64,65
and other studies have found estimated IQ to be stable over time.66,67
Nevertheless, the use of tests of irregular word pronunciation in schizophrenia has been criticized on the grounds that the disorder itself may be related to impairment in verbal ability, thus causing IQ to be underestimated.68
Against this are studies that have found that current vocabulary approximates direct measures of premorbid IQ in schizophrenia.69,70
Conversely, another criticism is that irregular word-reading tasks overestimate IQ at the lower FSIQ range, giving a spurious impression of IQ decline.70
We do not think that this explains our findings because 25% of patients were classified as having low current IQ, characterized as equivalent estimated premorbid and current IQ. Another limitation is that, although we completed all assessments for 60 patients when these were divided into IQ groups, the numbers were inevitably rather small. Our findings therefore require further study in larger high-risk groups where direct measures of premorbid IQ can be ascertained.