Neurocognitive functioning in patients with first-episode schizophrenia : Results of a prospective 5-year follow-up study
Albus M, Hubmann W, Mohr F, Hecht S, Hinterberger-Weber P, Seitz NN, et al.;
Commented by , 26 Oct 2006
Aim of the study
Cognitive dysfunction is a serious problem in schizophrenia and is by some authors considered a key component of the disorder. Previous studies have shown that cognitive dysfunction is present already in first episode schizophrenia. However, long-term follow-up studies that included a group of normal controls are scarce. In this context the authors conducted a prospective 5 year follow-up study of patients with a first episode of schizophrenia and matched controls.
Method
The participants were 71 first episode patients who were treated in a typical German district hospital in Munich. These patients were compared with 71 age, gender, education and socio-economic status matched healthy controls. Neurocognitive functioning was assessed at baseline (i.e. in the weeks after the admission for the first episode), at 2-years and at 5-years follow-up.
A number of tests were summarized to provide information on the following cognitive domains: verbal intelligence (VBI), verbal fluency (VBF), verbal learning (VBL), spatial organisation (SPT), semantic memory (SEM), visual memory (VIM), delay/retention rate (DEL), short-term memory (STM), visuomotor processing and attention (VSM) and abstraction/flexibility (ABS).
To provide a comparable measure for all domains the results were converted into z-scores. There were four main questions:
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how does the cognitive function of people with a first episode schizophrenia compare over time to that of normal controls?
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what is the course over time of cognitive deficits in such patients?
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how do cognitive symptoms relate to positive and negative symptoms?
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are there differences between no treatment, atypical and typical antipsychotics?
Results
The main results of the numerous outcomes reported were:
Ad 1
People with a first episode of schizophrenia did worse than normal controls in almost all cognitive domains and at all follow-ups (baseline, year 2, year 5).
Ad 2
Cognitive function remained altered, although there were certain improvements in both groups over time.
Ad 3
Cognitive dysfunction was more related to negative symptoms than to positive symptoms.
Ad 4
In only a few domains those not on antipsychotic medication at five year follow-up did better than treated patients. There were no significant differences between typical and atypical antipsychotics in this regard. An important confounder was, however, lower premorbid education which predicted cognitive dysfunction.
Dr Leucht's comments
The most important finding may be that cognitive dysfunction in schizophrenia remains relatively stable over the first 5 years rather than showing a rapid decline. In a way this underlines the need for optimised and continued treatment to avoid chronification of the disease. The fact that in some areas there was even an improvement over time may either reflect effects of continuing improvement the longer a patient is symptom free or training effects.
Since many participants in the cohort relapsed and since improvement was even seen among normal controls, the latter assumption appears more likely. That cognitive dysfunction is associated more strongly with negative symptoms than with positive symptoms is a relatively robust finding across studies. From a clinical perspective it seems, however, not surprising that low levels of positive symptoms as was the case here do not interfere much with cognition.
Results might differ in highly psychotic patients who are probably not even able to take part in cognitive testing. Those 15 participants who were not taking medication at 5 year follow up did better on some cognitive domains. It is well possible that this finding does not reflect deleterious effects of medication, but rather that those who did not receive medication also did clinically better so that antipsychotics were discontinued.
Finally, the study did not show a difference between the use of atypical antipsychotics compared to conventional antipsychotics in terms of cognitive functioning. Although a superiority of the atypical antipsychotics had been found in recent meta-analyses, the difference was small. Therefore, the current study may reflect the difficulty to transfer the results of efficacy studies to effectiveness studies (the so-called "efficacy versus effectiveness gap"). As the authors state in their last sentence, how much cognitive dysfunction impairs patients real life functioning still remains to be determined.