Elsevier

Schizophrenia Research

Volume 53, Issue 3, 15 January 2002, Pages 229-238
Schizophrenia Research

Neuropsychological impairments in neuroleptic-responder vs. -nonresponder schizophrenic patients and healthy volunteers

https://doi.org/10.1016/S0920-9964(01)00279-1Get rights and content

Abstract

To determine whether two groups of schizophrenic patients representing the two extremes of the neuroleptic response-spectrum (consistent responders vs. consistent nonresponders) differ with respect to their neuropsychological profile. Neuroleptic-responder (R; n=36) and -nonresponder (NR; n=39) schizophrenic patients were recruited according to a priori defined criteria of responsiveness to typical neuroleptics. Seven neuropsychological domains were assessed and compared between groups: attention-vigilance, abstraction-flexibility, spatial organization, visual-motor processing, visual memory, verbal abilities, and verbal memory and learning. All measures were standardized using the scores of 36 healthy volunteers. NR schizophrenic patients performed worse in all neuropsychological domains compared to normal controls and R schizophrenic patients. However, only performances on visual memory, verbal abilities, and verbal memory and learning were significantly poorer in NR compared to R patients. Only the latter domain significantly differentiated NR patients from the other two groups. R patients performed at an intermediate level in all domains. This report of differences in neuropsychological profile between neuroleptic-responder and -nonresponder schizophrenic patients adds to the growing evidence supporting the value of distinguishing schizophrenic patients on the basis of their therapeutic response to neuroleptics.

Introduction

Though most schizophrenic patients improve with neuroleptic treatment, a substantial proportion (15–25%) remains severely symptomatic in spite of adequate pharmacotherapy (Brenner et al., 1990). Response to neuroleptics in the same subject tends to be similar from one episode to the other, suggesting ‘trait’ properties (Garver et al., 1988). Pharmacokinetic or pharmacodynamic factors are generally thought to play a minimal role, if any, in the variability of response to neuroleptics (Wolkin et al., 1989). Clinical predictors/correlates of favorable response to neuroleptic drugs include female gender (Meltzer et al., 1997), later age at onset (van Kammen et al., 1996), blink-rate decrease under haloperidol challenge (Karson et al., 1982) and rare spontaneous movement disorders prior to neuroleptic use (Chatterjee et al., 1995). Several studies reported that high pre-treatment plasma levels of homovanillic acid predict good response to neuroleptics (Mazure et al., 1991, Davidson et al., 1991), suggesting that disturbances in dopamine neurotransmission may be more specific to neuroleptic-responder schizophrenic patients. Differences between neuroleptic-responder and -nonresponder patients in brain morphology (Zipursky et al., 1998) and metabolism (Bartlett et al., 1998) have also been reported. Preliminary evidence from genetic epidemiological studies indicate that the relatives of neuroleptic-nonresponder patients show an increased prevalence of schizophrenia spectrum disorders compared to relatives of -responder patients (Silverman et al., 1987). These and other (Itil et al., 1975, Czobor and Volavka, 1992, Mohr et al., 1998) characteristics support the hypothesis that neuroleptic-responder and -nonresponder schizophrenic patients may represent distinct, though possibly overlapping, phenotypes of schizophrenia (Brenner et al., 1990, Brown, 1995).

Neuropsychological deficits have been consistently reported in schizophrenic patients (Levin et al., 1989) and, to a lesser extent, in their non-schizophrenic first-degree relatives (Kremen et al., 1994). However, there is a wide range of variability in the severity and the nature of neuropsychological domains reported to be deficient in schizophrenia. While many studies have found a relatively non-specific profile of neuropsychological deficits (Mohamed et al., 1999), other studies reported deficits mainly in domains served by the dorsolateral prefrontal and medial temporal cortices.

Clinically, neuropsychological deficits have been found to be more pronounced in patients having poor functional outcome (also called Kraepelinian schizophrenia) (Zec 1995) and those who do not respond to neuroleptic medication (Harvey et al., 1991). It is therefore possible that poor response to neuroleptic drugs and cognitive deficits represent two traits shared by of a specific subgroup of schizophrenic patients. In the present study, we propose to assess and compare neuropsychological functioning in schizophrenic patients selected on the basis of their long-term therapeutic response to typical neuroleptics. We hypothesized that: (1) neuroleptic non-responder patients have poorer overall neuropsychological performance compared to responder patients, and (2) that the profile of deficits in non-responder schizophrenic patients is more pronounced in some domains of neuropsychological functioning reflecting more specific abnormalities in either one of the major cortical foci believed to mediate the pathogenesis of schizophrenia. To test these hypotheses, we compared performances in attention-vigilance, abstraction-flexibility, spatial organization, visual-motor processing, visual memory, verbal memory and learning and verbal abilities between schizophrenic patients ascertained according to their long-term responsiveness to conventional neuroleptics.

Section snippets

Subjects

Assignment of patients to responder or non-responder groups was done in two steps. First, we identified potential candidates based on their previous history of poor therapeutic response (schizophrenic patients treated with or considered by their psychiatrist as candidates for treatment with atypical neuroleptics because of resistance to typical neuroleptics) or very good response to typical neuroleptics (based on the clinical impression of their treating physicians and/or nurse). Three

Results

The two patient groups were not significantly different with respect to age, level of education, SES of the head of the household, length of follow-up at their respective hospital prior to enrolment, and mini-mental state examination (MMSE) scores (see Table 1). The NR group included more males (p=0.03) and more patients with non-paranoid schizophrenia (p=0.02) than the R group. As expected, the BPRS, SANS, SAPS, Neuroleptic response scores as well as the percentage of time spent as an

Discussion

In the present study, schizophrenic patients selected on the basis of long-term poor response to conventional neuroleptics were found to have significant and robust deficits in verbal memory and learning compared to schizophrenic patients who show excellent response to neuroleptics. Differences in visual memory and verbal abilities between the two groups of patients were also present but did not discriminate between them. These results suggest that verbal memory, a neuropsychological function

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