A longitudinal investigation into the influence of atypical antipsychotics on cognitive function in schizophrenia

Tyson, Philip John

January 2003

Thesis or dissertation

© 2003 Philip John Tyson. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Cognitive deficits are a well recognised feature of schizophrenia, with patients showing disproportionate impairments in aspects of memory and executive function. Atypical antipsychotics have shown some success at remediating these deficits which suggests that the basis of the cognitive impairment might be neurochemical in origin. However, the precise nature of this effect is unknown. Mechanisms of action might involve antagonism of 5 HT-2A receptors which results in increased prefrontal dopamine, or the affinity of these medications to dopamine receptors or multiple receptors.

Patients with a diagnosis of schizophrenia were recruited for the study within 6 weeks of starting one of the atypical antipsychotics; clozapine, olanzapine, risperidone, quetiapine & amisulpride. They were assessed on clinical variables and a wide battery of cognitive tests at baseline, 9-month-follow-up and 18-month-follow-up. For the analysis the whole group was split into different subgroups according to the neurochemical properties of the individual antipsychotics;

• Those with a high affinity for 5HT-2A receptors (risperidone, olanzapine & c1ozapine) vs. those with a low affinity for these receptors (quetiapine & amisutpride).
• Those with a preferential affinity for dopamine receptors (risperidone & amisulpride) vs.those with an affinity for multiple receptors (otanzapine, clozapine & quetiapine).
• Those with a fast dissociation from the 02 receptor (c1ozapine, quetiapine & amisulpride) vs. those with a slower dissociation from this receptor (olanzapine & risperidone)
• In addition the individual medication groups were compared on all measures

The main findings were that medications that had a high affinity for 5-HT2A receptors exerted negative effects on some aspects of cognition, whilst those with a low affinity for 5HT-2A receptors exerted beneficial effects. In addition, the individual atypical antipsychotics differed in their cognitive effects. It is concluded that affinity to 5HT-2A receptors is an important determinant of the cognitive response to atypical antipsychotics.

Postgraduate Medical Institute, The University of Hull
Mortimer, Ann, 1957-
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