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Antipsychotic Medications: Linking Receptor Antagonism to Neuropsychological Functioning in First Episode Psychosis

Published online by Cambridge University Press:  04 April 2012

Heather A. Baitz
Department of Psychology, Simon Fraser University, Burnaby, British Columbia
Allen E. Thornton*
Department of Psychology, Simon Fraser University, Burnaby, British Columbia
Ric M. Procyshyn
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
Geoffrey N. Smith
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
G. William MacEwan
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
Lili C. Kopala
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
Alasdair M. Barr
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia
Donna J. Lang
Department of Radiology, University of British Columbia, Vancouver, British Columbia
William G. Honer
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
Correspondence and reprint requests to: Allen E Thornton, Department of Psychology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada. E-mail:


Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D2 antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D2 receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D2 load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices. (JINS, 2012, 18, 1–11)

Research Articles
Copyright © The International Neuropsychological Society 2012

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