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Amphetamine effects on MATRICS Consensus Cognitive Battery performance in healthy adults

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Abstract

Background

Cognitive deficits contribute strongly to functional disability in schizophrenia. The cost of identifying and testing candidate procognitive agents is substantial. Conceivably, candidate drugs might be first identified by positive effects on cognitive domains in sensitive subgroups of healthy subjects. Here, we examined whether the MATRICS Consensus Cognitive Battery (MCCB) detected procognitive drug effects in subgroups of healthy individuals.

Methods

The effects of 20 mg amphetamine (AMPH) on MCCB performance were tested in a double-blind, placebo-controlled crossover study of 60 healthy adults. AMPH effects were compared in subgroups of subjects characterized by low vs. high placebo MCCB scores, and by extreme values on personality subscales associated with schizophrenia-relevant biomarkers.

Results

AMPH produced autonomic and subjective effects, but did not significantly change MCCB composite scores or individual domain scores across the inclusive sample of 60 subjects. AMPH-induced MCCB changes were significantly (inversely) related to placebo MCCB performance: among individuals with lower placebo scores, AMPH enhanced performance; while among individuals with higher placebo scores, it impaired performance. A potential impact of regression to the mean was assessed and could not be ruled out. Both placebo MCCB performance and AMPH effects on MCCB scores were significantly related to personality domains associated with schizophrenia-linked genetic- and/or neurophysiological substrates.

Conclusions

Among healthy adults, AMPH effects on MCCB performance were detected only among specific subgroups, and in specific cognitive domains. Strategies that utilize drug-induced changes in MCCB performance in healthy subjects to screen for candidate procognitive drugs should consider the use of “enriched” subgroups with specific neurocognitive or personality characteristics.

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Acknowledgments

NRS is supported by R01-MH059803, R34-MH093453, R01-MH094320 and the VISN22 Mental Illness Research, Education & Clinical Center (MIRECC); HHC is supported by T32-MH018399 and the APF/Merck Early Academic Career Award. Outstanding administrative support was provided by Ms. Maria Bongiovanni. Excellent technical support was provided by Mr. Justin Kei.

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  1. Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA

    Hsun-Hua Chou, Jo A. Talledo, Sarah N. Lamb, Wesley K. Thompson & Neal R. Swerdlow

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  1. Hsun-Hua Chou
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  2. Jo A. Talledo
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  3. Sarah N. Lamb
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Correspondence to Neal R. Swerdlow.

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Supplemental Fig 1

Autonomic measures after MCCB completion. HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure. Asterisk indicates significant main effect of drug (AMPH > PBO). (PDF 64.3 kb)

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Chou, HH., Talledo, J.A., Lamb, S.N. et al. Amphetamine effects on MATRICS Consensus Cognitive Battery performance in healthy adults. Psychopharmacology 227, 165–176 (2013). https://doi.org/10.1007/s00213-012-2948-x

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