Dexamphetamine selectively increases 40 Hz auditory steady state response power to target and nontarget stimuli in healthy humans

Dexamphetamine selectively increases 40 Hz auditory steady state response power to target and nontarget stimuli in healthy humans

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J Psychiatry Neurosci 2013; 38(1):24-32

Matthew A. Albrecht, PhD; Greg Price, PhD; Joseph Lee, MBBS; Rajan Iyyalol, MBBS, MD, DPM; Mathew T. Martin-Iverson, PhD

Albrecht, Martin-Iverson — Pharmacology and Anaesthesiology Unit, School of Medicine and Pharmacology, The University of Western Australia; Albrecht, Price, Martin-Iverson — Centre for Clinical Research in Neuropsychiatry, The University of Western Australia and Graylands Hospital; Price, Lee, Martin-Iverson — Statewide Neurophysiology Department, Graylands Hospital; Price, Lee — School of Psychiatry and Clinical Neurosciences, The University of Western Australia; Lee, Iyyalol — Graylands Hospital, Mt. Claremont, Perth, Australia

Abstract

Background: An emerging endophenotype of schizophrenia is the reduction of both power and phase locking of the 40 Hz auditory steady state response (ASSR), and there have been a number of reports linking increased γ activity with positive psychotic symptoms. Schizophrenia and, more specifically, positive psychotic symptoms have been closely linked to increased dopamine (DA) neurophysiology. Therefore, we gave dexamphetamine to healthy participants to determine the effect that increased DA transmission would have on the ASSR.

Methods: We administered 0.45 mg/kg of dexamphetamine orally in a double-blind placebo-controlled crossover study. Stimuli were 20 Hz and 40 Hz click trains presented in an auditory oddball-type stimulus format (probability of stimulus presentation: 0.2 for targets, 0.8 for nontargets).

Results: We included 44 healthy volunteers (18 women) in the study. Dexamphetamine significantly increased the 40 Hz power for both target and nontarget ASSR stimuli. Dexamphetamine did not significantly affect the 40 Hz phase-locking factor (PLF) or the 20 Hz power and PLF. Whereas there were significant effects of selective attention on power and PLF for 20 and 40 Hz ASSR, there were no significant interactions between dexamphetamine and selective attention.

Limitations: Dexamphetamine releases both noradrenaline and DA with equal potency. Further research with selective dopaminergic and noradrenergic agents will better characterize the effects of monoamines on γ activity.

Conclusion: The results demonstrate a frequency-specific effect of dexamphetamine on the ASSR. This finding is consistent with previous research that has found an association between increased γ and positive symptoms of psychosis. However, this result also raises the possibility that previous 40 Hz ASSR findings in people with schizophrenia may be confounded by effects of antipsychotic medication. Possible neural mechanisms by which dexamphetamine specifically increases 40 Hz power are also discussed.

Australian and New Zealand Clinical Trials Registry number: ACTRN12608000610336.


Submitted Oct. 11, 2011; Revised Mar. 3, Apr. 11, 2012; Accepted Apr. 19, 2012.

Acknowledgements: M.A. Albrecht is the recipient of a Clinical Neurophysiology supplementary scholarship from the Department of Neurophysiology, North Metropolitan Area Health Service — Mental Health and the School of Medicine and Pharmacology of the University of Western Australia. This research was funded by a National Health and Medical Research Council grant (ID: 254619) awarded to M.T. Martin-Iverson.

Competing interests: As above for M.A. Albrecht and M.T. Martin-Iverson. None declared for G. Price, J. Lee and R. Iyyalol.

Contributors: All authors helped design the article, acquired the data, reviewed the article and approved its publication. M.A. Albrecht, G. Price and M.T. Martin-Iverson analyzed the data. M.A. Albrecht and M.T. Martin-Iverson wrote the article.

DOI: 10.1503/jpn.110145

Correspondence to: M.A. Albrecht, Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, Private Bag No. 1, Claremont WA, 6910, Australia; albrem04@student.uwa.edu.au