Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.74835
Keywords
mismatch negativity; acetylcholine; dopamine; NMDA receptor; schizophrenia; volatility; Human
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The study aimed to test whether auditory mismatch responses are sensitive to the enhancing and diminishing effects of cholinergic and dopaminergic function, and found differential effects of drugs on mismatch responses, which may be useful for predicting treatment responses in schizophrenia.
The auditory mismatch negativity (MMN) has been proposed as a biomarker of NMDA receptor (NMDAR) dysfunction in schizophrenia. Such dysfunction may be caused by aberrant interactions of different neuromodulators with NMDARs, which could explain clinical heterogeneity among patients. In two studies (N = 81 each), we used a double-blind placebo-controlled between-subject design to systematically test whether auditory mismatch responses under varying levels of environmental stability are sensitive to diminishing and enhancing cholinergic vs. dopaminergic function. We found a significant drug x mismatch interaction: while the muscarinic acetylcholine receptor antagonist biperiden delayed and topographically shifted mismatch responses, particularly during high stability, this effect could not be detected for amisulpride, a dopamine D2/D3 receptor antagonist. Neither galantamine nor levodopa, which elevate acetylcholine and dopamine levels, respectively, exerted significant effects on MMN. This differential MMN sensitivity to muscarinic versus dopaminergic receptor function may prove useful for developing tests that predict individual treatment responses in schizophrenia.
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