Attenuated Mismatch Negativity in Attenuated Psychosis Syndrome Predicts Psychosis: Can Galantamine-Memantine Combination Prevent Psychosis?

Although first proposed in 1987, early diagnosis and intervention of psychotic disorders has only recently become a priority in the field. The interest in clinical high risk (CHR) for psychosis skyrocketed after attenuated psychosis syndrome (APS) was added to the DSM-5. There is evidence that in individuals with APS, attenuated mismatch negativity (MMN: functioning of the auditory sensory memory system) is a robust biomarker that can predict transition to psychosis. The underlying pathophysiological mechanism of MMN is via the interaction of N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α-7nACh) receptors. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α-7nACh receptors. Memantine is an NMDA receptor antagonist. Memantine has been shown to enhance MMN in people with schizophrenia. Although no studies with galantamine have measured MMN, encenicline, an α-7 nicotinic partial agonist, increased MMN in people with schizophrenia. MMN has been suggested as a potential biomarker with the galantamine-memantine combination for the treatment of neuropsychiatric disorders. Hence, the galantamine-memantine combination may enhance MMN, thereby preventing CHR to psychosis. With no treatments available, randomized controlled trials are warranted with the galantamine-memantine combination to delay or prevent conversion to psychosis in individuals with CHR.