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Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins.

ABSTRACT: Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

SUBMITTER: Nishimura Y

PROVIDER: S-EPMC5109992 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge.To investigate the contributions of glutamate and ?-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia.Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015.Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance.The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F?=?4.39, P?=?.04) and glutamate (F?=?9.69, P?=?.002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P?=?.008), lower glutamate level (P?=?.05), and higher ratio of glutamine to glutamate (P?=?.003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P?=?.002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P?=?.38 [root-mean-square error of approximation, P?<?.001] by ?2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia.The role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated. These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia.

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Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins.

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