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Gluatamate level may influence auditory mismatch negativity, verbal working memory in schizophrenia

Recent findings show a significant association between in vivo glutamatergic measurements, auditory mismatch negativity and verbal working memory in schizophrenia.

“Auditory mismatch negativity 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 [auditory mismatch negativity] has not been directly examined in patients with schizophrenia, to our knowledge,” Laura M. Rowland, PhD, of the University of Maryland School of Medicine, Baltimore, and colleagues wrote.

To assess the effects of glutamate and γ-aminobutyric acid on auditory mismatch negativity and digit sequencing task performance in schizophrenia, researchers evaluated 53 healthy controls and 45 individuals with schizophrenia. Study participants completed an electroencephalographic session for mismatch negativity, magnetic resonance spectroscopy for glutamate and γ-aminobutyric acid and a digit sequencing task. Study participants had an approximate mean age of 37 years.

Individuals with schizophrenia had a mean illness duration of 14.7 years.

Mismatch negativity amplitude (P = .04) and glutamate (P = .002) were reduced among individuals with schizophrenia.

Smaller auditory mismatch negativity amplitude was significantly associated with lower γ-aminobutyric acid level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003).

Decreased auditory mismatch negativity was associated with poor verbal working memory in schizophrenia (P = .002).

Modeling indicated a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to auditory mismatch negativity to verbal working memory, according to researchers.

“The modeling supports the contention that [auditory mismatch negativity] may index the glutamatergic contribution to verbal working memory performance in schizophrenia. γ-Aminobutyric acid level was also involved but appeared to be more modest and indirect,” the researchers wrote. “These data provide strong support for the involvement of the glutamatergic system in [auditory mismatch negativity] and verbal working memory function in schizophrenia.” – by Amanda Oldt

Disclosure: Rowland reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.