Association of GAD1 gene polymorphism rs3749034 with the information processing and cognitive event-related potentials in schizophrenia patients and healthy subjects

Storozheva, Zinaida I., Kirenskaya, Anna V., Samylkin, Denis V., Gruden, Marina A. and Sewell, Robert D.E. 2024. Association of GAD1 gene polymorphism rs3749034 with the information processing and cognitive event-related potentials in schizophrenia patients and healthy subjects. Clinical Neurophysiology 166 , pp. 142-151. 10.1016/j.clinph.2024.08.001 Item availability restricted.

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Abstract

Objective Glutamic acid decarboxylase, an enzyme in GABA biosynthesis, is encoded by the GAD1 gene, the transcriptional activity of which is affected by the rs3749034 polymorphism. The aim was to investigate the effects of rs3749034 on cognitive event-related potentials (P300) in healthy subjects and schizophrenic patients. Methods Determination of rs3749034 polymorphism was performed in 89 healthy volunteers and 109 schizophrenic patients (males). Two-stimulus oddball task performance and P300 auditory evoked potentials were analyzed and patient symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results An increased frequency of C allele carriers was disclosed in patients. In controls, superior task performance was observed in cytosine-thymine carriers, while a greater P300 amplitude and shorter latency were found in C/C carriers. Analogous effects were found in patients with a disease onset before 25 years of age. Higher N5 and lower P3 and G5 PANSS scales were revealed in C/C homozygotes. Conclusions The findings substantiate an involvement of GABA-ergic mechanisms in maintaining an optimal excitatory-inhibitory balance and an association of rs3749034 with early-onset disorder and negative symptoms of schizophrenia. Significance These results are important for understanding underlying mechanisms and the development of evidence-based methods for assessing the risk of schizophrenia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Publisher:	Elsevier
ISSN:	1388-2457
Date of First Compliant Deposit:	22 October 2024
Date of Acceptance:	6 August 2024
Last Modified:	07 Nov 2024 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/173237

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