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

• Published in: Clinical neurophysiology Vol. 166; pp. 142 - 151
• Main Authors: Storozheva, Zinaida I., Kirenskaya, Anna V., Samylkin, Denis V., Gruden, Marina A., Sewell, Robert D.E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: Adult; Cognition - physiology; Electroencephalography; Event-related potentials P300; Event-Related Potentials, P300 - genetics; Event-Related Potentials, P300 - physiology; Evoked Potentials, Auditory - genetics; Evoked Potentials, Auditory - physiology; Female; GAD1 rs3749034 polymorphism; Glutamate Decarboxylase - genetics; Humans; Male; Middle Aged; Neurology; Oddball paradigm; Polymorphism, Single Nucleotide - genetics; Schizophrenia; Schizophrenia - genetics; Schizophrenia - physiopathology; Young Adult; GAD1 rs3749034 polymorphism; Schizophrenia; Oddball paradigm; Event-related potentials P300; event-related potentials P300; schizophrenia; oddball paradigm
• ISSN: 1388-2457; 1872-8952; 1872-8952
• DOI: 10.1016/j.clinph.2024.08.001

[Display omitted] •An increased frequency of the cytosine-cytosine allele in GAD1 rs3749034 polymorphism was found in schizophrenic patients.•A decreased patient oddball task performance was found only in the cohort of cytosine-thymine carriers between study groups.•A higher P300 amplitude and shorter latency in cytosine-cytosine versus cytosine-thymine carriers was observed for both groups. 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. 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). 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. 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. These results are important for understanding underlying mechanisms and the development of evidence-based methods for assessing the risk of schizophrenia.