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Genetic polymorphisms in COMT and BDNF influence synchronization dynamics of human neuronal oscillations.

ABSTRACT: Neuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. We hypothesized that this variability could be partially explained by genetic polymorphisms in neuromodulatory genes. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in catechol-O-methyltransferase (COMT) Val¹⁵⁸Met and brain-derived neurotrophic factor (BDNF) Val⁶⁶Met. Both COMT and BDNF polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only BDNF polymorphism affected the strength of large-scale synchronization. Our findings demonstrate that COMT and BDNF genetic polymorphisms contribute to inter-individual variability in neuronal oscillation dynamics. Comparison of these results to computational modeling of near-critical synchronization dynamics further suggested that COMT and BDNF polymorphisms influenced local oscillations by modulating the excitation-inhibition balance according to the brain criticality framework.

SUBMITTER: Simola J

PROVIDER: S-EPMC9460523 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in <i>COMT</i> and <i>BDNF</i> influence synchronization dynamics of human neuronal oscillations.

Simola Jaana J Siebenhühner Felix F Myrov Vladislav V Kantojärvi Katri K Paunio Tiina T Palva J Matias JM Brattico Elvira E Palva Satu S

iScience 20220818 9

Neuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. We hypothesized that this variability could be partially explained by genetic polymorphisms in neuromodulatory genes. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether ...[more]

PMID: 36093050

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Project description:Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Dataset Information

Genetic polymorphisms in COMT and BDNF influence synchronization dynamics of human neuronal oscillations.

Publications

Genetic polymorphisms in <i>COMT</i> and <i>BDNF</i> influence synchronization dynamics of human neuronal oscillations.

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