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Genetic profile for dopamine signaling predicts brain functional reactivity to repetitive transcranial magnetic stimulation

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Abstract

Research integrating molecular and imaging data provides important insights into how the genetic profile associated with dopamine signaling influences inter-individual differences in brain functions. However, the effects of genetic variations in dopamine signaling on the heterogeneity of brain changes induced by repetitive transcranial magnetic stimulation (rTMS) still remain unclear. The current study examined the composite effects of genetic variations in dopamine-related genes on rTMS-induced brain responses in terms of the functional network connectivity and working memory performance. Healthy individuals (n = 30) participated in a randomized, double-blind, sham-controlled study with a crossover design of five consecutive days where active rTMS or sham stimulation sessions were administered over the left dorsolateral prefrontal cortex (DLPFC) of the brain. Participants were mostly women (n = 29) and genotyped for polymorphisms in the catechol-O-methyltransferase and D2 dopamine receptor genes and categorized according to their genetic composite scores: high vs. low dopamine signaling groups. Pre- and post-intervention data of resting-state functional magnetic resonance imaging and working memory performance were obtained from 27 individuals with active rTMS and 30 with sham stimulation sessions. The mean functional connectivity within the resting-state networks centered on the DLPFC increased in the high dopamine signaling group. Working memory performance also improved with rTMS in the high dopamine signaling group compared to that in the low dopamine signaling group. The present results suggest that genetic predisposition to higher dopamine signaling may be a promising neurobiological predictor for rTMS effects on cognitive enhancement.

Trial registration: ClinicalTrials.gov (NCT02932085).

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Acknowledgements

This study was supported by the National Research Foundation of Korea (NRF-2020R1A6A1A03043528 and NRF-2020M3E5D9080555 to IKL; 2019R1A2C1089515 to SML) and by the Health Fellowship Foundation to HH. The funders had no role study design, data collection, data analysis, data interpretation, manuscript preparation, manuscript review, manuscript approval, or decision to submit the manuscript for publication. The manuscript has not been previously published in print or electronic format and is not under consideration for publication elsewhere.

Funding

This article was funded by National Research Foundation of Korea (2020R1A6A1A0304352, 2020M3E5D9080555, 2019R1A2C1089515).

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Author notes

  1. Haejin Hong and Rye Young Kim contributed equally to the manuscript.

  2. Soo Mee Lim and Suji Lee shared last authorship.

Authors and Affiliations

  1. Ewha Brain Institute, Ewha W. University, Seoul, South Korea

    Haejin Hong, Rye Young Kim, Yumi Song, Chaewon Suh, Hyangwon Lee, In Kyoon Lyoo, Sujung Yoon & Suji Lee

  2. Graduate School of Pharmaceutical Sciences, Ewha W. University, Seoul, South Korea

    Rye Young Kim & In Kyoon Lyoo

  3. Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea

    Yumi Song, Chaewon Suh, Hyangwon Lee, In Kyoon Lyoo & Sujung Yoon

  4. Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

    In Kyoon Lyoo

  5. Department of Radiology, Ewha W. University College of Medicine, Seoul, South Korea

    Soo Mee Lim

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Contributions

IKL, SY, SML and SL designed the study. HH, RYK, SY, and SL acquired the data. HH, RYK, SML and SL analyzed the data. All authors interpreted the data. HH, RYK, SML and SL wrote the article. All authors reviewed the article. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

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Correspondence to Soo Mee Lim or Suji Lee.

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The study protocol was approved by the Institutional Review Board of Ewha W. University Mokdong Hospital.

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All patients provided written informed consent, in accordance with the 1964 Declaration of Helsinki.

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Hong, H., Kim, R.Y., Song, Y. et al. Genetic profile for dopamine signaling predicts brain functional reactivity to repetitive transcranial magnetic stimulation. Eur Arch Psychiatry Clin Neurosci 273, 99–111 (2023). https://doi.org/10.1007/s00406-022-01436-2

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