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The norepinephrine transporter gene modulates intrinsic brain activity, visual memory, and visual attention in children with attention-deficit/hyperactivity disorder

Molecular Psychiatry volume 26, pages 4026–4035 (2021)Cite this article

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Abstract

The norepinephrine transporter gene (SLC6A2) and deficits in visual memory and attention were associated with attention-deficit/hyperactivity disorder (ADHD). The present study aimed to examine whether the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype affected the intrinsic brain activity in children with ADHD and whether these gene-brain modulations were associated with visual memory and attention in this population. A total of 96 drug-naive children with ADHD and 114 typically developing children (TDC) were recruited. We analyzed intrinsic brain activity with regional homogeneity (ReHo) and degree centrality (DC). Visual memory and visual attention were assessed by the delayed matching to sample (DMS) and rapid visual information processing (RVIP) tasks, respectively. The SNP genotyping of rs36011 and rs1566652 was performed. Children with ADHD showed lower ReHo and DC in the cuneus and lingual gyri than TDC. The TG haplotype was associated with significantly increased DC in the right precentral and postcentral gyri. Significant interactions of ADHD status and the TG haplotype were found in the right postcentral gyrus and superior parietal lobule for ReHo. For the ADHD-TG group, we found significant correlations of performance on the DMS and RVIP tasks with ReHo in bilateral precentral-postcentral gyri and the right postcentral gyrus-superior parietal lobule and DC in bilateral precentral-postcentral gyri. A novel gene-brain-behavior association was identified in which the intrinsic brain activity of the sensorimotor and dorsal attention networks was related to visual memory and visual attention in ADHD children with the SLC6A2 rs36011 (T)/rs1566652 (G) haplotype.

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Acknowledgements

This study was supported by grants NSC96-2628-B-002-069-MY3, NSC98-2314-B-002-051 -MY3, NSC99-2321-B-002-037, and NSC101-2321-B-002-079 from Ministry of Science and Technology (Taiwan) and grants NHRI-EX98-9407PC and NHRI-EX100-0008PI from National Health Research Institute (Taiwan). SNP genotyping was performed by the National Genotyping Center of Academia Sinica, Taiwan, and by the support from the Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.

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  1. Department of Psychiatry, National Taiwan University Hospital, and College of Medicine, Taipei, Taiwan

    Chi-Yung Shang, Hsiang-Yuan Lin & Susan Shur-Fen Gau

  2. Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, Taiwan

    Susan Shur-Fen Gau

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CYS and SSG contributed to concept and design of the study. CYS and SSG contributed to data acquisition. CYS, HYL, and SSG contributed to data analysis/interpretation. CYS contributed to drafting the manuscript, tables, and figures, which were critically reviewed by SSG. All authors read and approved the final version of the manuscript.

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Correspondence to Susan Shur-Fen Gau.

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Shang, CY., Lin, HY. & Gau, S.SF. The norepinephrine transporter gene modulates intrinsic brain activity, visual memory, and visual attention in children with attention-deficit/hyperactivity disorder. Mol Psychiatry 26, 4026–4035 (2021). https://doi.org/10.1038/s41380-019-0545-7

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