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Effects of the dopamine transporter gene on striatal functional connectivity in youths with attention-deficit/hyperactivity disorder

Published online by Cambridge University Press:  07 January 2020

Chi-Yung Shang ,
Hsiang-Yuan Lin  and
Susan Shur-Fen Gau Open the ORCID record for Susan Shur-Fen Gau [Opens in a new window]
Chi-Yung Shang
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Hsiang-Yuan Lin
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Susan Shur-Fen Gau*
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Graduate Institute of Brain and Mind Sciences and Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
*
Author for correspondence: Susan Shur-Fen Gau, E-mail: gaushufe@ntu.edu.tw
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Abstract

Background

The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD.

Method

After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions.

Results

Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype.

Conclusions

A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.

Keywords

Attention deficit hyperactivity disorderdopamine transporter genefunctional connectivityresting brain imagingstriatumvisual memory
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 5 , April 2021 , pp. 835 - 845
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Copyright
Copyright © Cambridge University Press 2020

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