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Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations

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Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a phenotipically and neurobiologically heterogeneous disorder. Deficiencies at different levels in response inhibition, differences in dopamine transporter genotype (DAT1) and various symptomatic presentations contribute to ADHD heterogeneity. Integrating these three aspects into a functional neuroimaging research could help unreval specific neurobiological components of more phenotipically homogeneous groups of patients with ADHD. During the Go-NoGo trial, we investigated the effect of the DAT1 gene using 3 T MRI in 72 ADHD cases and 24 (TD) controls that typically developed between the ages 8 and 15 years. In the total ADHD group, DAT1 predicted homozygosity for the 10R allele and hypoactivation in the anterior cingulate cortex and paracingulate cortex. There were no significant activation differences between DAT1 10R/10R homozygotes and 9R carriers in TD controls. Subjects with predominantly inattentive ADHD (ADHD-I) presentation with DAT1 10R/10R homozygous reduced neuronal activation during Go trial particularly in the frontal regions and insular cortex, and in the parietal regions during NoGo trial (brain regions reported as part of Default Mode Network- DMN). Additionally, DAT1 10R/10R homozygousness was associated with increased occipital zone activation during only the Go trial in the ADHD combined presentation (ADHD-C) group. Our results point the three main findings: 1) The DAT1 gene is 10R homozygous for differentiated brain activation in ADHD cases but not in the TD controls, supporting the DAT1 gene as a potential marker for ADHD, 2) The relationship between the DAT1 gene and the occipital regions in ADHD-C group which may reflect compensatory mechanisms, 3) The relationship between DAT1 gene and the reduced DMN suppression for 9R carriers probabaly stems from the ADHD-I group.

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Acknowledgements

We thank Dr. Cahide Aydın for contributions to the case enrollment process.

Funding

This work was partially supported by research grants from the following: Ege University Scientific Research Project Commission, Izmir, Turkey; the National Council for Scientific and Technological Development (CNPq, Brazil); and Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, Brazil. No financial or material support was received for this study.

Author information

Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Zubeyde Hanim Training and Research Hospital, Başkent University, Izmir, Turkey

    Ali Bacanlı

  2. Department of Child and Adolescent Psychiatry, Balıkesir University, Balıkesir, Turkey

    Gul Unsel-Bolat

  3. Department of Child and Adolescent Psychiatry, Medical Park Hospital, Samsun, Turkey

    Serkan Suren

  4. Department of Child and Adolescent Psychiatry, Faculty of Medicine, Fırat University, Elazığ, Turkey

    Kemal Utku Yazıcı

  5. Department of Radiology, Faculty of Medicine, Ege University, Izmir, Turkey

    Cem Callı

  6. Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey

    Duygu Aygunes Jafari & Buket Kosova

  7. ADHD Outpatient Program, Department of Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Luis Augusto Rohde

  8. National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil

    Luis Augusto Rohde

  9. Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ege University, Izmir, Turkey

    Eyup Sabri Ercan

Authors
  1. Ali Bacanlı
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  2. Gul Unsel-Bolat
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  3. Serkan Suren
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  4. Kemal Utku Yazıcı
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  5. Cem Callı
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  6. Duygu Aygunes Jafari
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  7. Buket Kosova
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  8. Luis Augusto Rohde
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  9. Eyup Sabri Ercan
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Contributions

E.S.E and L.A.R. designed the protocol of the study. A.B., S.S and K.U.Y. contributed to the case selection procedure and data collection. D.A. and B.K. were responsible for the genetic part of the study. C.C. provided neuroimaging part of the study. G.U.B. drafted the article, E.S.E. revised it critically for intellectual content. All authors approved final version of the manuscript.

Corresponding author

Correspondence to Gul Unsel-Bolat.

Ethics declarations

After the study procedures were described, the participants’ parents provided written informed consent. The Ethics Committee of Ege University in Turkey approved the study protocol.

Conflict of interest

Eyüp Sabri Ercan is on the advisory board of Sanofi Turkey. L. A. Rohde received grant or research support and served as a consultant and on the speakers’ bureaus of Eli Lilly and Co., Janssen, Medice, Novartis and Shire. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by Dr. Rohde received unrestricted educational and research support from the following pharmaceutical companies: Janssen, Novartis, and Shire. Dr. Rohde received travel grants from Shire to participate in the 2015 WFADHD congress. He received royalties from Artmed Editora and Oxford University Press. The other authors declare that they have no conflicts of interest to report.

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Bacanlı, A., Unsel-Bolat, G., Suren, S. et al. Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations. Brain Imaging and Behavior 15, 1103–1114 (2021). https://doi.org/10.1007/s11682-020-00437-w

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  • DOI: https://doi.org/10.1007/s11682-020-00437-w

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