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A three-pronged analysis confirms the association of the serotoninergic system with attention deficit hyperactivity disorder

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Abstract

Background

The serotonin transporter (SERT), encoded by the solute carrier family 6 number 4 (SLC6A4) gene, controls serotonin (5-HT) availability and is essential for the regulation of behavioral traits. Two SLC6A4 genetic variants, 5-HTTLPR and STin2, were widely investigated in patients with various neurobehavioral disorders, including attention deficit hyperactivity disorder (ADHD).

Methods

We analyzed the association of the 5-HTTLPR (L/S) and STin2 (10/12) variants, plasma 5-HT, and 5-hydroxyindole acetic acid (5-HIAA), as well as SERT messenger RNA (mRNA) with ADHD in the eastern Indian subjects. Nuclear families with ADHD probands (n = 274) and ethnically matched controls (n = 367) were recruited following the Diagnostic and Statistical Manual of Mental Disorders. Behavioral traits, executive function, and intelligence quotient (IQ) of the probands were assessed using the Conner's Parent Rating Scale – Revised, Parental Account of Children’s Symptoms (PACS), Barkley Deficit in Executive Functioning—Child and Adolescent Scale, and Wechsler Intelligence Scale for Children-III, respectively. After obtaining informed written consent, peripheral blood was collected to analyze genetic variants, plasma 5-HT, 5-HIAA, and SERT mRNA expression.

Results

ADHD probands showed a higher frequency of the 5-HTTLPR “L” allele and “L/L” genotype (P < 0.05), lower 5-HIAA level, and higher SERT mRNA expression. Scores for behavioral problems and hyperactivity were higher in the presence of the “S” allele and “S/S” genotype, while executive deficit was higher in the presence of the “L” allele. IQ score was lower in the presence of the STin2 “12” allele and L-12 haplotype.

Conclusion

Data obtained indicate a significant association of the serotoninergic system with ADHD, warranting further in-depth investigation.

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Data availability

Data generated for the study are presented in tabular format as Tables and Additional files. Further details on data will be available from the corresponding author on reasonable request.

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Acknowledgements

The authors are thankful to the study participants for volunteering in the study. In addition, we are grateful to Dr. Chinmay Saha for his help during the statistical analysis.

Funding

The host institute funded this study.

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Authors and Affiliations

  1. Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal, 700107, India

    Mahasweta Chatterjee, Sharmistha Saha, Swagata Sinha & Kanchan Mukhopadhyay

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  1. Mahasweta Chatterjee
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  2. Sharmistha Saha
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  4. Kanchan Mukhopadhyay
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Contributions

CM: investigation, data curation, formal analysis, writing–original draft. SSH: formal analysis. SSW: investigation. MK: conceptualization, supervision, writing–review and editing. All the authors approved the final manuscript.

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Correspondence to Kanchan Mukhopadhyay.

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Chatterjee, M., Saha, S., Sinha, S. et al. A three-pronged analysis confirms the association of the serotoninergic system with attention deficit hyperactivity disorder. World J Pediatr 18, 825–834 (2022). https://doi.org/10.1007/s12519-022-00614-5

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