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.