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

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