Investigators at Seoul National Hospital, and other centers in Seoul, Korea, studied the genetic, perinatal, and developmental risk factors in 147 children, ages 6 to 15 years, diagnosed with ADHD. Compared to a healthy control group of 502 children without ADHD, the ADHD-Combined subtype children showed more severe externalizing symptoms, more deficits in a continuous performance test, and were more likely to have comorbid disorders. Risk factors for both ADD-Inattentive and ADHD-Combined subtypes included maternal stress during pregnancy, postpartum depression, and changes in the primary caretaker during first 3 years. The ADD-I group was less likely to have received prenatal check-ups and more likely to have had postnatal medical illness than the ADHD-C group. The genotype frequencies of the dopamine transporter (DAT1) and serotonin transporter-linked polymorphisms were the same for the two subtypes. The inattentive subtype, ADD-I, differs from the combined subtype, ADHD-C, in having less severe symptoms, less comorbidity, and fewer environmental risk factors. [7]

COMMENTARY. In addition to the genetic factor, acquired environmental causes may contribute to the etiology of ADHD and these are classified according to the time of their occurrence: 1) pregnancy- and birth-related (pre- and perinatal) risk factors, and 2) childhood (postnatal) illnesses. Nutritional and dietary factors also play a role; of the numerous environmental causes listed, a deficiency of omega-3 fatty acid and treatment with supplemental fatty acid are receiving most attention [1, 2].

Treatment is occasionally determined by etiological environmental factors (e.g. thyroid, dietary), but usually a correction of deficient catecholamine metabolism using methylphenidate or amphetamine medication is the primary aim of treatment. Variability of response to medication may be explained by the occurrence and variability of environmental etiological factors. Gene-environment interaction is increasingly recognized as an important mechanism in the etiology and development of ADHD [3]. In therapy of ADHD, a combination of stimulant medication and supplemental omega-3 fatty acid may provide a better response than stimulant alone [4].

In previous clinical and animal studies, patients with the highest levels of motor activity were more likely to respond to methylphenidate therapy [5, 6]. In addition, the most active patients had the highest number of neurological soft-sign abnormalities, and in animals rendered hyperactive by prefrontal cerebral lesions, the more severe brain damage [5]. It is not surprising that the ADHD-C patient group in the Korean study [7] have more severe symptoms compared to the ADD-I subtype, greater comorbidity, and more evidence of environmental etiologic factors.