OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. METHODS: This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. RESULTS: The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. CONCLUSION: These findings suggest that polymorphisms of the COMT gene can account for individual differences in neuro-chemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.
Attention Deficit Disorder with Hyperactivity* ; Catechol O-Methyltransferase ; Cerebellum ; Choline ; Creatine ; Genotype ; Gyrus Cinguli ; Humans ; Individuality ; Magnetic Resonance Spectroscopy* ; Methylphenidate* ; Prefrontal Cortex

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. METHODS: Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. RESULTS: The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. CONCLUSION: We found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.
Brain-Derived Neurotrophic Factor* ; Checklist ; Child ; Child Behavior ; Diagnostic and Statistical Manual of Mental Disorders ; Genotype ; Humans ; Neurodevelopmental Disorders ; Parents ; Problem Behavior ; Risk Factors*