Effect of Homozygosity for 10-Repeat Allele at Dopamine Transporter Gene and Dopamine Transporter Density Assessed with 123IIPT SPECT on Response to Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: The symptoms of attention-deficit/hyperactivity disorder (ADHD) can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with ADHD. In present study, we investigated association between DAT density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane ([123I]IPT SPECT) and the homozygosity for 10-repeat allele at DAT1, and response to MPH in children with ADHD. METHODS: Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks. After the genotyping and SPECT were performed, we compared DAT density between ADHD children with and without the homozygosity for the 10-repeat allele at DAT1 and investigated correlation between the homozygosity for the 10-repeat allele and response to MPH. RESULTS: ADHD children with 10/10 genotype (n=7) had a significantly higher DAT density in basal ganglia than the children without 10/10 genotype (n=4)(Right: z=-2.65, p=0.008; Left: z=-2.65, p=0.008). We found that while only 28.6% (2/7) of the subject with 10/10 genotype showed good response (> or =50% improvement) to MPH treatment, 100% (4/4) of the subjects without 10/10 genotype showed good response to MPH treatment (chi2 test: F=5.238, df=1, p=0.022). CONCLUSION: Our findings support an association between homozygosity for the 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for the 10-repeat allele and poor response to MPH.

Dopamine Transporter Density of the Basal Ganglia Assessed with 123IIPT SPECT before and after Methylphenidate Treatment in Children with Attention Deficit Hyperactivity Disorder / 신경정신의학

OBJECTIVES: ADHD has been known as psychiatric disorder in childhood associated with dopamine dysregulation. The symptoms of ADHD can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). In present study, we investigated DAT density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT SPECT) in children with ADHD before and after treatment with methylphenidate. METHODS: Seven drug-naive children with ADHD and eight normal children were included in the study and performed SPECT 2 hours after an intravenous administration of [123I]IPT. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7 mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/ nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/ nonspecific DAT binding ratio of basal ganglia. RESULTS: Children with ADHD had a significantly greater increase of specific/nonspecific DAT binding ratio of right basal ganglia than normal children (Right:z=2.085, p=0.037;Left:z=1.506, p=0.132). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right:t=3.239, p=0.018;Left:t=3.133, p=0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. CONCLUSIONS: The data of this study using methylphenidate in children with ADHD support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Dopamine Transporter Density of the Basal Ganglia Assessed with I-123 IPT SPECT in Patients with Obsessive-Compulsive Disorder / 신경정신의학

OBJECTIVES: It has been suggested that dopamine as well as serotonin were related to the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies were performed to nivestigate brain regions and their association with dopamine in OCD patients. Recently, we have been able to monitor the density of the dopamine transporter (DAT) in the basal ganglia using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (I-123 IPT) SPECT, to evaluate the activity of the presynaptic dopamine function. In present study, we investigated the DAT density of the basal ganglia using I-123 IPT SPECT in patients with OCD. METHODS: Fifteen patients with OCD and nineteen normal control group were included in this study. We performed brain SPECT 2 hours after the intravenous administration of I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (I-123 IPT) and carried out both quantitative and qualitative analyses using the SPECT, which were reconstructed for the assessment of the specific/nonspecific DAT binding ratio in basal ganglia. We then investigated the correlation between the severity of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/nonspecific DAT binding ratio of basal ganglia. RESULTS: Patients with OCD showed a significantly increased specific/nonspecific DAT binding ratio in right basal ganglia compared with normal controls and did not show a significantly increased specific/nonspecific DAT binding ratio, and an increased tendency in the specific/nonspecific DAT binding ratio in left basal ganglia (Rt:Z=2.584, P=0.009, Lt:=1.873, P=0.060). We found no significant correlation between the total scores of the Y-BOCS and the specific/nonspecific DAT binding ratio of basal ganglia. CONCLUSIONS: The data of this study suggest that dopamine in basal ganglia plays an important role in fronto-subcortical circuit, which are already known as a site of the pathophysiological mechanism of OCD.

Dopamine Transporter Density of the Basal Ganglia in Children with Attention Deficit Hyperactivity Disorder Assessed with I-123 IPT SPECT / 대한정신약물학회지

OBJECTIVE: ADHD has been known as a psychiatric disorder in childhood associated with dopamine dysregulation. In the present study, we investigated dopamine transporter (DAT) density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (I-123-IPT)-SPECT in children with ADHD on the hypothesis that alterations of DAT density in the basal ganglia were suggestive of dopaminergic dysfunction in children with ADHD. METHODS: Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123-IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. We then investigated the correlation between ADHD Rating Scale (ARS) scores of children with ADHD and specific/nonspecific DAT binding ratios in the basal ganglia. RESULTS: Children with ADHD had significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children. However, no significant correlation were found between ARS scores of children with ADHD and specific/nonspecific DAT binding ratio of basal ganglia in children with ADHD. CONCLUSION: These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Dopamine Transporter Density of the Basal Ganglia Assessed with 123IIPT SPECT in Drug-Naive Children with Tourette's Disorder / 신경정신의학

OBJECTIVES: Previous studies in patients with Tourette's disorder suggested presynaptic dopaminergic dysfunction, demonstrating increased dopamine densities. In present study, we investigated dopamine transporter densities using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane(I-123-IPT)-SPECT in drug-naive children with Tourette's disorder and postulated that dopamine transporter density reflected dopamine concentrations. METHODS: Eight drug-naive children with Tourette's disorder and six normal children were included in the with the brain SPECT 2 hours after an intravenous administration of I-123-IPT. Obtained SPECT data were reconstructed for the assessment of specific/nonspecific dopamine transporter binding ratio of basal ganglia and were evaluated both quantitatively and qualitatively. We investigated correlation between total tic severity of children with Tourette's disorder assessed with YGTSS and specific/nonspecific binding ratio of basal ganglia. RESULTS: Drug-naive children with Tourette's disorder had a significantly greater increase of speciffic/nonspecific dopamine transporter binding ratio of left basal ganglia than normal children. However, no significant differences in specific/nonspecific dopamine transporter binding ratio of right basal ganglia were found between children with Tourette's disorder and normal children. Also, we found no significant correlation between total tic severity of children with Tourette's disorder and specific/ nonspecific binding ratio of basal ganglia. CONCLUSION: These findings support the hypothesis of dopamine dysregulation in presynaptic dopamine function of the basal ganglia in the pathophysiology of Tourette's disorder.