Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate.

AIM: To examine theeffects on the brain of 2-month treatment withamethylphenidate extended-release formulation (OROS-MPH) using [Tc-99m] TRODAT-1SPECT in a sample of treatment-naïve adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). In addition, to assess whether risk alleles (homozygosity for 10-repeat allele at the DAT1 gene were associated with alterations in striatal DAT availability. METHODS: Twenty adolescents with ADHD underwent brain single-photon emission computed tomography (SPECT) scans with [Tc-99m] TRODAT-1 at baseline and two months after starting OROS-MPH treatment with dosages up to 1 mg/kg/day. Severity of illness was estimated using the Clinical Global Impression Scale (CGI-S) and DuPaul ADHD Rating Scale-Clinician version (ARS) before treatment,1 month and 2 months after initiating OROS-MPH treatment. RESULTS: Decreased DAT availability was found in both the right caudate (pretreatment DAT binding: 224.76 ±â€¯33.77, post-treatment DAT binding: 208.86 ±â€¯28.75, p = 0.02) and right putamen (pre-treatment DAT binding: 314.41 ±â€¯55.24, post-treatment DAT binding: 285.66 ±â€¯39.20, p = 0.05) in adolescents with ADHD receiving OROS-MPH treatment. Adolescents with ADHD who showed a robust response to OROS-MPH (n = 7) had significantly greater reduction of DAT density in the right putamen than adolescents who showed less robust response to OROS-MPH (n = 13) (p = 0.02). However, between-group differences by treatment responses were not related with DAT density in the right caudate. Risk alleles (homozygosity for the 10-repeat allele of DAT1 gene) in the DAT1 gene were not associated with alterations in striatal DAT availability. CONCLUSION: Two months of OROS-MPH treatment decreased DAT availability in both the right caudate and putamen. Adolescents with ADHD who showed a robust response to OROS-MPH had greater reduction of DAT density in the right putamen. However,our findings did not support an association between homozygosity for a 10-repeat allele in the DAT1 gene and DAT density, assessedusing[Tc-99m] TRODAT-1SPECT.

New alterations at potentially regulated regions of the Glial Derived Neurotrophic Factor gene in bipolar disorder.

INTRODUCTION: Glial Derived Neurotrophic Factor (GDNF) plays an important role in the survival and differentiation of neurons. We examined 5'upstream and 3' untranslated region of the GDNF gene by PCR amplification and direct sequencing to explore the effect of alteration in the potentially regulated part of GDNF in bipolar disorder. MATERIALS AND METHODS: Sixty-six patients with bipolar disorder, 27 first degree relatives of these patients and 56 healthy volunteers were screened for mutations and polymorphisms in GDNF gene. RESULTS: Seven previously reported polymorphisms and additional three novel allele variants of GDNF were detected. Association test of rs2075680 C>A SNP showed significant difference between patients and healthy subjects with higher allele frequency in healthy subjects performing Chi-square test. However, there was no significant difference after multiple test corrections between groups. There were no significant differences in association test of rs2075680 C>A SNP between first degree relatives and healthy volunteers/patients. rs142426358 T>C SNP was seen only in one patient with an early age of illness onset. New T>A alterations were found in chromosome locations 5:37812784 and 5:37812782 in two male bipolar disorder patients with age of illness onset 12 and 24 years. LIMITATIONS: The sample size was relatively small. DISCUSSION: Our study proposes the suggestive association between polymorphisms in the potential regulatory sites of GDNF and bipolar disorder.