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

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30:86:294-300. doi: 10.1016/j.pnpbp.2018.04.008. Epub 2018 Apr 20.

Abstract

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 ± 33.77, post-treatment DAT binding: 208.86 ± 28.75, p = 0.02) and right putamen (pre-treatment DAT binding: 314.41 ± 55.24, post-treatment DAT binding: 285.66 ± 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.

Keywords: ADHD; DAT1 gene; OROS-methylphenidate; [Tc-(99m)] TRODAT-1 SPECT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism
  • Brain Mapping
  • Central Nervous System Stimulants / therapeutic use*
  • Delayed-Action Preparations
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Female
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Male
  • Methylphenidate / therapeutic use*
  • Organotechnetium Compounds
  • Psychiatric Status Rating Scales
  • Radiopharmaceuticals
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome
  • Tropanes

Substances

  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Dopamine Plasma Membrane Transport Proteins
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • SLC6A3 protein, human
  • Tropanes
  • technetium Tc 99m TRODAT-1
  • Methylphenidate