Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder - a single Photon Emission Computed Tomography with [Tc 99m ]TRODAT-1 study Claudia M. Szobot, a,b,c, ⁎ Ming Chi Shih, d Thais Schaefer, c Neivo Júnior, e Marcelo Q. Hoexter, d Ying Kai Fu, f Flávio Pechansky, b Rodrigo A. Bressan, d and Luis A.P. Rohde a a ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (POA), Estado do Rio Grande do Sul (RS), Brasil b Center for Drug and Alcohol Research, HCPA, UFRGS, POA, Brasil c Universidade Luterana do Brasil, Curso de Medicina. Canoas, RS, Brasil d Laboratório Interdisciplinar de Neurociências Clínicas (LINC), Universidade Federal de São Paulo (UFSP), São Paulo, Brasil e Irmandade Santa Casa de Misericórdia, POA, RS, Brasil f Institute of Nuclear Energy Research (INER), Long-Tan, Taiwan, Republic of China Received 17 October 2007; revised 12 December 2007; accepted 18 December 2007 Available online 10 January 2008 Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. Objectives: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DATavailability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Methods: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc 99m ]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale – version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. Results: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p b 0.001), and ∼ 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p b 0.001 for all analyses). Discussion: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies. © 2008 Elsevier Inc. All rights reserved. Keywords: Attention-Deficit/Hyperactivity Disorder; Substance Use Dis- orders; Methylphenidate; SPECT; Dopamine transporter; Adolescents Introduction Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent disorder worldwide, as recently documented by our group (Polanczyk et al., 2007). The disorder is characterized by excessive childhood onset inattention, hyperactivity and impulsivity (Amer- ican Psychiatric Association, 1994), tending to persist into adulthood. Affected subjects usually present with one or more comorbidities (Spencer et al., 2007). Individuals with ADHD are at higher risk for further Substance Use Disorder (SUD) (Molina et al., 1999; Biederman et al., 2006; Szobot et al., 2007) and a high ADHD prevalence is found in samples of adolescents with SUD (DeMilio, 1989; Kuperman et al., 2001; Horner and Scheibe, 1997). Moreover, ADHD affects SUD prognosis, being associated with both earlier and more frequent alcohol relapses (Ercan et al., 2003) and lower likelihood of cannabis treatment completion in adolescents (White et al., 2004). Several evidence-based guidelines suggest that stimulants are first line treatment for ADHD (Pliszka et al., 2006), but up to now little is known about clinical and brain effects of methylphenidate www.elsevier.com/locate/ynimg NeuroImage 40 (2008) 1195 – 1201 ⁎ Corresponding author. Programa de Déficit de Atenção/ Hiperatividade, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul., Rua Ramiro Barcelos, 2350. CEP: 90035-003. Porto Alegre, RS, Brasil. Fax: +55 51 3330 5813. E-mail address: cmszobot@terra.com.br (C.M. Szobot). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.12.050