Neurofunctional Effects of Methylphenidate and Atomoxetine in Boys with Attention-Deficit/Hyperactivity Disorder During Time Discrimination

Department of Child Psychiatry (ASm, AC, NB, KR). Electronic address: .
Biological psychiatry (Impact Factor: 10.26). 05/2013; 74(8). DOI: 10.1016/j.biopsych.2013.03.030
Source: PubMed


The catecholamine agonists methylphenidate and atomoxetine effectively treat attention-deficit/hyperactivity disorder (ADHD). Furthermore, dopamine agonists have shown to improve time estimation in ADHD, a core cognitive deficit. However, few have compared the effects of methylphenidate and atomoxetine on brain function in ADHD, and none during time estimation. Using single dose challenges, we investigated shared and drug-specific effects in ADHD adolescents on the neural substrates of time discrimination (TD).

Twenty ADHD adolescent male subjects were compared in a randomized double-blind cross-over design after single doses of methylphenidate, atomoxetine, and placebo in functional magnetic resonance imaging during TD. Normalization effects were assessed by comparing brain activation under each drug condition with that of 20 healthy age-matched control subjects.

Relative to control subjects, patients under placebo showed TD deficits and reduced activation of ventrolateral prefrontal cortex (VLPFC)/insula, inferior frontal cortex, and supplementary motor area. Performance differences were normalized only by methylphenidate, relative to both atomoxetine and placebo. Both medications, however, significantly upregulated right VLPFC/insula activation within patients and normalized its underactivation in ADHD boys under placebo relative to control subjects. The supplementary motor area and inferior frontal cortex activation differences that were observed under placebo were reduced by methylphenidate and atomoxetine, respectively, but neither survived rigorous testing for normalization.

While only methylphenidate had a drug-specific effect of improving TD performance deficits, both drugs significantly upregulated and normalized right VLPFC underactivation in ADHD boys under placebo relative to control subjects, suggesting shared effects of stimulants and nonstimulants on a key prefrontal dysfunction during timing.

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    • "For example, in the context of ADHD, although the disorder is understood to have multiple endophenotypes (Raz, 2004), the therapeutic actions of commonly used medications like methylphenidate (Ritalin) or dextroamphetamine (Adderall) are generally understood to occur through modulation of dopaminergic and noradrenergic pathways. Neuroimaging studies have identified structural and functional differences between the brains of stimulant-medicated and nonmedicated young people (Giedd et al., 2001; Smith et al., 2013), which are interpreted as evidence that psychostimulant medications exert their therapeutic effects through modulation of pathophysiological processes in the developing brain (Czerniak et al., 2013). Evidence of the adolescent brain's developmental malleability supports the importance of early 'normalizing' interventions because of the potential of the developing brain to respond to 'corrective' interventions (Singh and Rose, 2009). "
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    ABSTRACT: Drawing from ethnographic research among clinicians working with adolescents at a hospital psychiatric emergency department and outpatient clinic, and with interviews with adolescent psychiatric patients and their parents, we examine how psychiatric medicines function as socializing agents. Although psychiatric medications are thought to exert their main effects through direct biological action on neural circuitry, in fact, their use mobilizes specific kinds of moral discourse and social positioning that may have profound effects on sense of self, personhood, and psychological development. Specifically, our data reveal how clinical discourse around medications aims to enlist adolescents in becoming responsible, emotionally intelligent selves through learning to manage their medications. Among doctors, adolescents and their families, talk about psychiatric medications intertwines narratives of 'growing up' and 'getting well'. Our analysis of case studies from the clinic thus demonstrates that while psychiatric medications are explicitly designed to influence behavior by acting directly on the brain, they also act to structure adolescents' selves and social worlds through indirect, rather than direct causal pathways to the brain. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
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