Dietary interventions for Attention Deficit Hyperactivity Disorder (ADHD) have been both controversial and popular. Recently, a """"""""few foods"""""""" restriction diet was found to be efficacious relative to nutritional counseling in the treatment of ADHD. If these results were to be replicated, then a paradigmatic change in the management of ADHD would be in order. How does one perform a double blind study of a complex dietary treatment? How do dietary interventions compare to stimulant treatment and how might diet affect change at a neural level? In Phase I (2 years) of this R21/33 development grant, we plan to develop a Ruse Diet (RuD) that can be comparable to the Restriction diet (ReD) in impact on the child and family psychologically and which is similar in taste such that a blinded comparison is possible. We will then run a pilot double blind placebo controlled trial with 20 medication free children age 8 to 12 with ADHD. Our hypotheses are that the diet will be acceptable to families and the ReD will be superior to RuD in reducing parent ratings of ADHD behavior. Participants will have fMRI studies at baseline and at the end of the trial. For task fMRI, we will develop and determine the impact of the ReD vs. RuD diet on the regional activation levels and effective connectivity of the """"""""attention"""""""" networks while participants perform an anticipation-response conflict task. Effective connectivity analysis will be performed using dynamic causal modeling (DCM). We hypothesize that ReD vs. RuD will be increase activation levels within the ADHD network and in particular change strength of connectivity between the Intraparietal sulcus (IPS), the dorsolateral prefrontal cortex (DLPFC) and the ACC during the anticipation- response conflict task (connectivity changes will be reflected in both task and resting state data). Next, we will pilot a task in which the participants will also passively view pictures of foods that are either on or off the ReD, with pictures of household objects as controls. Such a task is well known to activate a """"""""reward"""""""" network of regions (ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC) that has been hypothesize to be involved in ADHD. In Phase II, (3 years), we will seek to determine the relative and combined efficacy of a restriction diet and methylphenidate in the treatment of ADHD, the acceptability/compliance of the diet to families and the child's perception of diet. We plan to randomize 40 children with ADHD (age 8-12) to a 2 (Placebo, methylphenidate) X 2 (ReD vs. RuD) for a five week period, obtaining task-fMRI based on our Phase I work. We will examine the efficacy of the ReD vs medication and determine if there any additive effects of ReD and medication vs. each treatment alone. We obtain fMRI using both the conflict and food imaging tasks both pre and post treatment. We seek to determine if the diet impacts functional connectivity (via DCM as above) in both the attention and reward networks and if such changes predict behavioral outcome.

Public Health Relevance

This study will compare a diet to stimulant medication in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and obtain functional magnetic imaging to determine the effects of both diet and medication on brain function. The study will seek to determine if restricting a range of foods has an impact on the symptoms of ADHD and if this improvement is related to specific brain changes in brain activity.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZMH1-ERB-D (03))
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Avenevoli, Shelli A
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University of Texas Health Science Center San Antonio
Schools of Medicine
San Antonio
United States
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