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Study of the Long-term Impacts of Psychostimulants On the Brain

Study of the Long-term Impacts of Psychostimulants On the Brain (SLIPOB)听aims to assess the long-term impacts of psychostimulant medication on children with attention-deficit/hyperactivity disorder (ADHD).听Confirming that听cumulative psychostimulant dose has an impact on brain development would lead to a reassessment of the current clinical听practice of prescribing the maximum tolerated dose of psychostimulants when a lower dose may be sufficient to control听symptoms of ADHD.

Psychostimulant medications are the first-line pharmacotherapies for individuals with attention-deficit听/hyperactivity disorder (ADHD), a condition occurring in 5.9- 7.1% of school-aged children. Although these听medications work well, recent studies have raised concerns that long-term exposure to psychostimulants听may affect aspects of brain development. Indeed, chronic psychostimulant exposure in rodents is听associated with indices of oxidative stress and a loss of neurons in the hippocampus, a crucial area for听learning. Early exposure to psychostimulants has also been associated with persistent impairment in听hippocampal-dependent tasks. Studies that examined the issue have听mostly been cross-sectional and the rare longitudinal studies on this topic did not account for the听cumulative dose of psychostimulants. No studies have focused on the hippocampus in this context as its听role in ADHD has only recently been recognized.

Previously, Sherif Karama, MD, PhD听and his team have found a negative association between cumulative exposure to psychostimulants and the volume of听hippocampal subfields. Showing a potentially medication induced hippocampus change during a child鈥檚 development demands an urgent and thorough examination.听Results from this work could have a direct impact on the current prescription guidelines of discouraging weekend drug holidays and of prescribing the maximum tolerated dose of psychostimulants when a lower dose may be sufficient to control ADHD symptoms (minimal effective dose approach) while having less impact on hippocampus development.

Led by Dr. Karama, SLIPOB utilizes structural, diffusion-weighted and functional Magnetic Resonance Imaging (MRI) for longitudinal examination of the impact of psychostimulants on brain development, with a focus on hippocampal subfield development. Additionally, SLIPOB will examine long-term impacts of psychostimulants on hippocampal dependent cognition.听

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