Attention deficit/hyperactivity disorder (ADHD) affects an increasing number of people worldwide, with an estimated 6.1 million children were living with ADHD in 2016, according to the National Survey of Children’s Health.
Now, MRI scans have revealed that children taking the common medication methylphenidate experience alterations in the distribution of white matter in the brain. This has led to the researchers warning doctors not to over-prescribe the medication and only use it when it is absolutely necessary, as the long-term effects of the medication are not yet known.
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Methylphenidate is a stimulant medication commonly prescribed for ADHD and works by blocking norepinephrine and dopamine transporters. Deficits in the prefrontal cortex are associated with ADHD symptoms, and increased dopamine and norepinephrine levels in the prefrontal cortex may have beneficial effects on the condition.
White matter is tissue found in the deepest part of the brain and facilitates quick thinking, learning, co-ordination between different parts of the brain, and the ability to walk and balance. The effects of methylphenidate on white matter, and by extension brain development, is not fully understood.
Lead researcher Liesbeth Reneman, MD, PhD, from the Department of Radiology and Nuclear Medicine, Academic Medical Center, at the University of Amsterdam, explained:
Previous studies all have tried to statistically control for the effects of ADHD medications, but we are the first to study medication-naïve patients in this context, which, of course is crucial if you want to know how ADHD medications effect the developing brain.”
Reneman’s new study, published in Radiology, which involved 50 treatment-naïve boys aged 10 to 12 and 48 adult men aged 23 to 40, all with ADHD across all types, showed that it took just four months of methylphenidate treatment to trigger changes in brain white matter in children. In contrast to this, no changes in white matter were seen in the young adult men included in the study, or in the study participants who received placebo treatments.
To chart any changes seen in the participants’ brains, they all underwent an MRI scan one week before their treatment began, and one week after their treatment stopped. Changes were found in the left hemisphere of the brain, with approximately double the rate of fractional anisotropy (nerve fiber density, size, and myelination).
The results suggest that the brain is susceptible to structural changes while it is still developing during childhood and adolescence, with the authors writing:
“The adolescent brain is a rapidly developing system maintaining high levels of plasticity. For instance, the maturation and development of white matter continues well into adulthood.”
“The results show that ADHD medications can have different effects on the development of brain structure in children versus adults. In adult men with ADHD, and both boys and adult men receiving placebo, changes in FA [fractional anisotropy] measures were not present, suggesting that the effects of methyphenidate on brain white matter are modulated by age,” Reneman said.
Reneman warned that they “do not yet know whether these effects are reversible or not and whether they are related to functional or behavioral changes over a longer period of time.”
“What our data already underscores is that the use of ADHD medications in children must be carefully considered until more is known about the long-term consequences of prescribing methylphenidate at a young age,” she said.
The study highlights the key results it produced through its experiments.
“In boys with attention-deficit/hyperactivity disorder (ADHD), four months of treatment with methylphenidate (MPH) was associated with increased white matter fractional anisotropy (FA) after 16 weeks.
“In adult men with ADHD and in both boys and adult men receiving placebo, changes in FA measures were not present, suggesting that the effects of MPH on brain white matter are modulated by age.”
The authors write that further investigations are needed to determine whether these results also apply to females, as well as children of different ages and adolescents, and that the age of a patient being prescribed medication for ADHD should be considered.
Bouziane, C., et al. (2019). White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with Attention-Deficit/Hyperactivity Disorder. RSNA Radiology. https://doi.org/10.1148/radiol.2019182528.