Men's Health Women's Health Senior's Health Antioxidants Sports Nutrition Diet & Weight Loss Vitamins & Minerals Herbs Specialty Supplements Targeted Supplements Spa Products Anti-Aging Basics Body Systems Body Structure Book Store Pet Health My Recommendation My Favorite Articles Our Most Popular Specials Bargain Basement Brands

MSM

Health News Archive 668 - ADHD
<<back to structure/function index

Ritalin May Affect Children's Brain Development

Use of the attention deficit/hyperactivity disorder (ADHD) drug Ritalin by young children may cause long-term changes in the developing brain, suggests a new study of very young rats by a research team at Weill Cornell Medical College in New York City.

The study is among the first to probe the effects of Ritalin (methylphenidate) on the neurochemistry of the developing brain. This should serve as a warning for some and a reminder for others that powerful drugs may be approved for use, even by children, with very little testing.  Between 2 to18 percent of American children are thought to be affected by ADHD, and Ritalin, a stimulant similar to amphetamine and cocaine, remains one of the most prescribed drugs for the behavioral disorder.

"The changes we saw in the brains of treated rats occurred in areas strongly linked to higher executive functioning, addiction and appetite, social relationships and stress. These alterations gradually disappeared over time once the rats no longer received the drug," notes the study's senior author Dr. Teresa Milner, professor of neuroscience at Weill Cornell Medical College.

The findings, specially highlighted in the Journal of Neuroscience, suggest that doctors must be very careful in their diagnosis of ADHD before prescribing Ritalin. That's because the brain changes noted in the study might be helpful in battling the disorder but harmful if given to youngsters with healthy brain chemistry, Dr. Milner says.

In the study, week-old male rat pups were given injections of Ritalin twice a day during their more physically active nighttime phase. The rats continued receiving the injections up until they were 35 days old.

"Relative to human lifespan, this would correspond to very early stages of brain development," explains Jason Gray, a graduate student in the Program of Neuroscience and lead author of the study. "That's earlier than the age at which most children now receive Ritalin, although there are clinical studies underway that are testing the drug in 2- and 3-year olds."

The relative doses used were at the very high end of what a human child might be prescribed, Dr. Milner notes. Also, the rats were injected with the drug, rather than fed Ritalin orally, because this method allowed the dose to be metabolized in a way that more closely mimicked its metabolism in humans.

The researchers first looked at behavioral changes in the treated rats. They discovered that -- just as happens in humans -- Ritalin use was linked to a decline in weight. "That correlates with the weight loss sometimes seen in patients," Dr. Milner notes.

And in the "elevated-plus maze" and "open field" tests, rats examined in adulthood three months after discontinuing the drug displayed fewer signs of anxiety compared to untreated rodents. "That was a bit of a surprise because we thought a stimulant might cause the rats to behave in a more anxious manner," Dr. Milner says.

The researchers also used high-tech methods to track changes in both the chemical neuroanatomy and structure of the treated rats' brains at postnatal day 35, which is roughly equivalent to the adolescent period.

"These brain tissue findings revealed Ritalin-associated changes in four main areas," Dr. Milner says. "First, we noticed alterations in brain chemicals such as catecholamines and norepinephrine in the rats' prefrontal cortex -- a part of the mammalian brain responsible for higher executive thinking and decision-making. There were also significant changes in catecholamine function in the hippocampus, a center for memory and learning."

Treatment-linked alterations were also noted in the striatum -- a brain region known to be key to motor function -- and in the hypothalamus, a center for appetite, arousal and addictive behaviors. Dr. Milner stressed that, at this point in their research, it's just too early to say whether the changes noted in the Ritalin-exposed brain would be of either benefit or harm to humans.

"One thing to remember is that these young animals had normal, healthy brains," she says. "In ADHD-affected brains -- where the neurochemistry is already somewhat awry or the brain might be developing too fast -- these changes might help 'reset' that balance in a healthy way. On the other hand, in brains without ADHD, Ritalin might have a more negative effect. We just don't know yet."

One thing was clear: 3 months after the rats stopped receiving Ritalin, the animals' neurochemistry largely had resolved back to the pre-treatment state. "That's encouraging, and supports the notion that this drug therapy may be best used over a relatively short period of time, to be replaced or supplemented with behavioral therapy," Dr. Milner says. "We're concerned about longer-term use. It's unclear from this study whether Ritalin might leave more lasting changes, especially if treatment were to continue for years. In that case, it is possible that chronic use of the drug would alter brain chemistry and behavior well into adulthood."

This work was funded by the U.S. National Institutes of Health.

There are much safer alternatives such as increasing Omega-3 polyunsaturated fatty acids from fish and krill oil, decreasing Omega-6 oil from margarine, vegetable oils and processed foods (such as potato and tortilla chips, energy bars, fried foods and salad dressings), and the elimination of sugar from kids diets. 

Weill Cornell Medical College
Weill Cornell Medical College -- Cornell University's Medical School located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. The Medical College -- in its commitment to global health and education -- has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Salzburg, and Turkey. With the historic Weill Cornell Medical College in Qatar, the Medical School is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the world's first clinical trial for gene therapy for Parkinson's disease, and, most recently, the first indication of bone marrow's critical role in tumor growth. For more information, visit http://www.med.cornell.edu.

Abstract

Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.

Source: Press Release, July 19, 2007, New York-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT, Romeo RD, Brake WG, Torres-Reveron A, Milner TA. Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007 Jul 4;27(27):7196-207. PMID: 17611273

Also see: ADHD & Omega-3 Nutritional Deficiency.

back to top