Update From the Medical Journals: October 2010
October 29, 2010
By Mary Pickett, M.D.
What's the latest news in the medical journals this month? Find out what your doctor is reading.
Children with attention-deficit hyperactivity disorder (ADHD) have symptoms that include difficulty paying attention, impulsive behavior, excessive restless or fidgety behavior. A new interesting study adds to the evidence that the ADHD behavior pattern comes from biologic differences in the brain, not from emotional stress or from unskilled parenting.
The study was published online in The Lancet on September 30. It found that genetic variations are more common in children with ADHD than in children without ADHD.
The study involved a fairly new area of science: "copy number variations." Humans have 23 pairs of matching chromosomes. Each chromosome is made up of a long strand of DNA proteins. Genes are segments of the DNA that carry instructions for cells. Usually, a chromosome has one copy of each gene that it carries. But sometimes one chromosome has extra copies of the same gene. This is a variation of "copy number." It is also possible for a chromosome to have no copies of a gene that we would expect it to carry, even though the other chromosome in its "pair" carries the gene. This is also a copy number variation.
Researchers compared the DNA from 366 children diagnosed with ADHD to the DNA from 1,047 children who were not diagnosed with ADHD. They found that 14% of children with ADHD had extra or missing copies of genes, compared with only 7% of children who did not have ADHD.
Genes tell cells how to make proteins. So having more copies or fewer copies of a gene could result in too much or too little of a specific protein. In the brain, proteins help to activate brain cells and to send messages between brain cells. It seems realistic that a change in "copy number" of a gene might create an imbalance of brain hormones or a difference in brain development. In fact, children with ADHD have less dopamine activity in the brain than is usual. It's possible that this new evidence helps explain why.
In recent years, studies of twins have shown that if one twin has ADHD, his or her sibling has about a 75% chance of having ADHD, too. Also, researchers have found several genes that are more common in the DNA of children with ADHD than in children without ADHD.
Although genetic differences contribute to many illnesses, they rarely act alone. Usually, genetic differences predispose a person to a condition but they don't cause illness until they combine with other factors. Other factors that may contribute to ADHD include diet, iron deficiency or possibly environmental exposures. Based on the research as a whole, it is likely that several factors may contribute to ADHD, not only genetics.
Osteoarthritis breaks down the smooth cartilage that lines joints. It is the most common form of arthritis.
The New England Journal of Medicine published a study in the October 14 issue about the effectiveness of an injected drug that acts against a chemical messenger involved in pain. (The study was released September 29 online). The drug, called tanezumab, is an antibody that targets nerve growth factor.
In the study, 450 people with osteoarthritis of the knee received either tanezumab or placebo injections. After four months, the group that got tanezumab reported pain scores that were 45% to 62% lower than the pre-treatment pain level for that group. The group that received placebo injections reported a 22% reduction in pain. With tanezumab, people reported improved function. Up to 93% of tanezumab-treated individuals felt better after treatment, compared with 44% of placebo-treated people. Also, people who took tanezumab needed to take less of other pain medicines.
The treatment, however, had some unexpected effects. X-rays revealed that 16 people who were treated with tanezumab had a rapid increase in the amount of cartilage and bone damage in the joints, including bone necrosis (death of bone tissue). These patients needed joint replacement surgery for the knee or hip. Researchers are wondering if the pain relief allowed these patients to over-work their damaged joints because they were not limited by pain.
For the time being, the U.S. Food and Drug Administration (FDA) has stopped additional testing of tanezumab because of the problems seen at the end of this study. Still, it is exciting to see a new approach to treating an old problem. Targeting nerve growth factor may be a powerful new tool in pain management, once we know how to most safely use a drug like tanezumab.
Mary Pickett, M.D. is an Associate professor at Oregon Health & Science University where she is a primary care doctor for adults. She supervises and educates residents in the field of Internal Medicine, for outpatient and hospital care. She is a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.