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2012 Compendium
Prevention Overrides Risky Behavior Gene
- Categorized in: June 2009 Issue
A family-based prevention program designed to help adolescents avoid substance use and other risky behavior proved especially effective for a group of young teens with a genetic risk factor contributing toward such behavior, according to a new study by researchers at the University of Georgia. The National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse supported the study, which appeared in the May/June issue of Child Development.
For 2 1/2 years, investigators monitored the progress of 11-year-olds enrolled in a family-centered prevention program called Strong African American Families (SAAF), and a comparison group. A DNA analysis showed some youths carried the short allele form of 5-HTTLPR. This fairly common genetic variation, found in over 40% of people, is known from previous studies to be associated with impulsivity, low self-control, binge drinking, and substance use.
The researchers found that adolescents with this gene who participated in the SAAF program were no more likely than their counterparts without the gene to have engaged in drinking, marijuana smoking, and sexual activity. Moreover, youths with the gene in the comparison group were twice as likely to have engaged in these risky behaviors as those in the prevention group.
The research team recruited 641 families in rural Georgia with similar demographic characteristics. They were divided randomly into two groups: 291 were assigned to a control group that received three mailings of health-related information, and 350 were assigned to the SAAF program, in which parents and children participated in seven consecutive weeks of two-hour prevention sessions. The parents learned about effective caregiving strategies that included monitoring, emotional support, family communication, and handling racial discrimination, which can contribute to substance abuse. The children were taught how to set and attain positive goals, deal with peer pressure and stress, and avoid risky activities.
Researchers conducted home visits with the families when the children were ages 11, 12, and 14, and collected data on parent-child relationships, peer relationships, youth goals for the future, and youth risk behavior. Two years later, the scientists collected DNA from saliva samples provided by the adolescents to determine whether they carried the short allele of 5HTTLPR. The results confirmed that the adolescents carrying this risk gene who were in the control group engaged in risky behaviors at a rate double that of their peers in the SAAF program.
New Labeling Required For OTC Pain Relievers
According to a final rule issued last month by the Food and Drug Administration, manufacturers of over-the-counter pain relievers and fever reducers will be required to revise their labeling to include warnings about potential safety risks such as internal bleeding and liver damage associated with the use of these popular drugs.
Products covered by the FDA action include acetaminophen and a class of drugs known as the nonsteroidal anti-inflammatory drugs. NSAIDs include aspirin, ibuprofen, naproxen, and ketoprofen. Acetaminophen is in a class by itself. The revised labeling applies to all OTC pain relievers and fever reducers, including those that contain one of these ingredients in combination with other ingredients such as cold medicines containing pain relievers or fever reducers.
“Acetaminophen and NSAIDs are commonly used drugs for both children and adults because they are effective in reducing fevers and relieving minor aches and pain such as headaches and muscle aches, “ said Charles Ganley, MD, director, FDA’s Office of Nonprescription Drugs at the Center for Drug Evaluation and Research. Dr Ganley stated further, “however, the risks associated with their use need to be clearly identifi ed on the label so that consumers taking these drugs are fully aware of the potential harm they can cause.”
Under the final rule, manufacturers must ensure that the active ingredients of these drugs are prominently displayed on the drug labels on both the packages and bottles. The labeling also must warn of the risks of stomach bleeding for NSAIDs and severe liver damage for acetaminophen.
Since 2006, some manufacturers have voluntarily revised their product labeling to identify these potential safety concerns. However, the voluntary changes to labeling do not address all of the labeling requirements in the new rule. For example, the new rule includes a warning on products containing acetaminophen that instructs consumers to ask a doctor before taking the blood thinning drug warfarin. The new rule requires all manufacturers to relabel their products within one year of today’s date.
Genetic Clues to Blood Pressure Uncovered
An international research team has identifi ed a number of unsuspected genetic variants associated with systolic blood pressure, diastolic blood pressure, and hypertension, suggesting potential avenues of investigation for the prevention or treatment of hypertension. The research was funded in part by the National Heart, Lung, and Blood Institute. The analysis of over 29,000 participants was presented at the American Society of Hypertension, Inc. scientific meeting on May 8, 2009, and published online in the journal Nature Genetics on May 10, 2009.
In a genome-wide association study, researchers scanned millions of common genetic variants of individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium to find variants associated with blood pressure and hypertension. The investigators identified a number of genetic variants or single-nucleotide polymorphisms associated with SBP, DBP, and hypertension. When they jointly analyzed their findings with those from the GWAS of over 34,000 participants in the Global BPgen Consortium, they identified 11 genes showing significant associations across the genome: four for SBP, six for DBP, and one for hypertension.
The blood pressure genes include ATP2B1, which encodes PMCA1, a cell membrane enzyme that is involved in calcium transport; CACNB2, which encodes part of a calcium channel protein; and CYP17A1, which encodes an enzyme that is necessary for steroid production. One detected variant is within the gene SH2B3, and has been associated with autoimmune diseases, hinting that pathways involved with the immune response may influence blood pressure.
Researchers found that the top 10 SNPs for systolic and diastolic blood pressure were each associated with around a 1 and 0.5 mm Hg increase in systolic and diastolic blood pressure, respectively. The prevalence of hypertension increased as the number of variants increased.
People who carry very few genetic blood pressure risk variants have blood pressure levels that are several mm Hg lower than those who carry multiple risk variants. A prolonged increase in DBP of only 5 mm Hg is associated with a 34% increase in risk for stroke and a 21% increase of coronary heart disease.
Risk of Autism Tied to Genes that Influence Brain Cells
In three recent studies, including the most comprehensive study of autism genetics to date, investigators, funded in part by the National Institutes of Health, have identified common and rare genetic factors that affect the risk of autism spectrum disorders. The results point to the importance of genes that are involved in forming and maintaining the connections between brain cells.
All three studies were genome-wide association studies, which are undertaken to find clues about the causes of complex disorders. The largest study, reported in Nature, involved more than 10,000 subjects, including individuals with ASD, their family members, and other volunteers from across the U.S. Previous studies of twins with ASD, other children with ASD, and their relatives, provided evidence of a strong genetic contribution. Yet until now, only a few genetic risk factors had been identified, and most of those turned out to be rare, with unclear signifi cance for ASD in the general population.
In their large study, researchers found several genetic variants that were commonly associated with ASD, all of which point to a spot between two genes on chromosome 5, called CDH9 and CDH10. Both genes encode cadherins—cell surface proteins that enable cells to adhere to each other. The researchers also found that a group of about 30 genes that encode cell adhesion proteins (including cadherins and neurexins) were more strongly associated with ASD than all other genes in their data set. In the developing brain, cell adhesion proteins enable neurons to migrate to the correct places and to connect with other neurons.
In a second study, researchers completed an independent search for small genetic variants associated with ASD. Published in the Annals of Human Genetics, the study provides a striking confirmation that ASD is associated with variation near CDH9 and CDH10.
Finally, in a third study, reported in Nature, researchers led a search for genes that were duplicated or deleted in individuals with ASD. In the rare cases where those variations occurred, many tended to affect genes involved in cell adhesion. Others tended to affect genes involved in the ubiquitin-proteasome system, a cellular waste disposal system that probably affects the turnover of adhesion proteins at the cell surface.
Previous, smaller genetic studies reported a connection between male-only autism and CNTNAP2, a type of neurexin. Together, the three new studies suggest that genetic differences in cell-to-cell adhesion could influence susceptibility to ASD on a large scale.
One in Four Had Major Depressive Episode Last Year
An estimated 16.5 million people aged 18 years or older experienced at least one major depressive episode (MDE) in the past year, and 64.5% of them received treatment, according to a new report released last month by the Substance Abuse and Mental Health Services Administration (SAMHSA).
The report showed that the rate of past year MDE was lower among persons aged 50 or older (5.85) than among those aged 18 to 25 (8.9%), or 26 to 49 (8.5%). Overall the rate of past year MDE was 7.5% for adults aged 18 or older. Also, the rate of MDE was higher for adults who perceived their overall health to be fair or poor (14.2%) than for those who described their health as excellent (4.3%).
Among those with past year MDE who received treatment for depression in the that calendar year, 68.8% saw or talked to a medical doctor or other health professional about depression and used prescription medication for depression. A quarter (245) of those with MDE who received treatment for depression saw or talked to a medical doctor or other health professional but did not use a prescription medication.
According to the report, one third of adults experiencing an MDE in the past year did not receive treatment during that period. The most frequently reported reasons for not receiving mental health services among these adults was their inability to afford the cost (43.2%), feeling that they were able to handle the problem on their own (29.3%), not knowing where to go for services (18.1%), not having the time (16.7%), health insurance that did not cover enough treatment (11.3%), and concerns about confi dentiality (11.1%).
The report is drawn from SAMHSA’s 2007 National Survey on Drug Use and Health (NSDUH), which collected data from a representative sample of approximately 45,000 non-institutionalized civilians adults throughout the United States.
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