Gene that leads to severe weight gain with antipsychotic treatment discovered

ScienceDaily (May 7, 2012) — Antipsychotic medications are increasingly prescribed in the US, but they can cause serious side effects including rapid weight gain, especially in children. In the first study of its kind, researchers at Zucker Hillside Hospital and the Feinstein Institute for Medical Research identified a gene that increases weight gain in those treated with commonly-used antipsychotic drugs.

See Also:Health & MedicineDiet and Weight LossObesityPersonalized MedicineMind & BrainDieting and Weight ControlObstructive Sleep ApneaSchizophreniaReferenceDopamine hypothesis of schizophreniaDiabetes mellitus type 2PsychopharmacologyStretch marks

These findings were published in the May issue of Archives of General Psychiatry.

Second-generation antipsychotics (SGAs) were used as the treatment in this study. SGAs are commonly used to treat many psychotic and nonpsychotic disorders. However, it is important to note that these SGAs are associated with substantial weight gain, including the development of obesity and other cardiovascular risk factors. The weight gain side effect of SGAs is significant because it often results in a reduced life expectancy of up to 30 years in those who suffer from chronic and severe mental illnesses. The weight gain also prompts some to stop taking the medication, adversely impacting their quality of life.

In this genome-wide association study (GWAS), researchers first evaluated a group of pediatric patients in the US being treated for the first time with antipsychotics. They then replicated the result in three independent groups of patients who were in psychiatric hospitals in the United States and Germany or participating in European antipsychotic drug trials. The gene that was identified to increase weight gain, MC4R or melanocortin 4 receptor, has been previously identified as being linked to obesity and type 2 diabetes. In the new study, it was found that patients gained up to 20 pounds when on treatment.

"This study offers the prospect of being able to identify individuals who are at greatest risk for severe weight gain following antipsychotic treatment," said Anil Malhotra, MD, investigator at the Zucker Hillside Hospital Department of Psychiatry Research and Feinstein Institute for Medical Research. "We hope that those who are at risk could receive more intensive or alternative treatment that would reduce the potential for weight gain and we are currently conducting studies to identify such treatment."

Additional Details About the Study

Researchers conducted the first GWAS of SGA-induced weight gain in patients carefully monitored for medication adherence who were undergoing initial treatment with SGAs. To confirm results, they next assessed three independent replication cohorts: 1) a cohort of adult subjects undergoing their first treatment with a single SGA (clozapine), 2) a cohort of adult subjects treated with the same SGAs as in our discovery sample, and 3) a cohort of adult subjects in the first episode of schizophrenia and enrolled in a randomized clinical trial of antipsychotic drugs. The discovery cohort consisted of 139 pediatric patients undergoing first exposure to SGAs. The 3 additional cohorts consisted of 73, 40, and 92 subjects. Patients in the discovery cohort were treated with SGAs for 12 weeks. Additional cohorts were treated for 6 and 12 weeks.

This GWAS yielded 20 single-nucleotide polymorphisms at a single locus exceeding a statistical threshold of P10-5. This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale GWAS of obesity in the general population. Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight during the 12-week trial. These results were replicated in 3 additional cohorts, with rs489693 demonstrating consistent recessive effects; meta-analysis revealed a genome-wide significant effect. Moreover, consistent effects on related metabolic indices, including triglyceride, leptin, and insulin levels were observed.

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Increased bodyweight after stopping smoking may be due to changes in insulin secretion

ScienceDaily (May 7, 2012) — Fear of putting on weight is one of the major reasons why smokers do not give up their habit. The reasons for this weight gain are believed to be in part due to metabolic changes in the body, but until now precise details of these changes were not known. On May 8, 2012, however, a researcher from Austria told delegates at the International Congress of Endocrinology/European Congress of Endocrinology that her work had shown that changes in insulin secretion could be related to weight gain after smoking cessation.

See Also:Health & MedicineSmokingDiet and Weight LossDiabetesObesityFitnessHormone DisordersReferenceBlood sugarDiabetes mellitus type 2HyperglycemiaGlycemic index

Dr. Marietta Stadler, from the Hietzing Hospital in Vienna, Austria, enrolled healthy smokers on a smoking cessation programme into a study in which they underwent three-hour oral glucose tolerance tests (OGTT) while still smoking and after a minimum of three and six months after giving up. Their body composition was also measured at the same time. The researchers measured beta cell

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Prepregnancy obesity linked to child test scores

ScienceDaily (May 8, 2012) — Women who are obese before they become pregnant are at higher risk of having children with lower cognitive function -- as measured by math and reading tests taken between ages 5 to 7 years -- than are mothers with a healthy prepregnancy weight, new research suggests.

See Also:Health & MedicineObesityDiet and Weight LossChildren's HealthMind & BrainChild DevelopmentIntelligenceChild PsychologyReferenceBirth weightNutrition and pregnancyMaternal bondStillbirth

In this large observational study, prepregnancy obesity was associated, on average, with a three-point drop in reading scores and a two-point reduction in math scores on a commonly used test of children's cognitive function.

Previous research has suggested that a woman's prepregnancy obesity can have a negative effect on fetal organs, such as the heart, liver and pancreas. Because fetal development is rapid and sensitive to a mother's physiological characteristics, Ohio State University researchers sought to find out whether a mother's obesity also could affect the fetal brain.

"One way you measure the effects on the brain is by measuring cognition," said Rika Tanda, lead author of the study and a doctoral candidate in nursing at Ohio State.

The research also supported findings in previous studies suggesting that several other conditions affect childhood cognition, including how stimulating the home environment is, family income and a mother's education and cognitive skills.

"The new piece here is we have a measure associated with the fetus's environment to add to that set of potential risk factors," said Pamela Salsberry, senior author of the study and a professor of nursing at Ohio State. "If we have a good way to understand the risks each child is born with, we could tailor the post-birth environment in such a way that they could reach their maximum capabilities."

The research appears online and is scheduled for future print publication in the Maternal and Child Health Journal.

The researchers used data from the National Longitudinal Survey of Youth (NLSY) 1979 Mother and Child Survey, a nationally representative sample of men and women who were 14-21 years old in December 1978. From that dataset, Tanda collected information on 3,412 children born to NLSY mothers who had been full-term births, were between 5 and almost 7 years old at the time of their interview and who had no diagnosed physical or cognition problems.

In addition to documenting a number of characteristics about the mothers and the family environment, the researchers gauged the children's cognitive function based on their performance on Peabody Individual Achievement Test reading recognition and math assessments.

The researchers calculated the mothers' body mass index (BMI) based on their reported heights and weights. More than half of mothers had normal BMIs before pregnancy, and 9.6 percent were obese, meaning they had a BMI of 30 or higher.

Controlling for all other variables, the analysis showed that maternal prepregnancy obesity was negatively associated with math and reading test scores. Children of obese women scored, on average, three points lower on reading and two points lower on math than did children of healthy-weight women. The mean reading score among all the children was 106.1 points and the mean math score was 99.9.

Though the score differences seem small, Tanda noted that these effects of prepregnancy obesity were equivalent to a seven-year decrease in the mothers' education and significantly lower family income, two other known risk factors that negatively affect childhood cognitive function.

Tanda said clinicians could use these findings to help encourage women patients of childbearing age to maintain a healthy weight, especially if they plan to get pregnant.

"This is a large population study, so at the individual level we can't say that one person's decision to change her weight will change her child's outcome," she said. "But these findings suggest that children born to women who are obese before pregnancy might need extra support."

Added Salsberry, "It's not only for their child's sake. It's also important for the health of the mother. But it is important to understand that maternal obesity during pregnancy could have implications for their children as well."

Without actual measures of women's and fetuses' insulin levels, inflammation and blood sugar readings, scientists can't say for sure how prepregnancy obesity might affect the fetal brain. But previous studies have suggested that a mother's impaired metabolic processes affect the fetal brain cell growth and formation of synapses.

The researchers also noted that obesity doesn't automatically equate to unhealthy.

"There may be two obese moms that in fact have very different metabolic profiles. For the purposes of this study, her weight is a stand-in for biological data that we would like to have but don't," Salsberry said.

Socioeconomic data from the study supported previous findings that several post-birth conditions can have a positive association with higher children's test scores. These include a stimulating home environment with plenty of books, a safe play environment and frequent family meals; higher family income; and higher maternal education levels and cognitive function. Girls and first-born children also performed better on the math and reading tests than did boys and younger siblings.

With all these data combined, Tanda said, the study also reveals how health disparities can have long-lasting effects.

"Young females who grow up poor, who have less access to healthy foods resulting in diets that are of poorer quality, are at higher risk of having children with disadvantages and repeating this cycle," she said.

The researchers are continuing to examine additional influences on childhood cognition, including race, sex and age differences among mothers.

This study was supported by a grant from the Ruth L. Kirschstein National Research Service Award predoctoral fellowship sponsored by the National Institute of Nursing Research.

Additional co-authors included Patricia Reagan and Muriel Fang of Ohio State's Department of Economics and the Center for Human Resource Research.

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US urges circumcision for soldiers to fight HIV in Africa

"Male circumcision is the best way to prevent new HIV infections in the military, the head of US anti-AIDS efforts Eric Goosby, pictured here in 2011, told a gathering of top army brass from Africa, Eastern Europe and central Asia. Studies show that circumcision can dramatically reduce HIV infections. (AFP Photo/Brendan Hoffman)" title

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FDA staff: Gilead's Truvada may help reduce HIV risk

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FDA favors first drug for HIV prevention

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FDA Favors HIV Pill for Prevention

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FDA review favors first drug for HIV prevention

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IUD Use Tied to Modest Weight Loss

HealthDay – 4 hrs ago TUESDAY, May 8 (HealthDay News) -- Women who use an intrauterine device (IUD) as birth control may not have to worry about gaining weight after the device is implanted, new research suggests.

Researchers compared the medical records of 223 women aged 15 to 44 who were using two different types of IUDs, following them for up to two years later.

About half of the women had a non-hormonal IUD containing copper while others used a hormonal IUD that released low levels of a progestin hormone called levonorgestrel (LNG) every day.

Women in both groups appeared to lose about 1 percent of their body weight in the first and second years of having an IUD.

The study was scheduled to be presented Monday at the American College of Obstetricians and Gynecologists annual meeting in San Diego.

"We really expected to see weight gain, and we didn't even expect that there would be weight loss," said study author Dr. Erika Kwock, an obstetrician and gynecologist at Kaiser Permanente Northern California in Santa Clara.

Although previous research has not found associations between hormonal or non-hormonal IUDs and weight gain, Kwock thought that the women in her study would put on pounds "just because over time people tend to gain weight regardless of contraception," she said.

However, Kwock pointed out that the weight loss among the women in her study is probably not a reliable result. Her study did not include enough women to allow for a statistical analysis to show that the women actually shed pounds.

Still, "the numbers are encouraging that there is not a weight difference for LNG IUDs and copper IUDs," Kwock said.

Dr. Jill Rabin, head of urogynecology at Long Island Jewish Medical Center in New Hyde Park, N.Y., said, "This study is interesting because it opens the door for more questions and more research."

But there were not enough women in the study to know if the IUDs were associated with weight changes, Rabin added.

"People are always worried about weight gain whenever you mention a hormone, even though weight gain is miniscule in our experience," Rabin said. "But I don't think we've answered the question, certainly not with the LNG, and not even with oral contraceptives."

Many women in the study received Kaiser insurance through work, Kwock said. Otherwise they were diverse and probably representative of the women nationwide, she added.

Kwock and study co-author Dr. Julie Livingston looked at a number of factors in the Kaiser medical records of these women, such as weight, age, race, medical conditions that might cause them to gain weight (such as diabetes and thyroid disease) and whether they were taking an antidepressant.

They found no differences for any of these factors between LNG and copper IUD users.

In addition, weight loss, albeit small, seemed to be similar between the LNG and copper IUD users; however this result might not be real, Kwock again cautioned.

Many women start on an IUD after they have had a baby, so Kwock and Livingston compared the proportion of women in each group who had received their IUD within two months of childbirth but found no differences.

The weight loss that the researchers saw in each group was not just due to the fact that some of the women were losing their "baby fat", Kwock said.

"A lot of the doctors we work with really recommend IUDs for new moms because they are busy and they don't have time to remember to take pills," Kwock said.

"One of my favorite forms of birth control is the LNG because it has so many benefits -- women get lighter periods and have less cramping, while the copper IUD can actually make periods more heavy," Kwock said.

However, some patients prefer copper IUDs and it really depends on the patient, Rabin said.

More than with IUDs, women really worry about gaining weight on the pill, and while this cannot be ruled out, most research does not find this to be the case, said Laureen Lopez, a family planning researcher at FHI 360 in Durham, N.C.

"We've concluded that women need to have more appropriate counseling. A lot of people unfortunately gain weight over time, and you need to look at dietary patterns and exercise and not blame a contraceptive for which there may be little evidence," Lopez said.

Because this study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.

More information

To learn more about IUDs, visit the American College of Obstetricians and Gynecologists.

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"Pink slime" may force BPI corporate staff cuts

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Half of U.S. Counties Have No Ob-Gyn: Study

HealthDay – 4 hrs ago TUESDAY, May 8 (HealthDay News) -- Nearly half of the counties in the United States lack a single obstetrician-gynecologist, a situation that may worsen as medical school graduates gravitate toward metropolitan areas, a new study indicates.

More than 9.5 million Americans live in areas without obstetrician-gynecologists (ob-gyns); this scarcity is more prevalent in rural pockets of the country, and particularly in the Midwest and South. However, some experts feel the spotty distribution of these specialists -- who assist in the births of 4 million babies each year and tend to the reproductive health of millions of women -- isn't necessarily a problem.

"If there's not an obstetrician in one county, but there's one in the next county, then it may not affect patient care at all," said Dr. Erin Tracy, an ob-gyn at Massachusetts General Hospital in Boston, who was not involved in the study. "It's a striking statistic . . . but I'm not sure how it affects actual access to care."

The study, authored by University of New Mexico researcher Dr. William Rayburn, is scheduled for presentation Tuesday at the American College of Obstetricians and Gynecologists (ACOG) annual meeting in San Diego.

Rayburn and his colleagues gathered data from the 2010 U.S. County Census File for adult and reproductive-age women and from the ACOG membership roster. They found that about 33,300 ob-gyns were practicing in the United States in 2010, representing 5 percent of a total of 661,400 physicians.

The average number of ob-gyns per 10,000 women dropped significantly from counties with cities in them to those with smaller towns and rural areas. Forty-nine percent of the country's 3,143 U.S. counties lacked a single ob-gyn, the investigators found.

"You're going to get less of every

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Health Tip: When Gardening Triggers Back Pain

HealthDay – 4 hrs ago (HealthDay News) -- Gardening is a great form of exercise, but it can also leave you with a painful backache.

The American Council on Exercise suggests how to garden without hurting yourself:

Use correct posture and form.Warm up before you garden with a 10-minute walk.Make sure all of your movements are smooth and steady.Keep your abdominal muscles taut.Lift with your legs (never your back).Don't twist your back while digging.Breathe regularly. Exhale when you lift, and inhale as you lower a heavy load.

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