How stress can curb the desire to eat in an animal model
August 16, 2019
Science Daily/University of Texas Health Science Center at Houston
Eating disorder researchers at The University of Texas Health Science Center at Houston (UTHealth) have discovered a neurocircuit in mice that, when activated, increased their stress levels while decreasing their desire to eat. Findings appear in Nature Communications.
The scientists believe their research could aid efforts to develop treatments for a serious eating disorder called anorexia nervosa, which has the highest mortality rate of any mental disorder, according to the National Institute of Mental Health. People with anorexia nervosa avoid food, severely restrict food, or eat very small quantities of only certain foods. Even when they are dangerously underweight, they may see themselves as overweight.
"We have identified a part of the brain in a mouse model that controls the impact of emotions on eating," said Qingchun Tong, PhD, the study's senior author and an associate professor in the Center for Metabolic and Degenerative Disease at McGovern Medical School at UTHealth.
Because mice and humans have similar nervous systems, Tong, the Cullen Chair in Molecular Medicine at UTHealth, believes their findings could shed light on the part of the human brain that regulates hunger.
The investigators believe they are among the first to demonstrate the role of this neurocircuit in the regulation of both stress and hunger.
While previous research has established that stress can both reduce and increase a person's desire to eat, the neural mechanisms that act on the regulation of eating by stress-related responses largely remain a mystery.
Tong's team focused on a neurocircuit connecting two parts of the mouse brain: the paraventricular hypothalamus, an eating-related zone in the brain, and the ventral lateral septum, an emotional zone in the brain. The neurocircuit acts as an on/off switch.
When researchers activated the neurocircuit, there was an increase in anxiety levels and a decrease in appetite. Conversely, when the investigators inhibited the neurocircuit, anxiety levels dropped and hunger increased.
The scientists used a research technique called optogenetics to turn the neurons in question on and off.
https://www.sciencedaily.com/releases/2019/08/190816191450.htm
Persistent low body weight in young kids increases risk for anorexia nervosa later
January 31, 2019
Science Daily/University of North Carolina Health Care
A new study has found that a persistent low body mass index (BMI) in children, starting as young as age 2 for boys and 4 for girls, may be a risk factor for the development of anorexia nervosa in adolescence.
In addition, the study, published in the February 2019 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, found that a persistent high BMI in childhood may be a risk factor for later development of bulimia nervosa, binge-eating disorder, and purging disorder. This large population study is based on analysis of data from 1,502 individuals who participated in the Avon Longitudinal Study of Parents and Children in the UK.
"Until now, we have had very little guidance on how to identify children who might be at increased risk for developing eating disorders later in adolescence," said Zeynep Yilmaz, PhD, study first author and an assistant professor of psychiatry and genetics at the UNC Center of Excellence for Eating Disorders in the University of North Carolina School of Medicine. "By looking at growth records of thousands of children across time, we saw early warning profiles that could signal children at risk."
Co-author Cynthia Bulik, PhD, Distinguished Professor of Eating Disorders also from UNC highlights, "Clinically, this means that pediatricians should be alert for children who fall off and stay below the growth curve throughout childhood. This could be an early warning sign of risk for anorexia nervosa. The same holds for children who exceed and remain above the growth curve -- only their risk is increased for the other eating disorders such as bulimia nervosa and binge-eating disorder."
Yilmaz said that although eating disorders are psychiatric in nature, the study highlights the need to also consider metabolic risk factors alongside psychological, sociocultural, and environmental components. "The differences in childhood body weight of adolescents who later developed eating disorders started to emerge at a very early age -- way too early to be caused by social pressures to be thin or dieting. A more likely explanation is that underlying metabolic factors that are driven by genetics, could predispose these individuals to weight dysregulation. This aligns with our other genetic work that has highlighted a metabolic component to anorexia nervosa."
Corresponding author of the study is Nadia Micali, MD, MRCPsych PhD, Full Professor at University of Geneva Faculty of Medicine and Head of Geneva University Hospitals' Division of Child and Adolescent Psychiatry.
"Our results also highlight the multi-factorial composition of eating disorders, as well as the need to develop early detection tools that could be used as part of routine checks by all pediatricians. Indeed, the earlier the problem is identified, the better it can be managed, especially if support is provided to the family as a whole, rather than just the individual," Micali said.
https://www.sciencedaily.com/releases/2019/01/190131143436.htm
Both obese and anorexic women have low levels of 'feel good' neurosteroid
November 10, 2017
Science Daily/University of Illinois at Chicago
Women at opposite extremes of the weight spectrum have low levels of the neuroactive steroid allopregnanolone, according to new research.
Previous research has linked low levels of allopregnanolone -- known to scientists as "allo" -- to depression and anxiety, which are common mood disorders associated with anorexia nervosa and obesity.
Allo is a metabolite of the hormone progesterone, one of the two major female hormones (the other being estrogen). Allo binds to receptors for the neurotransmitter gamma-aminobutyric acid (GABA) in the brain. These receptors are also the targets of anti-anxiety drugs such as benzodiazepines. Allo works by enhancing the signal produced when GABA binds to its receptor, generally producing a positive mood and feelings of well-being.
More than 50 percent of women with anorexia nervosa have depression or anxiety, and 43 percent of adults who are obese have depression.
Low levels of allo have been linked to depression and anxiety in numerous previous studies, including people with depression and post-traumatic stress disorder. But the chemical -- and its impact on mood -- has not been measured in anorexic or obese women.
"We are beginning to see more and more evidence that low allo levels are tightly linked to depression, anxiety, post-traumatic stress disorder and other mood disorders," said Graziano Pinna, associate professor of psychiatry in the University of Illinois at Chicago College of Medicine and an author on the paper. "To see that women with anorexia nervosa and obesity have low levels adds to the picture that the role of allo is under-recognized in mood disorders."
Pinna's colleagues, led by Dr. Karen Miller, professor of medicine at Harvard Medical School, recruited 12 women with anorexia nervosa and amenorrhea (stopped having their menstrual periods) whose body mass indices were less than 18.5; 12 normal-weight women with BMIs between 19 and 24; and 12 obese women with BMIs at 25 or higher. None of the women had received a diagnosis of depression or ever took antidepressants. The average age of the participants was 26 years old.
Participants completed questionnaires to assess for depression and anxiety and had blood drawn. Blood measurements of allo and other hormones were performed by Pinna's lab at the UIC. The lab had previously developed a novel, highly sensitive method technology to detect sex hormones and their metabolites. Pinna's lab is one of only three in the United States performing these measurements, which use gas chromatography and mass spectrometry to pick up extremely small levels of these chemicals in blood serum, saliva and brain tissue.
The researchers found that in women with anorexia nervosa and in obese women, blood levels of allo were 50 percent lower than they were in women with normal BMIs, and women who were clinically obese had allo levels approximately 60 percent lower than women with normal weights.
The researchers also found that levels of allo in all participants correlated with the severity of their depression and anxiety symptoms as measured by the questionnaires. Participants with lower levels of allo had greater severity of depression symptoms.
Progesterone levels were similarly low across all groups, suggesting that the decrease in allo in participants with anorexia nervosa and obesity may have been caused by improper functioning of enzymes responsible for the metabolism of progesterone into allo.
"Women with anorexia nervosa had low progesterone because they were amenorrheic, and the other two groups also had low progesterone levels because their blood was taken in the follicular phase when progesterone is naturally low," said Pinna. "That we found that obese women had lower allo levels than normal weight participants adds to growing evidence that this steroid is involved in depression and anxiety regardless of how much progesterone is available to begin with."
Pinna believes that the enzymes that convert progesterone into allo may not be working properly, causing decreases in allo that lead to mood disorders. "Drugs that increase the efficacy of these enzymes may be useful in helping to boost allo levels," he said. "But more research is needed to figure out exactly the deficit in the metabolism of progesterone into allo so that precision medicines using allo as a biomarker can be developed."
"Depression is an incredibly prevalent problem, especially in women, and also particularly at the extremes of the weight spectrum," said Miller. "The hope is that a greater understanding of mechanisms contributing to these disorders -- including abnormalities in the regulation of hormones and their neuroactive metabolites -- may lead to new targeted therapies in the future."
Pinna is leading preclinical studies of drugs designed to boost allo levels using several pharmacological strategies. These drugs have had promising effects in mouse models of PTSD and depression.
https://www.sciencedaily.com/releases/2017/11/171110164029.htm