Gut microbes may contribute to depression and anxiety in obesity
Study in mice links gut microbes with signs of negative feelings and brain chemistry
June 17, 2018
Science Daily/Joslin Diabetes Center
Like everyone, people with type 2 diabetes and obesity suffer from depression and anxiety, but even more so. Researchers now have demonstrated a surprising potential contributor to these negative feelings -- and that is the bacteria in the gut or gut microbiome, as it is known.
Studying mice that become obese when put on a high-fat diet, the Joslin scientists found that mice on a high-fat diet showed significantly more signs of anxiety, depression and obsessive behavior than animals on standard diets. "But all of these behaviors are reversed or improved when antibiotics that will change the gut microbiome were given with the high fat diet," says C. Ronald Kahn, M.D., co-Head of the Section on Integrative Physiology and Metabolism at Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School .
"As endocrinologists, we often hear people say that they feel differently when they've eaten different foods," notes Kahn, who is senior author on a paper in Molecular Psychiatry describing the research. "What this study says is that many things in your diet might affect the way your brain functions, but one of those things is the way diet changes the gut bacteria or microbes. Your diet isn't always necessarily just making your blood sugar higher or lower; it's also changing a lot of signals coming from gut microbes and these signals make it all the way to the brain."
His lab has long studied mice that are prone to developing obesity, diabetes and related metabolic diseases when given high-fat diets. Earlier this year, the team showed that at least part of this development is driven by changing bacteria in the gut microbiome. The condition was reversed in mice who were given antibiotics in their drinking water, which altered the microbiome.
In the most recent study, the Joslin scientists followed up by giving mice on a high-fat diet four classic lab animal behavioral tests, which are often employed in screening drugs for anxiety and depression. In each case, mice on high-fat diet showed higher signs of anxiety and depression than mice on a regular diet. However, when the mice were given antibiotics with the high fat diet, their behaviors returned to normal.
One of the ways the researchers showed this was an effect of the microbiome was by transferring gut bacteria from these experimental mice toto germ-free mice, who did not have any bacteria of their own. The animals who received bacteria from mice on a high-fat diet showed began to show increased levels of activity associated with anxiety and obsessive behavior. However, those who received microbes from mice on a high-fat diet plus antibiotics did not, even though they did not receive the antibiotics themselves. "This proves that these behaviors are driven to some significant extent by the gut microbiome," says Kahn.
But what exactly were the microbes doing? The Joslin looked for clues in two areas of the brain, the hypothalamus (which helps to control whole body metabolism) and the nucleus accumbens (which is important in mood and behavior).
"We demonstrated that, just like other tissues of the body, these areas of the brain become insulin resistant in mice on high-fat diets," Kahn says. "And this response to the high fat is partly, and in some cases almost completely, reversed by putting the animals by antibiotics. Again, the response is transferrable when you transfer the gut microbiome from mice on a high-fat diet to germ-free mice. So, the insulin resistance in the brain is mediated at least in part by factors coming from the microbiome."
The Joslin team went on to link the microbiome alterations to the production of certain neurotransmitters -- the chemicals that transfer signals across the brain.
Kahn and his colleagues are now working to identify specific populations of bacteria involved in these processes, and the molecules that the bacteria produce. The eventual goal is to find drugs or supplements that can help to achieve healthier metabolic profiles in the brain.
"Antibiotics are blunt tools that change many bacteria in very dramatic ways," Kahn says. "Going forward, we want to get a more sophisticated understanding about which bacteria contribute to insulin resistance in the brain and in other tissues. If we could modify those bacteria, either by putting in more beneficial bacteria or reducing the number of harmful bacteria, that might be a way to see improved behavior."
Overall, this study highlights how basic research that draws on expertise from multiple fields can lead in unexpected directions, Kahn emphasizes. "Understanding one area of biology, like diabetes and metabolism, can often give new and different perspectives in another field, like psychiatric and behavioral disorders," he says. "Even if that's not what you start out to do!"
https://www.sciencedaily.com/releases/2018/06/180617204413.htm
People who sleep less than 8 hours a night more likely to suffer from depression, anxiety
January 4, 2018
Binghamton University
Sleeping less than the recommended eight hours a night is associated with intrusive, repetitive thoughts like those seen in anxiety or depression, according to new research.
Binghamton University Professor of Psychology Meredith Coles and former graduate student Jacob Nota assessed the timing and duration of sleep in individuals with moderate to high levels of repetitive negative thoughts (e.g., worry and rumination). The research participants were exposed to different pictures intended to trigger an emotional response, and researchers tracked their attention through their eye movements. The researchers discovered that regular sleep disruptions are associated with difficulty in shifting one's attention away from negative information. This may mean that inadequate sleep is part of what makes negative intrusive thoughts stick around and interfere with people's lives .
"We found that people in this study have some tendencies to have thoughts get stuck in their heads, and their elevated negative thinking makes it difficult for them to disengage with the negative stimuli that we exposed them to," said Coles. "While other people may be able to receive negative information and move on, the participants had trouble ignoring it."
These negative thoughts are believed to leave people vulnerable to different types of psychological disorders, such as anxiety or depression, said Coles.
"We realized over time that this might be important -- this repetitive negative thinking is relevant to several different disorders like anxiety, depression and many other things," said Coles. "This is novel in that we're exploring the overlap between sleep disruptions and the way they affect these basic processes that help in ignoring those obsessive negative thoughts."
The researchers are further exploring this discovery, evaluating how the timing and duration of sleep may also contribute to the development or maintenance of psychological disorders. If their theories are correct, their research could potentially allow psychologists to treat anxiety and depression by shifting patients' sleep cycles to a healthier time or making it more likely a patient will sleep when they get in bed.
The paper, "Shorter sleep duration and longer sleep onset latency are related to difficulty disengaging attention from negative emotional images in individuals with elevated transdiagnostic repetitive negative thinking" was published in ScienceDirect.
https://www.sciencedaily.com/releases/2018/01/180104152947.htm
Combinations of certain personality traits may guard against depression and anxiety
November 29, 2017
Science Daily/University at Buffalo
People showing high levels of extraversion and conscientiousness may have protection against depression and anxiety, according to the results of a new study.
Though high levels of neuroticism put people at risk for depression and anxiety, if those same individuals are also highly extraverted and conscientious they could have a measure of protection against those disorders, according to the results of a new study by a team of University at Buffalo psychologists.
The findings, published in the Journal of Research in Personality, point to the importance of stepping away from focusing on single personality traits in clinical settings in favor of looking at how combinations of traits might work together to help either prevent or predict specific symptoms.
"We know individually how these traits relate to symptoms, but now we are beginning to understand how the traits might impact one another," says Kristin Naragon-Gainey, an assistant professor in UB's Department of Psychology and the paper's lead author with Leonard Simms, associate professor of psychology.
"We have to consider the whole person in order to understand the likelihood of developing negative symptoms down the road."
Neuroticism is the tendency to experience different negative emotions and to react strongly to stress. Along with extraversion and conscientiousness, it is among the "Big Five" personality traits, a group that also includes agreeableness and openness to experience.
People express each of the traits somewhere on a continuum. Someone high in extraversion would be very social, while another person low in extraversion would be much less outgoing. Conscientiousness, meantime, is the tendency to be organized, goal-oriented and non-impulsive.
The researchers interviewed 463 adult participants who reported receiving psychiatric treatment within the past two years. Each participant also completed numerous questionnaires. The study examined the traits of neuroticism, extraversion and conscientiousness because those three have the strongest associations with mood and anxiety disorders.
Naragon-Gainey says all things being equal, there are risks for disorders associated with certain traits, but a better image of what's at stake emerges when there's an understanding of how a group of behavioral tendencies might work together.
The results could provide an improved understanding of the mechanisms through which people develop mood disorders and explain the factors that might put someone at risk for symptoms like depression and anxiety.
Additionally, the findings might assist clinicians in how to capitalize on people's strengths with treatments that utilize what the study's results suggest are protective traits.
"I think there's a tendency in treatment and clinical psychology to concentrate on the problems and the negatives," says Naragon-Gainey. "If you utilize the pre-existing strengths that clients bring with them, it can positively affect treatment and the level of symptoms going forward, as well as reinforcing what the person is already doing well."
Conceptually, the strengths linked to high levels of extraversion and conscientiousness relate to the fact that social interactions and effective engagement in meaningful activities are rewarding for people, according to Naragon-Gainey.
"If someone has high levels of extraversion they might be very good at gathering social support or increasing their positive affectivity through social means," says Naragon-Gainey. "Similarly, conscientiousness has a lot to do with striving toward goals and putting plans in action, which can combat the withdrawal and avoidance that can go along with neuroticism."
https://www.sciencedaily.com/releases/2017/11/171129131357.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
Answer to young people's persistent sleep problems
September 28, 2017
Science Daily/James Cook University
A collaborative research project indicates high rates of sleep problems continuing through teenage years and into early adulthood -- but also suggests a natural remedy.
Dr. Yaqoot Fatima from JCU's Mount Isa Centre for Rural and Remote Health was associated with a study that tracked more than 3600 people from the age of 14 until they were 21.
"Just over a quarter of the 14-year-olds reported sleep problems, with more than 40 percent of those still having sleep problems at 21," said Dr. Fatima.
She said the causes of sleep problems were different at different ages.
"Maternal factors, such as drug abuse, smoking, depression and anxiety among mothers are the most significant predictors of adolescent sleep problems in their children, at 14-years-old. For all people studied, being female, having experienced early puberty, and being a smoker were the most significant predictors of sleep problems at 21 years."
She said adolescent depression or anxiety were linking factors for sleep problems between the two ages.
"It's a vicious circle. Depression and anxiety are well-established risk factors for sleep problems and people with sleep problems are often anxious or depressed," she said.
Dr. Fatima said that as well as the traditional factors, excessive use of electronic media is emerging as another significant risk.
"In children and adolescents, it's found to be strongly associated with later bedtime and shorter sleep duration, increasing the risk of developing sleep disturbances," she said.
Dr. Fatima said the study was worrying as it revealed a high incidence of persistent sleep problems and possible concurrent health problems among young people -- but it also strongly suggested an answer to the problem.
"Even allowing for Body Mass Index and other lifestyle factors, we found that an active lifestyle can decrease future incidence and progression of sleep problems in young subjects. So, early exercise intervention with adolescents might provide a good opportunity to prevent their sleep problems persisting into later life."
She said the next study being considered would look at what factors lead to young adults' sleep problems continuing as they grow older and how that might be prevented.
https://www.sciencedaily.com/releases/2017/09/170928094158.htm