People Who Have Alcoholism Run in the Family Release More Dopamine in Expectation of Alcohol

Interesting findings that should be included in future treatments of alcohol use disorders. Forming situations where alcohol use isn’t expected could allow people to avoid a bad structure of incentives.

People with a family history of alcohol use disorder (AUD) release more dopamine in the brain’s main reward center in response to the expectation of alcohol than people diagnosed with the disorder, or healthy people without any family history of AUD, reports a new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

“This exaggerated reward center stimulation by expectation of alcohol may put the [individuals with family history] at greater risk of alcohol use disorder, and could be a risk factor in itself,” said first author Lawrence Kegeles, MD, PhD, of Columbia University.

The study examined a range of risk for AUD, including 34 healthy participants with no family history of AUD, 16 healthy participants with a family history of the disorder (referred to as the family-history positive, or FHP, group), and 15 participants diagnosed with AUD. Dr. Kegeles and colleagues used PET brain scanning to measure the amount of dopamine release in areas of the brain important for reward and addiction. The participants underwent the brain scans after receiving either an alcohol drink — a cocktail of vodka, tonic, and cranberry — or a placebo drink without the vodka. Although the participants didn’t know the order in which they would receive the drinks, if they received the placebo drink first they were cued into expecting the alcohol drink next.

All three groups had similar dopamine release-levels in response to the alcohol, suggesting that alcohol-induced dopamine release is normal in AUD. However, “we found that the FHP participants had a much more pronounced response to the placebo drink than the other groups, indicating that expectation of alcohol caused the FHP group to release more reward center dopamine,” said Dr. Kegeles. The release of dopamine into the reward center is thought to reinforce alcohol consumption and possibly contribute to risk of AUD.

Study: Leg Exercise is Crucial to Brain and Nervous System Health

The relation between having both a strong mind and body is shown again, this time with reasoning as to why leg day shouldn’t be skipped at the gym.

Groundbreaking research shows that neurological health depends as much on signals sent by the body’s large, leg muscles to the brain as it does on directives from the brain to the muscles. Published today in Frontiers in Neuroscience, the study fundamentally alters brain and nervous system medicine — giving doctors new clues as to why patients with motor neuron disease, multiple sclerosis, spinal muscular atrophy and other neurological diseases often rapidly decline when their movement becomes limited.

“Our study supports the notion that people who are unable to do load-bearing exercises — such as patients who are bed-ridden, or even astronauts on extended travel — not only lose muscle mass, but their body chemistry is altered at the cellular level and even their nervous system is adversely impacted,” says Dr. Raffaella Adami from the Università degli Studi di Milano, Italy.

The study involved restricting mice from using their hind legs, but not their front legs, over a period of 28 days. The mice continued to eat and groom normally and did not exhibit stress. At the end of the trial, the researchers examined an area of the brain called the sub-ventricular zone, which in many mammals has the role of maintaining nerve cell health. It is also the area where neural stem cells produce new neurons.

Limiting physical activity decreased the number of neural stem cells by 70 percent compared to a control group of mice, which were allowed to roam. Furthermore, both neurons and oligodendrocytes — specialized cells that support and insulate nerve cells — didn’t fully mature when exercise was severely reduced.

The research shows that using the legs, particularly in weight-bearing exercise, sends signals to the brain that are vital for the production of healthy neural cells, essential for the brain and nervous system. Cutting back on exercise makes it difficult for the body to produce new nerve cells — some of the very building blocks that allow us to handle stress and adapt to challenge in our lives.

“It is no accident that we are meant to be active: to walk, run, crouch to sit, and use our leg muscles to lift things,” says Adami. “Neurological health is not a one-way street with the brain telling the muscles ‘lift,’ ‘walk,’ and so on.”

The researchers gained more insight by analyzing individual cells. They found that restricting exercise lowers the amount of oxygen in the body, which creates an anaerobic environment and alters metabolism. Reducing exercise also seems to impact two genes, one of which, CDK5Rap1, is very important for the health of mitochondria — the cellular powerhouse that releases energy the body can then use. This represents another feedback loop.

These results shed light on several important health issues, ranging from concerns about cardio-vascular impacts as a result of sedentary lifestyles to insight into devastating diseases, such as spinal muscular atrophy (SMA), multiple sclerosis, and motor neuron disease, among others.

Link Between Local Temperature Increases and More Antibiotic Resistance Found

A significant note with the threat of climate change looming.

Seeking to better understand the distribution of antibiotic resistance across the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital and the University of Toronto have found that higher local temperatures and population densities correlate with a higher degree of antibiotic resistance in common bacterial strains. The findings were published today in Nature Climate Change.

“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”

“Estimates outside of our study have already told us that there will already be a drastic and deadly rise in antibiotic resistance in coming years,” says the paper’s co-senior author John Brownstein, PhD, who is Chief Innovation Officer and director of the Computational Epidemiology Group at Boston Children’s and professor of pediatrics at Harvard Medical School (HMS). “But with our findings that climate change could be compounding and accelerating an increase in antibiotic resistance, the future prospects could be significantly worse than previously thought.”

During their study, the team assembled a large database of U.S. antibiotic resistance information related to E. coli, K. pneumoniae, and S. aureus, pulling from various streams of hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial pathogens from 602 unique records across 223 facilities and 41 states.

Not surprisingly, when looking at antibiotic prescription rates across geographic areas, the team found that increased prescribing was associated with increased antibiotic resistance across all the pathogens that they investigated.

Then, comparing the database to latitude coordinates as well as mean and medium local temperatures, the team found that higher local average minimum temperatures correlated the strongest with antibiotic resistance. Local average minimum temperature increases of 10 degrees Celsius were found to be associated with 4.2, 2.2 and 3.6 percent increases in antibiotic resistant strains of E. coli, K. pneumoniae, and S. aureus, respectively.

More unsettling still, when looking at population density, the team found that an increase of 10,000 people per square mile was associated with three and six percent respective increases in antibiotic resistance in E. coli and K. pneumoniae, which are both Gram-negative species. In contrast, the antibiotic resistance of Gram-positive S. aureus did not appear to be significantly affected by population density.

“Population growth and increases in temperature and antibiotic resistance are three phenomena that we know are currently happening on our planet,” says the study’s co-senior author Mauricio Santillana, PhD, who is a faculty member in the Computational Health Informatics Program at Boston Children’s and an assistant professor at HMS. “But until now, hypotheses about how these phenomena relate to each other have been sparse. We need to continue bringing multidisciplinary teams together to study antibiotic resistance in comparison to the backdrop of population and environmental changes.”

MacFadden says the transmission factor is of particular interest for further scientific research.

“As transmission of antibiotic resistant organisms increases from one host to another, so does the opportunity for ongoing evolutionary selection of resistance due to antibiotic use,” MacFadden says. “We hypothesize that temperature and population density could act to facilitate transmission and thus increases in antibiotic resistance.”

Simple Lung Cancer Scans That Could Save Thousands of Lives a Year

Cancer can be exponentially easier to treat or cure when it’s caught early.

A new study found that fewer than 2 percent of heavy smokers in the U.S. get recommended lung cancer screenings, an imaging test that can catch tumors when they are small and potentially curable. The numbers fall far short of screening for other types of cancer, including mammograms and colonoscopies—both procedures that are much more uncomfortable than the CT scan used to detect tiny tumors in the lungs.

Lung cancer is the leading cause of cancer death in the U.S., killing an estimated 150,000 Americans each year. For the past five years, such groups as the U.S. Preventive Services Task Force and the American Society of Clinical Oncology have urged people aged 55 or older who have smoked a pack a day (or the equivalent) for three decades or more to get checked for early stage disease. Medicare, the U.S. government’s insurance program for the elderly, pays for the procedure. None of it has made an impact.

“It’s still truly abysmal,” said Danh Pham, chief fellow of hematology/oncology at the University of Louisville’s cancer center in Kentucky, who will present the findings at the ASCO cancer meeting next month in Chicago. “We would like to make this a true call to action, whether it’s for more education or more research, to know why this disparity exists for lung cancer.”

It took a while for public health officials to start recommending routine lung cancer screening, because of questions about its accuracy and its ability to make a difference once the disease was detected. Subsequent studies confirmed the benefits for the heaviest smokers, with the use of screening intended for those most vulnerable to tumors.

The researchers analyzed registry data for everyone who underwent lung cancer screening in 2016 and found that 141,260 of the 7.6 million people eligible, or 1.9 percent, received it. By comparison, from 60 percent to 80 percent of eligible people get screening for breast, cervical and colon cancer, said Bruce Johnson, president of the American Society of Clinical Oncology and chief clinical research officer at the Dana-Farber Cancer Institute in Boston.

The testing shortfall could stem from primary care doctors’ failure to refer high-risk patients to one of 1,800 approved centers nationwide which provide the service. Psychological issues could also play a role, including fear of being diagnosed with a disease that smokers are constantly reminded of, Pham said.

“It’s very difficult to get patients to have this conversation with their doctors because of the stigma,” he said. “People may not want to know if they have lung cancer because it could confirm they’ve made bad lifestyle choices.”

Lung cancer deaths exceed those from breast, colon, pancreas and prostate cancer combined. There are very compelling reasons to get screened, said Johnson.

“If you screened the entire population of the U.S. who fit the criteria for having smoked enough and being the appropriate age, which is about 8 million people, you could save about 12,000 lives a year,” he said. “The majority of lung cancers picked up are early stage,” and finding them before the malignant cells spread reduces the risk of dying by about 20 percent, he said.

Hard Evidence that Meditation and Certain Breathing Exercises Can Sharpen the Mind

The mind can also become out of shape if it isn’t exercised regularly, similar to the body. Meditation may be worth looking at more in a world where it takes considerable mental strength to not give into a lot of technological distraction.

It has long been claimed by Yogis and Buddhists that meditation and ancient breath-focused practices, such as pranayama, strengthen our ability to focus on tasks. A new study by researchers at Trinity College Dublin explains for the first time the neurophysiological link between breathing and attention.

Breath-focused meditation and yogic breathing practices have numerous known cognitive benefits, including increased ability to focus, decreased mind wandering, improved arousal levels, more positive emotions, decreased emotional reactivity, along with many others. To date, however, no direct neurophysiological link between respiration and cognition has been suggested.

The research shows for the first time that breathing — a key element of meditation and mindfulness practices — directly affects the levels of a natural chemical messenger in the brain called noradrenaline. This chemical messenger is released when we are challenged, curious, exercised, focused or emotionally aroused, and, if produced at the right levels, helps the brain grow new connections, like a brain fertiliser. The way we breathe, in other words, directly affects the chemistry of our brains in a way that can enhance our attention and improve our brain health.

The study, carried out by researchers at Trinity College Institute of Neuroscience and the Global Brain Health Institute at Trinity, found that participants who focused well while undertaking a task that demanded a lot of attention had greater synchronisation between their breathing patterns and their attention, than those who had poor focus. The authors believe that it may be possible to use breath-control practices to stabilise attention and boost brain health.

Michael Melnychuk, PhD candidate at the Trinity College Institute of Neuroscience, Trinity, and lead author of the study, explained: “Practitioners of yoga have claimed for some 2,500 years, that respiration influences the mind. In our study we looked for a neurophysiological link that could help explain these claims by measuring breathing, reaction time, and brain activity in a small area in the brainstem called the locus coeruleus, where noradrenaline is made. Noradrenaline is an all-purpose action system in the brain. When we are stressed we produce too much noradrenaline and we can’t focus. When we feel sluggish, we produce too little and again, we can’t focus. There is a sweet spot of noradrenaline in which our emotions, thinking and memory are much clearer.”

“This study has shown that as you breathe in locus coeruleus activity is increasing slightly, and as you breathe out it decreases. Put simply this means that our attention is influenced by our breath and that it rises and falls with the cycle of respiration. It is possible that by focusing on and regulating your breathing you can optimise your attention level and likewise, by focusing on your attention level, your breathing becomes more synchronised.”

The research provides deeper scientific understanding of the neurophysiological mechanisms which underlie ancient meditation practices. The findings were recently published in a paper entitled ‘Coupling of respiration and attention via the locus coeruleus: Effects of meditation and pranayama’ in the journal Psychophysiology. Further research could help with the development of non-pharmacological therapies for people with attention compromised conditions such as ADHD and traumatic brain injury and in supporting cognition in older people.

There are traditionally two types of breath-focused practices — those that emphasise focus on breathing (mindfulness), and those that require breathing to be controlled (deep breathing practices such as pranayama). In cases when a person’s attention is compromised, practices which emphasise concentration and focus, such as mindfulness, where the individual focuses on feeling the sensations of respiration but make no effort to control them, could possibly be most beneficial. In cases where a person’s level of arousal is the cause of poor attention, for example drowsiness while driving, a pounding heart during an exam, or during a panic attack, it should be possible to alter the level of arousal in the body by controlling breathing. Both of these techniques have been shown to be effective in both the short and the long term.

Ian Robertson, Co-Director of the Global Brain Health Institute at Trinity and Principal Investigator of the study added: “Yogis and Buddhist practitioners have long considered the breath an especially suitable object for meditation. It is believed that by observing the breath, and regulating it in precise ways — a practice known as pranayama — changes in arousal, attention, and emotional control that can be of great benefit to the meditator are realised. Our research finds that there is evidence to support the view that there is a strong connection between breath-centred practices and a steadiness of mind.”

“Our findings could have particular implications for research into brain ageing. Brains typically lose mass as they age, but less so in the brains of long term meditators. More ‘youthful’ brains have a reduced risk of dementia and mindfulness meditation techniques actually strengthen brain networks. Our research offers one possible reason for this — using our breath to control one of the brain’s natural chemical messengers, noradrenaline, which in the right ‘dose’ helps the brain grow new connections between cells. This study provides one more reason for everyone to boost the health of their brain using a whole range of activities ranging from aerobic exercise to mindfulness meditation.”

Prolonged Exposure to Air Pollution Linked to Negative Genetic Changes in Mice

Air pollution — consistently being shown to be a pretty significant issue to public health.

Prolonged exposure to particulate matter in air pollution in the Los Angeles Basin triggered inflammation and the appearance of cancer-related genes in the brains of rats, a Cedars-Sinai study has found.

While previous research has documented the association between air pollution and a variety of diseases, including cancer, the study found markers indicating certain materials in coarse air pollution — nickel, in particular — may play a role in genetic changes related to disease development, said Julia Ljubimova, MD, PhD.

Ljubimova, director of the Nanomedicine Research Center at Cedars-Sinai, is the lead author of the paper, published April 9 in Scientific Reports.

“This study, which looked at novel data gathered in the Los Angeles area, has significant implications for the assessment of air quality in the region, particularly as people are exposed to air pollution here for decades,” Ljubimova said.

44 Genomic Variations Linked to Major Depression in New Research

Genetic variations (variants) are the roughly 0.5% share of DNA that makes individuals unique, as about 99% of human DNA is shared across humans. The word genome represents the entire set of genetic material someone’s made of. With that being said, this research is important because major depressive disorder can be a really crippling affliction, and the more that’s known about it, the more effectively it can be treated or prevented.

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A new meta-analysis of more than 135,000 people with major depression and more than 344,000 controls has identified 44 genomic variants, or loci, that have a statistically significant association with depression.

Of these 44 loci, 30 are newly discovered while 14 had been identified in previous studies. In addition, the study identified 153 significant genes, and found that major depression shared six loci that are also associated with schizophrenia.

Results from the multinational, genome-wide association study were published April 26 in Nature Genetics.

The study was an unprecedented global effort by over 200 scientists who work with the Psychiatric Genomics Consortium. Co-leaders of the study are Patrick F. Sullivan, MD, FRANZCP, Yeargen Distinguished Professor of Psychiatry and Genetics and Director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine; and Naomi Wray, PhD, Professorial Research Fellow at the University of Queensland in Australia.

“This study is a game-changer,” Sullivan said. “Figuring out the genetic basis of major depression has been really hard. A huge number of researchers across the world collaborated to make this paper, and we now have a deeper look than ever before into the basis of this awful and impairing human malady. With more work, we should be able to develop tools important for treatment and even prevention of major depression.”

“We show that we all carry genetic variants for depression, but those with a higher burden are more susceptible,” Wray said. “We know that many life experiences also contribute to risk of depression, but identifying the genetic factors opens new doors for research into the biological drivers.”

“This pioneering study is incredibly important, for two reasons,” said Josh Gordon, MD, PHD, Director of the U.S. National Institute of Mental Health. Dr. Gordon was not an author on this paper.

“First, it reaffirms the value of large-scale collaborations, particularly in identifying the complex genetics underlying psychiatric illness. Second, it confirms the genetic roots for depression, offering important biological clues that we hope will lead to new and better treatments.”

“Major depression represents one of the world’s most serious public health problems,” said Steven E. Hyman, MD, former director of the U.S. National Institute of Mental Health who is now Director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. Dr. Hyman was not an author on this paper. “Despite decades of effort there have been, until now, only scant insights into its biological mechanisms. This unfortunate state of affairs has severely impeded treatment development, leaving the many people who suffer from depression with limited options. This landmark study represents a major step toward elucidating the biological underpinnings of depression,” Hyman said.

Other findings of the study include:

  • The results can be used for improved therapies — targets of known antidepressant medications were enriched in the genetic findings
  • The genetic basis of depression overlaps importantly with other psychiatric disorders like bipolar disorder and schizophrenia
  • Intriguingly, the genetic basis of depressive disorder also overlaps with that for obesity and multiple measures of sleep quality, including daytime sleepiness, insomnia and tiredness