Posts Tagged ‘alcohol’

Scientists have revealed a new link between alcohol, heart health and our genes.

The researchers investigated faulty versions of a gene called titin which are carried by one in 100 people or 600,000 people in the UK.

Titin is crucial for maintaining the elasticity of the heart muscle, and faulty versions are linked to a type of heart failure called dilated cardiomyopathy.

Now new research suggests the faulty gene may interact with alcohol to accelerate heart failure in some patients with the gene, even if they only drink moderate amounts of alcohol.

The research was carried out by scientists from Imperial College London, Royal Brompton Hospital, and MRC London Institute of Medical Sciences, and published this week in the latest edition of the Journal of the American College of Cardiology.

The study was supported by the Department of Health and Social Care and the Wellcome Trust through the Health Innovation Challenge Fund.

In the first part of the study, the team analysed 141 patients with a type of heart failure called alcoholic cardiomyopathy (ACM). This condition is triggered by drinking more than 70 units a week (roughly seven bottles of wine) for five years or more. In severe cases the condition can be fatal, or leave patients requiring a heart transplant.

The team found that the faulty titin gene may also play a role in the condition. In the study 13.5 per cent of patients were found to carry the mutation – much higher than the proportion of people who carry them in the general population.

These results suggest this condition is not simply the result of alcohol poisoning, but arises from a genetic predisposition – and that other family members may be at risk too, explained Dr James Ware, study author from the National Heart and Lung Institute at Imperial.

“Our research strongly suggests alcohol and genetics are interacting – and genetic predisposition and alcohol consumption can act together to lead to heart failure. At the moment this condition is assumed to be simply due to too much alcohol. But this research suggests these patients should also be checked for a genetic cause – by asking about a family history and considering testing for a faulty titin gene, as well as other genes linked to heart failure,” he said.

He added that relatives of patients with ACM should receive assessment and heart scans – and in some cases have genetic tests – to see if they unknowingly carry the faulty gene.

In a second part of the study, the researchers investigated whether alcohol may play a role in another type of heart failure called dilated cardiomyopathy (DCM). This condition causes the heart muscle to become stretched and thin, and has a number of causes including viral infections and certain medications. The condition can also be genetic, and around 12 per cent of cases of DCM are thought to be linked to a faulty titin gene.

In the study the team asked 716 patients with dilated cardiomyopathy how much alcohol they consumed.

None of the patients consumed the high-levels of alcohol needed to cause ACM. But the team found that in patients whose DCM was caused by the faulty titin gene, even moderately increased alcohol intake (defined as drinking above the weekly recommended limit of 14 units), affected the heart’s pumping power.

Compared to DCM patients who didn’t consume excess alcohol (and whose condition wasn’t caused by the faulty titin gene), excess alcohol was linked to reduction in heart output of 30 per cent.

More research is now needed to investigate how alcohol may affect people who carry the faulty titin gene, but do not have heart problems, added Dr Paul Barton, study co-author from the National Heart and Lung Institute at Imperial:

“Alcohol and the heart have a complicated relationship. While moderate levels may have benefits for heart health, too much can cause serious cardiac problems. This research suggests that in people with titin-related heart failure, alcohol may worsen the condition.

“An important wider question is also raised by the study: do mutations in titin predispose people to heart failure when exposed to other things that stress the heart, such as cancer drugs or certain viral infections? This is something we are actively seeking to address.”

The research was supported by the Department of Health and Social Care and Wellcome Trust through the Health Innovation Challenge Fund, the Medical Research Council, the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and the British Heart Foundation.

Reference: Ware, J. S., Amor-Salamanca, A., Tayal, U., Govind, R., Serrano, I., Salazar-Mendiguchía, J., … Garcia-Pavia, P. (2018). Genetic Etiology for Alcohol-Induced Cardiac Toxicity. Journal of the American College of Cardiology, 71(20), 2293–2302. https://doi.org/10.1016/j.jacc.2018.03.462

https://www.technologynetworks.com/genomics/news/faulty-gene-leads-to-alcohol-induced-heart-failure-304365?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=63228690&_hsenc=p2ANqtz-9oqDIw3te1NPoj51s94kxnA1ClK8Oiecfela6I4WiITEbm_-SWdmw6pjMTwm2YP24gqSzRaBvUK1kkb2kZEJKPcL5JtQ&_hsmi=63228690

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“Civilization begins with distillation,” said William Faulkner, a writer and drinker. Although our thirst for alcohol dates back to the Stone Age, nobody has figured out a good way to deal with the ensuing hangover after getting drunk.

As a chemical engineering professor and wine enthusiast, I felt I needed to find a solution. As frivolous as this project may sound, it has serious implications. Between 8 and 10 percent of emergency room visits in America are due to acute alcohol poisoning. Alcohol is the leading risk factor for premature deaths and disability among people aged 15-49 and its abuse leads to serious health problems, including cardiovascular and liver cancer. Despite these sobering facts, current treatments for alcohol overdose largely rely on the body’s own enzymes to break down this drug.

I decided to design an antidote that could help people enjoy wine or cocktails or beer without a hangover, and at the same time create a lifesaving therapy to treat intoxication and overdose victims in the ER. I chose to create capsules filled with natural enzymes usually found in liver cells to help the body process the alcohol faster.

Together with professor Cheng Ji, an expert in liver diseases from Keck School of Medicine at the University of Southern California, and my graduate student Duo Xu, we developed an antidote and tested it in mice.

Inspired by the body’s approach for breaking down alcohol, we chose three natural enzymes that convert alcohol into harmless molecules that are then excreted. That might sound simple, because these enzymes were not new, but the tricky part was to figure out a safe, effective way to deliver them to the liver.

To protect the enzymes, we wrapped each of them in a shell, using a material the U.S. Food and Drug Administration had already approved for pills. We then injected these nanocapsules into the veins of drunk mice where they hurtled through the circulatory system, eventually arriving in the liver where they entered the cells and served as mini–reactors to digest alcohol.

We showed that in inebriated mice (which fall asleep much faster than drunk humans), the treatment decreased the blood alcohol level by 45 percent in just four hours compared to mice that didn’t receive any. Meanwhile, the blood concentration of acetaldehyde – a highly toxic compound that is carcinogenic, causes headaches and vomiting, makes people blush after drinking, and is produced during the normal alcohol metabolism – remained extremely low. The animals given the drug woke from their alcohol-induced slumber faster than their untreated counterparts – something all college students would appreciate.

The ability to efficiently break down alcohol quickly should help patients wake up earlier and prevent alcohol poisoning. It should also protect their liver from alcohol–associated stress and damage.

We are currently completing tests to ensure that our nanocapsules are safe and don’t trigger unexpected or dangerous side effects. If our treatments prove effective in animals, we could begin human clinical trials in as early as one year.

This sort of antidote won’t stop people from going too far when consuming alcohol, but it could help them recover quicker.

https://www.technologynetworks.com/neuroscience/articles/a-hangover-pill-tests-on-drunk-mice-show-promise-302970?utm_campaign=NEWSLETTER_TN_Neuroscience_2017&utm_source=hs_email&utm_medium=email&utm_content=63148685&_hsenc=p2ANqtz-_9-CBGC564lH1Jr5Fxrauf8vQZ42sDx9gSSQj_dPJTj3gm3QDvY74R4WiynR1vM5L7tdtTLBIV40iEWBKcEB7JzwFUnQ&_hsmi=63148685

Want to prolong your life expectancy by more than a decade? A new study suggests that you can do just that by following these five healthy habits: never smoke, maintain a healthy body-mass index, keep up moderate to vigorous exercise, don’t drink too much alcohol, and eat a healthy diet.

Adhering to those five lifestyle factors at age 50, compared with not adhering to any of them, was associated with 14 additional years of life expectancy among women and 12.2 additional years among men in the study, published in the journal Circulation on Monday.

Each of those factors is significantly associated with a reduced risk of dying from the top two killers in the United States, cardiovascular disease and cancer, according to the study.
About 610,000 people die of heart disease in the US each year, which is about one in every four deaths, according to the US Centers for Disease Control and Prevention.
About 609,640 Americans are expected to die of cancer this year, according to the American Cancer Society.

“These are some of the leading causes of premature death, so by preventing or reducing the incidence of those diseases, it promotes longevity, and it also improves survival after diagnosis of those diseases,” said Dr. Meir Stampfer, a professor of medicine at Harvard Medical School and professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health, who was a co-author of the study.

“We can do so much better for having a long healthy life by pretty simple minimal changes in our behavior, and only 8% of adults in our country are adhering to these,” he said. “The main take-home message is that there’s huge gains in health and longevity to be had just by simple changes in our behavior pattern, and as a country, I think we need to make it easier for ourselves to do this by promoting tobacco cessation, by providing better environments for physical activity and so on.”

Globally, the US ranks 43rd when it comes to life expectancy at birth, with an average life expectancy of 80, according to 2017 data from the Central Intelligence Agency’s World Factbook.
The three countries ranked highest for life expectancy at birth are Monaco, with 89.4 years; Japan, with 85.3 years; and Singapore, with 85.2 years, according to those data.

The countries with the lowest life expectancy at birth, based on that data, are Chad, with 50.6 years; Guinea-Bissau, with 51 years; and Afghanistan, with 51.7 years.

The ‘surprising’ impact of behaviors on longevity

For the new study, researchers measured the association between those five lifestyle factors and premature death using data from the national Nurses’ Health Study and the Health Professionals Follow-Up Study. The data came from 1980 to 2014 and included more than 122,000 people combined.

Then, the researchers used data from the National Health and Nutrition Examination Surveys to estimate the distribution of those modifiable lifestyle factors among adults in the United States. Those data, from 2013 to 2014, consisted of 2,128 adults, 50 to 80 years old.

The researchers also derived death rates of US adults using the CDC’s Wide-Ranging Online Data for Epidemiologic Research database.

After analyzing the data, the researchers found that, in 2014, the overall projected life expectancy at age 50 was to live 33.3 more years for women and 29.8 more years for men.

Yet among the adults who reported that they adopted all five healthy lifestyle factors, the researchers found, they lived 43.1 more years among women and 37.6 more years among men.

Among those adults who reported that they adhered to none of the five healthy lifestyle factors, the researchers found that they lived only 29 additional years among women and 25.5 additional years among men.

“To me, the surprising outcome was how strong it was: what a big impact these simple behaviors could have on life expectancy,” Stampfer said. “I was surprised that it was that pronounced.”

Among the women, on average, about 30.8% of the life expectancy at age 50 that they gained from adopting five, versus zero, of those lifestyle factors was attributed to a reduced risk of cardiovascular disease death; 21.2% was attributed to a reduced risk of cancer and 48% to other causes of death.

Among the men, those percentages were 34.1% attributed to a reduced risk of cardiovascular disease death, 22.8% attributed to a reduced risk of cancer and 43.1% to other causes.

The study had some limitations, including that the data on adherence to the five lifestyle factors were all self-reported, making outcome vulnerable to measurement errors.

Also, the data analysis did not include measures of certain health conditions that are risk factors for a shorter life expectancy, such as diabetes or high blood pressure.

That limitation, however, “is both a strength and a limitation, in a way … because what we’re estimating here is the prolongation of life expectancy just based on behaviors,” Stampfer said.
“Obviously, it’s much better to do these healthy behaviors from childhood, really, but if you’re beyond age 50, beyond age 60, beyond age 70, it’s not too late,” he added.

The factor that was seen as more ‘powerful’

The findings should encourage and motivate people to adopt a healthier lifestyle, said Dr. Douglas Vaughan, chairman of the department of medicine in Northwestern University’s Feinberg School of Medicine, who was not involved in the study.

Though the study highlighted how the combination of all five lifestyle factors could help prolong life expectancy, Vaughan pointed out how each individual factor also was tied to a reduced risk of premature death.

“It looks like cigarette smoking has a more powerful effect than the other lifestyle changes or behaviors. Certainly, maintaining a reasonable body-mass index is a great way to protect oneself against the development of diabetes,” Vaughan said.

Body-mass index, a calculation derived from a person’s weight and height, is used as a screening tool for body fatness. A normal or healthy body-mass index is typically said to be between 18.5 and 24.9.

“So, in aggregate, we see the effect on longevity, but you can imagine it’s largely through effects on cardiovascular risk and metabolic risk,” Vaughan said. “It suggests potentially at a defined point in life, say age 50, if you adhere to a healthy paradigm like this, you can have an impact on your longevity and on your health span.”

Dr. Jack Der-Sarkissian, a family medicine physician and assistant area medical director of Kaiser Permanente Los Angeles Medical Center, called smoking “the least-debated health risk factor.”

“Beyond cancer risk, smoking contributes to lung disease, heart disease and diabetes. The study shows that even minimal smoking — from one to 14 cigarettes a day — is associated with increased death due to cancer and heart disease,” said Der-Sarkissian, who was not involved in the new study.

As for some of the other lifestyle factors, “getting weight below a BMI of 30 appears to help considerably, according to the study. A higher body weight is linked to increased risk of diabetes and cancer, among other obesity-related conditions,” he said. “The study suggests physical activity of at least 30 minutes a day of moderate or vigorous activities, including brisk walking.”

https://www.cnn.com/2018/04/30/health/life-expectancy-habits-study/index.html

Drinking will shorten your life, according to a study that suggests every glass of wine or pint of beer over the daily recommended limit will cut half an hour from the expected lifespan of a 40-year-old.

Those who think a glass of red wine every evening will help keep the heart healthy will be dismayed. The paper, published in the Lancet medical journal, says five standard 175ml glasses of wine or five pints a week is the upper safe limit – about 100g of alcohol, or 12.5 units in total. More than that raises the risk of stroke, fatal aneurysm (a ruptured artery in the chest), heart failure and death.

The risks for a 40-year-old of drinking over the recommended daily limit were comparable to smoking, said one leading scientist. “Above two units a day, the death rates steadily climb,” said David Spiegelhalter, Winton professor for the public understanding of risk at the University of Cambridge.

“The paper estimates a 40-year-old drinking four units a day above the guidelines [the equivalent of drinking three glasses of wine in a night] has roughly two years’ lower life expectancy, which is around a 20th of their remaining life. This works out at about an hour per day. So it’s as if each unit above guidelines is taking, on average, about 15 minutes of life, about the same as a cigarette.

“Of course, it’s up to individuals whether they think this is worthwhile.”

There is still a small benefit to drinking, which has been much flagged in the past. It does reduce the chance of a non-fatal heart attack. But, said Dr Angela Wood, from the University of Cambridge, lead author of the study, “this must be balanced against the higher risk associated with other serious – and potentially fatal – cardiovascular diseases.”

The big international study supports the new UK recommended limits of a maximum of 14 units a week for both men and women, which were fiercely contested when introduced by England’s chief medical officer, Dame Sally Davies, in 2016. Other countries with higher limits should reduce them, it suggests. They include Italy, Portugal and Spain as well as the US, where for men the recommended limit is almost double.

The study included data from nearly 600,000 current drinkers included in 83 studies carried out in 19 countries. About half the participants reported drinking more than 100g per week, and 8.4% drank more than 350g per week. Early deaths rose when more than 100g per week, which is five to six glasses of wine or pints of beer, was consumed.

A 40-year-old who drank up to twice that amount (100 to 200g) cut their life expectancy by six months. Between 200g and 350g a week, they lost one to two years of life, and those who drank more than 350g a week shortened their lives by four to five years.

Tim Chico, professor of cardiovascular medicine at the University of Sheffield, said smokers lost on average 10 years of life. “However, we think from previous evidence that it is likely that people drinking a lot more than 43 units are likely to lose even more life expectancy, and I would not be surprised if the heaviest drinkers lost as many years of life as a smoker.

“This study makes clear that on balance there are no health benefits from drinking alcohol, which is usually the case when things sound too good to be true.”

Spiegelhalter said it was “a massive and very impressive study. It estimates that, compared to those who only drink a little, people who drink at the current UK guidelines suffer no overall harm in terms of death rates, and have 20% fewer heart attacks.”

Prof Jeremy Pearson, associate medical director at the British Heart Foundation, which part-funded the study, called it “a serious wakeup call for many countries.”

Dr Tony Rao, visiting lecturer in old age psychiatry at King’s College London, said the study “highlights the need to reduce alcohol related harm in baby boomers, an age group currently at highest risk of rising alcohol misuse”. It did not take into account the possibility of mental disorders such as dementia, which could accompany the other health problems drinkers incur.

In a commentary in the Lancet, Profs Jason Connor and Wayne Hall from the University of Queensland Centre for Youth Substance Abuse Research in Australia, anticipated that the suggestion of lowering recommended drinking limits will come up against opposition.

“The drinking levels recommended in this study will no doubt be described as implausible and impracticable by the alcohol industry and other opponents of public health warnings on alcohol. Nonetheless, the findings ought to be widely disseminated and they should provoke informed public and professional debate.”

https://www.theguardian.com/science/2018/apr/12/one-extra-glass-of-wine-will-shorten-your-life-by-30-minutes

Research published in The Lancet Public Health indicated that alcohol use disorder is a major risk factor for dementia, especially early-onset dementia.

“The relationships between alcohol use and cognitive health in general, and dementia in particular, are complex,” Michaël Schwarzinger, MD, of the Translational Health Economics Network, France, and colleagues wrote. “Moderate drinking has been consistently associated with detrimental effects on brain structure, and nearly every review describes methodological problems of underlying studies, such as inconsistent measurement of alcohol use or dementia, or both, and insufficient control of potential confounders. By contrast, heavy drinking seems detrimentally related to dementia risk, whatever the dementia type.”

To determine how alcohol use disorders effect dementia risk, especially among those aged younger than 65 years, researchers conducted a nationwide retrospective cohort of hospitalized adults in France discharged with alcohol-related brain damage, vascular dementia or other dementias between 2008 and 2013. Alcohol use disorder was the primary exposure, and dementia was the main outcome. Using the French National Hospital Discharge database, they studied the prevalence of early-onset dementia and determined whether alcohol use disorders or other risk factors were associated with dementia onset.

In total, 1,109,343 adults discharged from hospital in France were diagnosed with dementia and included in the study. Of those, 35,034 cases of dementia were attributable to alcohol-related brain damage, and 52,625 cases had other alcohol use disorders. Among the 57,353 early-onset dementia cases, 22,338 (38.9%) were attributable to alcohol-related brain damage and 10,115 (17.6%) had an additional diagnosis of alcohol use disorders.

Analysis revealed that alcohol use disorders were linked to a threefold increased risk for all types of dementia and “were the strongest modifiable risk factor for dementia onset” (adjusted HR = 3.34 [95% CI, 3.28–3.41] for women; HR = 3.36 [95% CI, 3.31–3.41] for men). Alcohol use disorders remained associated with an increased risk for vascular and other dementias even after excluding alcohol-related brain damage, according to the findings. Furthermore, chronic heavy drinking was also linked to all other independent risk factors for dementia onset, including tobacco smoking, high blood pressure, diabetes, lower education, depression and hearing loss.

“Our findings suggest that the burden of dementia attributable to alcohol use disorders is much larger than previously thought, suggesting that heavy drinking should be recognized as a major risk factor for all types of dementia,” Schwarzinger said in a press release. “A variety of measures are needed, such as reducing availability, increasing taxation and banning advertising and marketing of alcohol, alongside early detection and treatment of alcohol use disorders.”

Previous research has largely focused on modest alcohol use, and its possible beneficial effect, thus overlooking the effect of heavy alcohol use as a modifiable risk factor for dementia, according to a related comment written by Clive Ballard, MBChB, MRCPsych, and Iain Lang, PhD, of the University of Exeter Medical School, U.K.

“Although many questions remain, several can be answered using existing data, which would provide an opportunity to refine our understanding of the pathways of modifiable risk and develop optimal prevention strategies,” Ballard and Lang wrote. “In our view, this evidence is robust, and we should move forward with clear public health messages about the relationship between both alcohol use disorders and alcohol consumption, respectively, and dementia.” – by Savannah Demko

https://www.healio.com/psychiatry/alzheimers-disease-dementia/news/online/%7B90f5e375-9dd3-4715-9206-7c148d563d80%7D/heavy-drinking-may-increase-risk-for-dementia?utm_source=selligent&utm_medium=email&utm_campaign=psychiatry%20news&m_bt=1162769038120


Kent Hutchinson of the CU Change Lab is one of authors of this new research on the effects of Marijuana on the brain.

by Cay Leytham-Powell

Marijuana may not be as damaging to the brain as previously thought, according to new research from the University of Colorado Boulder and the CU Change Lab.

The research, which was published in the journal Addiction, examined the brains of more than 1,000 participants of varying ages, and found that long-term alcohol use is much more damaging to the brain than marijuana, contradicting years of research into the effects of marijuana and other cannabinoid products on the brain.

These findings, and other conclusions suggesting the potential public health benefits of marijuana, come amid the recent back-and-forth on federal marijuana policy and the nation’s opioid crisis.

Yet scientists are still hesitant to say that cannabinoid usage, specifically as it pertains to marijuana and its associated products, is beneficial.

“Particularly with marijuana use, there is still so much that we don’t know about how it impacts the brain,” said Rachel Thayer, a graduate student in clinical psychology at CU Boulder and the lead author of the study. “Research is still very limited in terms of whether marijuana use is harmful, or beneficial, to the brain.”

While the negative effects of alcohol on the brain have been known by researchers for years, it has been assumed that cannabinoids are as damaging to long-term brain health—if not more—given the immediate psychoactive effects of the THC (the chemical that gets a person high) in marijuana.

However, this may not necessarily be true.

“When you look at the research much more closely, you see that a lot of it is probably not accurate,” said study co-author Kent Hutchison, a professor of behavioral neuroscience at CU Boulder and co-director of the CU Change Lab, which explores the factors linked with health and risk behavior.

“When you look at these studies going back years, you see that one study will report that marijuana use is related to a reduction in the volume of the hippocampus. The next study then comes around, and they say that marijuana use is related to changes in the cerebellum or the whatever.”

“The point is that there’s no consistency across all of these studies in terms of the actual brain structures.”

To combat this misconception in the existing literature, the researchers gave a fresh look at some existing neurological imaging data from the MRIs of both adolescents and adults to see how, using the same variables and controls, the influence of cannabinoids on the brain compared to or contrasted with alcohol.
“With alcohol, we’ve known it’s bad for the brain for decades,” said Hutchison. “But for cannabis, we know so little.”

To see any potential difference, the researchers used the data to examine the most important neurological components: gray matter and white matter.

Gray and white matter are the two main types of tissue that make up the brain and central nervous system. Gray matter is the “stuff”—the cell bodies, dendrites and axon terminals—that enable functionality. White matter, then, is how the grey matter communicates between clusters. Any loss of size or integrity in either can make the brain not work quite like it should.

The study found that alcohol use was significantly associated with a decrease in gray matter size and white matter integrity, particularly for adults who may have decades of exposure. Marijuana and associated cannabinoid products, on the other hand, were not shown to have any long-term impact on the amount of gray matter in the brain or on the integrity of the white matter.

The research demonstrated that, “while marijuana may also have some negative consequences, it definitely is nowhere near the negative consequences of alcohol,” according to Hutchison.

Despite marijuana not being as harmful as once thought, and definitely not as damaging as other legal and illegal products, the research has not yet proved any possible benefits. This is particularly the case as it relates to the different products on the market (both THC and non-THC-containing cannabinoid products), their usage with pain and addiction treatment and the effect on different ages — especially as cannabinoid usage is on the rise among older populations.

“Considering how much is happening in the real world with the legalization movement, we still have a lot of work to do,” Hutchison said.

https://www.colorado.edu/asmagazine/2018/02/02/cannabinoids-are-easier-brain-booze-study-finds

by Tori Rodriguez, MA, LPC

Individuals with major depressive disorder (MDD) have double the risk of alcohol use disorders (AUDs) and vice versa, and it has previously been proposed that some people with MDD may use alcohol to self-medicate. Though alcohol can become depressant if used chronically, alcohol initially has an antidepressant effect, though the underlying mechanisms have not been identified. Findings reported in September 2016 in Nature Communications begin to elucidate the basis of this action.

Behavioral and molecular evidence of the rapid antidepressant activity of NMDA receptor (NMDAR) antagonists, which have been found to be effective within 2 hours of administration and remain so for 2 weeks, represents a significant advance in depression treatment. Antidepressant efficacy involves the induction phase and the sustained phase.

The sustained phase of rapid antidepressants requires “both new protein synthesis and an increase in protein stability… for the GABABR shift in function necessary to increase” the activity of mTORC1, a mechanistic target of rapamycin complex 1, the authors explained in their paper. Rapamycin (mTOR) is a “serine/threonine kinase essential for messenger RNA translation” and is required for the sustained impact of rapid antidepressants.

Citing previous findings that ethanol (EtOH) also blocks NMDARs in the hippocampus, scientists at the University of Texas at Austin and Wake Forest University School of Medicine in Winston-Salem, North Carolina, aimed to determine whether EtOH and NMDAR antagonists exert rapid antidepressant effects via the same synaptic pathways in rodents. They hypothesized that EtOH “has lasting antidepressant efficacy, shares the same downstream molecular signaling events as rapid antidepressants, and requires de novo protein synthesis.”

First, they found that acute exposure to EtOH led to antidepressant and anxiolytic behaviors in rodents for up to 24 hours. They then discovered that, like NMDAR antagonists, EtOH alters the expression and signaling of GABABR, increases dendritic calcium, and leads to the synthesis of new GABABRs. This synthesis requires fragile-X mental retardation protein (FMRP), an RNA-binding protein of which precise levels are needed for normal neuronal functioning.

The antidepressant effects and the changes in GABABR expression and dendritic calcium were not observed in in Fmr1-knockout (KO) mice, supporting the concept that FMRP has in important role in regulating protein synthesis after EtOH exposure, and thereby facilitating its antidepressant efficacy.

These results point to a shared molecular pathway for the antidepressant activity of EtOH and rapid antidepressants, and highlight a mechanism involved in the initial antidepressant action of alcohol. “A shift in GABABR signaling is observed with both rapid antidepressants and acute EtOH treatment, which may provide insight into the molecular basis for the high comorbidity between major depressive disorder and AUD,” the authors concluded.

http://www.psychiatryadvisor.com/addiction/rapid-antidepressant-effect-of-alcohol/article/567335/?DCMP=EMC-PA_Update_RD&cpn=psych_md%2cpsych_all&hmSubId=&NID=1710903786&dl=0&spMailingID=15723696&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=881842067&spReportId=ODgxODQyMDY3S0