Are some people genetically predisposed to alcohol use disorder?

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How much alcohol is too much?

And what makes some people more likely to suffer? alcohol use disorderothers less?

These questions have been at the top of the concerns of researchers who study the effects of alcohol on the human body. One of these is Henry Kranzler, MD, professor of psychiatry and director of the Center for Addiction Studies at the University of Pennsylvania’s Perelman School of Medicine.

For more than 20 years, his work has focused on the genes of substance dependence and whether precision medicine – medicine that targets the individual genetic makeup—Can help treat addiction.

His work has won numerous awards, so he’s only joking in part when he points out that recent research by his group has received the ultimate acknowledgment: a study suggesting alcohol use ages and shrinks the brain that was the subject of a weekend’s update on “Saturday Night Live.” .

I was one of the researchers on a recent study that found that moderate alcohol intake — a few beers or glasses of wine a week — may have risks to the brain. What are those risks?

We found that drinking more than one drink per day was associated with reductions in brain sizewhich can have cognitive effects.

I should point out that this was a correlational study, which means we can’t prove that alcohol caused the effect. And it was syllabary, which means it was a snapshot in time. Therefore, we also don’t know if these changes occur in direct response to changes in drinking, including whether they improve when people stop drinking.

But specifically, we found that drinking an average of one drink per day was associated with lower Gray matter or unclear Volume and decreased white matter volume.

This is important because the gray matter is the part of the brain that contains the brain cell bodies, which regulate neural activity. This is where we think. White matter is an extension of these brain cells and allows brain regions to communicate with each other. Both gray and white matter are important for all the cognitive processes we can perform.

In addition to volume reductions, we have seen that safety white mattertheir regulation, is further disrupted as the level of drinking increased.

All of this suggests – but we didn’t measure it – that these effects are associated with poorer cognitive function. We say that alcohol ages the brain because its effects are similar to those of aging. The older we get, the cognitively slower we become.

So, should government guidelines on safe drinking need to be updated?

yes. Currently, the National Institute on Alcohol Abuse and Addiction in Women recommends that women drink no more than seven glasses per week on average, and men no more than 14.

There is other evidence that seven drinks for both sexes is an important threshold, although it may be six or eight. For public health purposes, it would be good to know. But with this study, I reduced my alcohol consumption, which is probably the best indicator of the strength of my beliefs.

What has your research revealed about the genes for alcoholism? Are you more likely to develop alcohol use disorder if someone close to you has it?

The simple answer is yes.

and more family members— in addition to being more closely related to parents or siblings than to cousins ​​— the higher the risk.

This was known before the current era of molecular genetics. It was based on the results of family history and genetic epidemiology. These studies evaluated people and their diagnoses and used mathematical models to determine risk.

Over the past 20 years, since the sequencing of the human genome, this has been demonstrated. We are beginning to identify the specific variations in DNA that are responsible for the risks. And the number of differences that we know is increasing.

We don’t know exactly how many we’ll find, eventually, but we do know that alcohol use disorder is highly polygenic—it involves many different genes.

A person’s height, which is also polygenic, is influenced by about 11,000 genes. Alcohol use disorder may be in the field. Everyone has these genes. But there are many forms of the gene.

What differs between people is their variables.

In general, the more risk variables you have, and the fewer protective variables, the more likely you are to develop an alcohol use disorder.

Does learning more about the genetic component of alcohol use disorder pave the way for personalized treatment?

We’re not at the stage where we can do that yet. But we are getting close. By looking at common variants across a person’s entire genome, we can do this.

Theoretically, if you performed a genetic makeup of a large sample of people with alcohol use disorder, you could use the information to calculate a single risk score, which could be used to determine who would benefit from a particular type of medication to treat the disorder.

One medication I’ve been studying for a while is called topiramate, which is an antispasmodic drug that may reduce cravings and excessive drinking.

We initially thought that a single genotype predicted response to topiramate treatment. But we found out that it’s more complicated than that. So we have now turned to these degrees of risk.

They are used in other cases – for the diagnosis of breast cancer, cardiovascular diseases. They are not yet used for psychiatric conditions, including substance use disorders, but I believe they will be. It is a matter of time and investment to collect large and diverse samples on which to build calculations.

It holds great promise, and there are a growing number of biobanks that make this type of research possible. For example, the UK Biobank includes 500,000 genotyped individuals. They are now obtaining MRI data from 100,000 of these individuals.

In the United States, the Million Veteran Program is recruiting two million veterans to give a blood sample from which DNA can be extracted and analyzed. Veterans also fill out questionnaires and give access to their own Electronic health recordsExtensive Veterans Administration version.

This has been very helpful for us in doing studies to determine the relationship between a trait, such as alcohol use disorder, and the genes that contribute to it.

Given this genetic component, is there a way to pre-screen people to see if they are susceptible to alcohol use clutter?

Yes, and that’s exactly what I was getting with my polygenic risk scores. These have been used successfully to divide groups into higher or lower risk levels. However, it is not yet sufficiently developed to account for the individual risk of mental disorders for use in the context of prevention or treatment.

Expectations are still crude. We still need more information. We need larger and more diverse samples on which to base the calculations for these scores.


More alcohol, less brain: Study finds association starting with an average of just one drink a day


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