Chronotypes: Sleep, Addiction, and More

In the modern age one will often be bombarded by health tabloids with snappy titles attempting to sell you on their new diet, supplement, or lifestyle when looking for health advice. They often expound a new diet that is proven by SCIENTISTS to be ideal for sleep, lifestyle, and weight loss(compared to the other ones that are also proven to be ideal by the ever-pervasive scientists). Among this buzz of marketing it can often be difficult to get any concrete info on what's best for oneself, which is why we need to look to genetics. 

Examples of some chronotype categories

Chronotypes are a term utilised by sleep scientists to categorise individuals based on inborne preferences related to their internal clock/circadian rhythms. This genetic predisposition can be positively correlated with a variety of interesting things that one may be believe are simply lifestyle-related. Things like preferring late nights or mornings for work, risk for video game or internet addiction, and even appetite have been positively correlated to chronotypes. Being more of a "neutral" chronotype, as in following the sun more or less, is correlated with less risk of obesity, normal metabolism, and less risk for addiction. On the contrary, a more "extreme" chronotype, those being extreme night owls or early risers, are more at risk for sleep-related illness, addiction, and potentially more. Overall, if one is concerned about their health it may be worth looking into chronotype studies to figure out how their genetics may be affecting their day to day. 

Sources: 

https://www.yahoo.com/lifestyle/best-time-wake-day-genetics-194209285.html?guccounter=1

https://www.sleepfoundation.org/how-sleep-works/chronotypes

https://www.sciencedirect.com/topics/psychology/chronotype#:~:text=Chronotype%20refers%20to%20the%20endogenous,to%20personality%20and%20lifestyle%20aspects.

GWAS Shows Correlation of Cannabis Use Disorder with Lung Cancer

 The Genetic Basis of Cannabis Use Disorder and Lung Cancer

    A recent GWAS from Nature shows a correlation between lung cancer susceptibility and cannabis use disorder. This study was a meta-analysis between nearly 1 million individuals of European, African, mixed American, and East Asian ancestries and it examined single nucleotide polymorphism (SNP) heritability. Using this data, the researchers found that 22 loci were associated with the susceptibility of lung cancer, but in each group, the expression of the SNPs was different. For instance, the East Asian sample group's SNPs were intronic to the semaphorin 6D-encoding gene, whereas the American group was an intergenic region downstream of leucine-rich repeats containing the semaphorin 6D-encoding gene. They used a comparative analysis of psychiatric symptoms and found many overlapping associations between cannabis use disorder and the likelihood of developing lung cancer. This association comes from a likelihood of becoming a smoker and resorting to cigarettes, which would most likely, in turn, result in a greater risk for lung cancer in those populations.

    I found this study to be very interesting and it definitely shines some light on the addictive manner of cannabis and cannabis-containing products. The biological mechanism of cannabis and the cannabinoids involved are still not fully known, which I think is a long-term danger in regards to smoking/consuming cannabis products. Furthermore, those with cannabis use disorder being at a greater likelihood for developing lung cancer is scary to think about and could considerably be an element of medicine/psychiatry to dig deeper to in the meantime. Nevertheless, going forward I think we should be more conscientious of what we are breathing in and consuming, because with lung cancer being the top cause of death, that should be enough to scare us into treating our bodies better. 

Links:

1. https://www.nature.com/articles/s41588-023-01563-z 

2. https://www.news-medical.net/news/20231123/Genome-study-unveils-genetic-ties-between-cannabis-use-disorder-and-lung-cancer-risk.aspx 

Cannabis: Who's More Susceptible to Health Risks?

 Over the past few decades, Cannabis has not only been legalized medically in certain places in the U.S. and other countries but also for recreational use as well. As shown in the article, it can alleviate the negative effects of certain conditions (such as chronic pain and cancer). Even with the benefits associated with the drug, there are also risks that come with taking it as well. This consists of increased risks of mental disorders and cancer (specifically lung cancer). According to a new study, people with certain genes will have an increased likelihood of becoming addicted to cannabis (One-third of users become addicted) along with the health risks stated previously. 

  Cannabis is a drug that's important to many people throughout the world with, for some, it being a major part of their lives. Yet, I never knew about the actual risks that the drug that could come with the use of this drug for certain people. It seemed obvious that lung cancer would be a possible risk but I didn't think the same for mental disorders. As stated by Joel Gelernter (co-author of the study) in the article, researchers will need to continue building on top of this data to understand the risks better. One day, there will be a way to determine who is best suited to be prescribed cannabis.

Links

-      https://www.nature.com/articles/d41586-023-03629-8

-      https://www.nature.com/articles/s41588-023-01563-z

Addiction Impacted by Genetics

 Alcoholism is a genetic addiction that accounts for 40-60% of the risk. Opiate and cocaine addictions also have comparable heritability rates. Addiction susceptibility is linked to large chromosomal areas, although genetic variations are unknown. Alcohol sensitivity and acute alcohol side effects are increased in some East Asian groups due to enzyme polymorphisms that metabolize alcohol. Aldehyde dehydrogenase type2 homozygotes seldom develop alcoholism. Drug misuse affects inbred mice and rats differently. Identification of mouse lines carefully bred for alcohol or drug responsiveness should illuminate addiction pathways. Due to the intricacy of addiction and the possibility of variations in distinct genes causing addiction in different lineages, identifying genes that increase addiction risk is complex. Poverty, criminality, and delinquency impact risk, but their effects are unclear. Stress and genotype can also affect an animal's sensitivity to a substance of abuse, according to animal research. Investigating how genetic variants and environmental variables interact is crucial. Genetic and ecological variables impact an individual's initial drug sensitivity and how nerve cells and circuits adapt to prolonged drug exposure, which leads to addiction. Behavioral research emphasizes quantifying behavioral endpoints with the same complexity and interassay reliability as non-behavioral variables. Genes may modify the form or function of specific brain circuits throughout development or maturity or influence neural circuits influenced by environmental inputs, making them vulnerable to addiction. Genetic techniques and particular phenotypes may help identify addiction susceptibility genes in people and animals.

Animal models are absolutely necessary for elucidating the neurological workings of the addictive process. Nevertheless, genetic changes can occasionally result in traits for which there is no obvious explanation. It is now conceivable because of the growing sophistication of genetic techniques and the predictive value of animal models, to grasp the cellular mechanisms and neuronal circuitry linking chemical events with complicated behavior. This will allow for the completion of the puzzle, which was previously impossible.

Addiction is a broad term that incorporates a variety of maladaptive behaviors. These behaviors include use disorders for substances like alcohol, nicotine, cannabis, and cocaine, all of which significantly contribute to morbidity and death. In this overview, categorization, diagnosis, heritable variation, gene-based techniques, alternative genetic variations, gene-environment interactions, and pharmacogenomics are discussed. In addition to this, it explores how these methodologies might be applied to better understand the mechanisms that are at the root of nicotine addiction and to develop novel therapies.

https://www.nature.com/articles/ng1100_277 

https://www.nature.com/articles/tp201254 

Genetic Variants and Addiction

Recent research has shown significant changes in our understanding of how addictions develop in humans. Individuals with a genetic variant for a neurotransmitter gene are at an increased risk of addiction to alcohol and other substances if exposed to stressors early in childhood. 

Researchers at the University of Oklahoma College of Medicine I've been working with the National Institute of Alcohol Abuse and Alcoholism to understand the correlation between genes and addictions. They focused on the variant for the gene that gives rise to the enzyme catechol-o-methyltransferase (COMT). This enzyme manages various neurotransmitters, including dopamine, within the body. Individuals in the study ranged from ages 18-30 years old with a history of adversity in early childhood. These individuals showed lower activity for the COMT variant, leaving them more vulnerable to consuming alcohol and other substances. 

This study was fascinating for two main reasons. It establishes the relationship between our genetics and how it can expose us to different medical conditions later in life. Furthermore, this study shows how the environment plays a role in activating genes or causing variances due to stressors present early in life. 

The Epigenetics of Addiction and Depression

     

    Dopamine controlling genes may be a root cause of addiction to drugs like alcohol and cocaine, as well as an answer to why drugs for depression need to be taken for weeks before they have an effect, according to the article The Epigenetic Secrets Behind Dopamine, Drug Addiction and Depression, by R. Douglas Fields.

    Neurotransmitters may have more to do with this process than we realized. Neurotransmitters transmit signals between neurons, which allows us to think, learn, and feel. When neurotransmitter signals misfire, we suffer problems with thinking, making decisions, or mood disorders, like depression or bipolar disorder. Serotonin, a kind of neurotransmitter known as a monoamine, helps to regulate moods and to treat depression, drugs that increase the level of serotonin in the brain are usually prescribed. According to research led by Ian Maze done last year, serotonin has another function: it can be used as one of the special markers of DNA. Specifically, serotonin bonds to a histone, the protein used as a spool, known as H3. H3 controls the genes that turn human stem cells into serotonin neurons. Maze’s team figured that if serotonin had this function, there was a chance that dopamine could also do the same thing, with the genes that control drug addiction. After all, the same enzyme that bonds serotonin to H3 also allows dopamine to be attached to H3, in a process called dopaminylation. This discovery may be essential for future research into addiction, or even broader, other kinds of mental illness, and how to treat these disorders. I already knew that genetics affected disorders and diseases like these, but it is also very interesting to look at how epigenetics plays a role.

Additional Links

https://www.psychologytoday.com/us/blog/integrative-mental-health-care/201912/epigenetic-influences-addiction

Your Gene Affect Your Chances of Starting and/or Quitting Smoking

                             

A genetic study done by Ke Xu and Boyang Li revealed that there are 99 genetic variants that are linked to the start of a smoking addiction and 19 variants that are linked to being able to quit smoking. The study was done of a wide variety of individuals from different backgrounds, and it was done over a long period of time so the researchers could get longitudinal data on the smoking history of the patients. The likelihood of smoking is not entirely genetic, environmental factors also play a role in this trait. About 40-50% of the likelihood of smoking is genetic while the rest is environmental. Xu states that the smoking has decreased  by education of policies that raised taxes of tobacco products and limited the sales and advertisement of those products. Also the development of smoking limited zones played a role in decreasing the likelihood of people developing a smoking addiction. The findings of the research are not yet certain, they believe that these genetics variations may only be loosely connected to the patient's smoking behavior, but regardless I think this is a step forward in being able to find a cure for an addiction to smoking. By finding out that genes are involved in addiction can lead to more studies being done for this topic. Once they discover how the decision-making aspects of a smoker's brain is different from an average person's brain, treatments could be developed to help with that. This can also apply to other types of addiction and more people can be alleviated of their disease. 

https://yaledailynews.com/blog/2020/11/05/smoking-and-quitting-may-be-genetic-new-research-indicates/ 

A Genetic Linkage to Alcohol Withdrawal Symptoms

 

   It has previously been established that there is a genetic linkage between our genes and the tendency to consume alcohol, but in this genome-wide study, researchers have linked genetics to the severity of alcohol withdrawal symptoms. This is a relevant research area given that nearly 16 million Americans are affected by some kind of alcohol disorder. Alcohol acts as a depressant to our central nervous system, and when an addiction is formed our brain gets used to constantly working harder to be more alert. Many people that try to break their alcohol addiction suffer from withdrawal symptoms, such as anxiety, shaky hands, nausea, and vomiting. Previously it was thought that the level of drinking and the duration of the addiction were large factors on the severity of the withdrawal symptoms, but this study now reveals a genetic link to the severity of withdrawal symptoms.

     The study was a genome-wide association study, which analyzes complete DNA sets across various populations. Specifically, the study found that variations in SORCS2 gene were highly linked to severity of alcohol withdrawal symptoms. The reasoning behind this is that variations in the SORCS2 disrupt stress-related mechanisms in the hippocampus of the brain. This means when this variation is active, the central nervous system is hindered and unable to adjust to the sudden cessation of alcohol intake. Another interesting finding from the study was that those of African-American heritage do not appear to carry the gene variant, whereas as many as 1 in 10 Americans of European descent carries the variation in this gene.

     As unfortunate as it is, alcoholism is a very prevalent problem in our society that often becomes worse over time and sometimes is left untreated due to the social acceptance of drinking in public places. It is promising to see some research going into an area that could potentially improve the treatment of those suffering from an alcohol-related disease. It is also curious to wonder whether this same gene has any effect on the severity of withdrawal symptoms from other drug addictions to depressants, or if it solely specific to withdrawal from alcohol. I am also curious about the correlation they found between race and the ability to having this variation in the gene. As with any genetic linkage, this also opens the possibility for new genetic-based therapies and the hope that possibly using personalized therapies based on genetics can vastly improve the symptoms of alcohol withdrawal.

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Why genetics makes some people more vulnerable to opioid addiction – and protects others

Genetics can influence a person’s risk for heart disease, cancer or diabetes, and it can also make them more or less susceptible to addiction. There has been a lot of research conducted in the last decade that focused on tiny differences in a person’s DNA - termed single-nucleotide polymorphisms or SNPs. SNPs can indicate whether you have a higher or lower risk for addiction. For example, the thing that helps against drug dependence (specifically opioid dependence) is a single building block change in the opioid receptor gene. On the other hand, variations and mutations in genes for three different dopamine receptors have been linked to increased risk for opioid addiction.

It's also your parents and grandparents who influence whether you are more or less susceptible since you are getting your genetics from them. For example, if you have a dopamine receptor SNP that makes you more likely to develop an addiction, there's always the chance that that gene is "read” differently by your body’s cells due to epigenetic changes. If that's the case, then that risk may not impact your life.

Rates of abuse of opioids have gone up over the past 15 years and continue to climb. The continuation of this research could one day help to achieve preventative measures and treatments that not only help those currently struggling with substance abuse but protect future generations.


Article: http://theconversation.com/why-genetics-makes-some-people-more-vulnerable-to-opioid-addiction-and-protects-others-92000 

Genes Linked to Addiction

   

    Studies have been done to discover the linkage of genetics and addiction. With the opioid epidemic striking the population, this topic has been a cause of interest for many people. The gentic  information in our cells influence the way our brains function and our physical responses to chemicals within our bodies. Therefore, it is apparent that some people become addicted to drugs based off of the way they respond to the chemicals they are exposed to. The Human Genome Project allowed scientists to study the entire genetic make up of humans and figure out how they can use genetics to compete with addiction. There are limitations to this experiment, however researchers are working on a discovery to help those who suffer from addiction. Researchers are also studying the family linkage of drug abuse. While studying this linkage, they have found genetic markers that may trigger addiction, but have also found the same genetic markers in family members who are not addicted to drugs.
     According to the National Institute on Drug Abuse, genetic information only accounts for half of a person's vulnerability. Other factors include age when a person starts using mind altering substances, neighborhood, availability, presence of mental health issues, and gender. Addiction genes need a trigger from the environment to be activated.
     I believe this is a topic that should be further studied to figure out a better way to treat those who suffer from drug abuse. I personally believe it is a disease that should be treated like one and many people are dying from this disease. It is an extremely hard subject to find a definite solution to, however, we can keep trying.

www.addictionandrecovery.org
https://thecanyonmalibu.com/drug-addiction/genetics

The Genetics and Epigenetics of Addiction

Addiction is a topic that has become familiar to the citizens of the United States. But why do some become addicted to substances while others do not? Family studies that have been conducted suggest that as much as half of a person's risk of becoming addicted depend on their genetic makeup. Research on the human genome has shown that, on average, the DNA sequences of any two people are 99.9 percent the same. However, that 0.1 percent variation is profoundly important—it’s still 3 million. These differences contribute to visible variations, like height and hair color, and invisible traits, such as increased risk for or protection from certain diseases such as heart attack, stroke, diabetes, and addiction. By pinning down the biological basis of this risk scientists would be able to combat the problem of addiction. Epigenetics is the study of functional, and sometimes inherited, changes in the regulation of gene activity and expression that are not dependent on gene sequence (Chadwick 317-324).  These epigenetic marks can affect health and even the expression of the traits passed to children. For example, when a person uses cocaine, it can mark the DNA, increasing the production of proteins common in addiction. Increased levels of these altered proteins correspond with drug-seeking behaviors in animals. "Histones, as another example, are like protein spools that provide an organizational structure for genes. Genes coil around histones, tightening or loosening to control gene expression. Drug exposure can affect specific histones, modifying gene expression in localized brain regions. Science has shown that manipulation of histone-modifying enzymes and binding proteins may have promise in treating substance use disorders" (Heller, Cates, Pena 1720-1727). The division of Neuroscience and Behavior at the NIDA's genetics research program is currently researching the genetics and epigenetics controlling addiction which hopefully will provide better ways to combat it. 

 This article was incredibly interesting, being someone who studies science and has struggled with addiction in the past, I found the article and the research being done promising. Having a family history of addiction is common among addicts (including me) I meet and individuals I talk to, which has always lead me to believe there is a genetic link to addiction; hopefully this research sheds light on the causes of addiction and helps individuals not go through the things that addicts in the past have had to go through.

1. Heller EA, Cates HM, Peña CJ, et al. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci. 2014;17(12):1720-1727.
2. Chadwick LH. The NIH Roadmap Epigenomics Program data resource. Epigenomics.2012;4(3):317-324

https://www.drugabuse.gov/publications/drugfacts/genetics-epigenetics-addiction
https://www.drugabuse.gov/about-nida/organization/divisions/division-basic-neuroscience-behavioral-research-dbnbr/genetics-molecular-neurobiology-research-branch-gmnrb

Changes of the Brain Causing the Drive of Alcohol Dependence

Alcoholism is a dangerous addiction in which neurotransmitters are the pathways of addiction. Each person is different and handle the affects differently.

Recently, scientists at The Scripps Research Institute conducted a study in alcoholism that could possibly help develop personalized treatments for individuals. Both alcohol-dependent and nondependent rats were used to show the main difference in their brains when given alcohol. It was shown that when given alcohol, there was increase in activity in the central amygdala. According to their studies, the activity was due to two separate signaling pathways in the brains. In nondependent rats, their brain activity increased L-type voltage-gated calcium channels (LTCCs) which boosted the release of GABA, a neurotransmitter, and when blocked, it reduced voluntary alcohol consumption. In the alcohol dependent rats, it was the opposite and there was a decrease in LTCCs. They researchers had found that a stress hormone (CRF) and its type 1 receptor (CRF1) drove the increase of activity and by blocking the CRF1s, voluntary alcohol consumption had decreased.

This could help researchers in developing more personalized treatments to those who have problems with alcoholism by seeing how the individual’s brain react to the different therapeutics. I think this would be great for those who seek out help if they have an alcohol problem. It would make it less stressful to go through therapy knowing what happens to the brain and how it could be addressed.

Scripps Research Institute. "Surprising brain change appears to drive alcohol dependence." ScienceDaily. ScienceDaily, 12 April 2017.

<www.sciencedaily.com/releases/2017/04/170412132352.htm>.

https://pubs.niaaa.nih.gove/pulications/aa77/aa77.htm 

Genetic Link to Addiction

Researches have noticed that people who clear nicotine slower are twice as likely to become addicted. The study focused on genetic defects that have a moderate or sever affects on the liver's ability to metabolize nicotine. 281 seventh graders that have begun to smoke, but not are not necessarily addicted were studied and thirteen percent had versions of the defected gene. Also having the nicotine remain in the brain longer also sped up the addiction.

It would be interesting to see how well this study develops. It could help save lives of many Americans from having to rely on such an addictive drug that is so readily available and is harming so many. Having a better understanding of how toxins affect us and how are body react to them can all be discovered through genetics.

Who Gets Hooked On Drugs?

A rat study done at the University of Michigan found genetic markers that influence addiction. 

People may ask why some people get addicted to cocaine after one try, while others will try it and be able to leave it alone. You may ask why some people are able to stay clean after rehab while others relapse. These questions may have a lot to do with the genetic factors that vary from person to person. Of course, we know that animal factors cannot explain all of the factors that lead to differences in addictions in human bodies, but the findings revealed information about the roles played by both inherited traits and addiction related changes in the brain.

The researches looked in rats' brains for the genetic instructions needed to make a key "pleasure receptor" called D2. It allows brain cells to receive signals sent by the brain chemical dopamine, or cocaine. They found that more addiction-prone rats had lower levels of D2 instructions to begin with when compared to the other rats, in an area of the brain known to play a major role in addiction.

The addiction-prone rats also were more likely to carry a specific mark on their DNA called an epigenetic tag. This tag called H3K9me3 kept their brain cells from reading the gene for D2 receptors, but after they became hooked on cocaine, the addiction-prone rats had the same levels of D2 as the less addiction-prone ones. When the cocaine was taken away for a while these rats were more likely to relapse to addictive behavior if they had started out with the epigenetic tag that kept their cells from reading the D2 gene.

I have always asked the question why people get addicted to drugs and others do not, but I have never thought it was a genetic factor in the brain. I always thought it was how you were raised or what influences from your environment affected you. I never thought to assume it was a genetic issue.

Maybe a "Quit Smoking" Gene

Do you smoke still? Have you ever tried to break the habit? Whatever the case, you are not alone in the struggle. 

Scientists throughout the world, specially Ming Li and the research team in Virginia, have conducted experiments between 1994-2014 to assess possible genetic influences on smokers. 22 different studies were performed with over 9, 500 smokers involved, and the results were revolutionary. These scientists specifically targeted a Taq1A sequence of DNA in the human genome.  Smokers with the A2/A2 variation of this DNA sequence found it easier to quit smoking--the "cold turkey" and instantaneous quitters. Smokers with other variation of the Taq1A gene found it very difficult to quit, often committing and getting hooked back to the habit. The sequences of DNA influence the amount of dopamine being produced in the brain in response to the nicotine levels in blood. Consequently, the A2/A2 individuals release less dopamine, making nicotine less addictive; therefore, it becomes easier to quit. 

I found this research very interesting. I have always wondered why some individuals can quit smoking seemingly much easier than others. Professor Edelmen, a professor of medicine in New York, states, "There's a huge variability in the ability to quit smoking…" Although this is true, geneticists have discovered a genetic influence on smokers that makes sense biologically. 

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Scientists Spot Gene Linked to Tanning ‘Addiction’

A recent study suggests that people who carry a particular gene variant may be more likely to develop an addiction to tanning. Whether from the sun or from a tanning bed, the idea that ultraviolet light can be addictive is still fairly new, although the recent studies are presenting biological evidence that some people can and do develop a dependence on ultraviolet radiation, similar to the way that some people become dependent on drugs. A researcher at the Yale School of Public Health, Brenda Cartmel, stated that “It’s probably a very small percentage of people who tan that become dependent,” but to develop refined therapies understand why some people become dependent is important. Unfortunately due to indoor tanning, people getting skin cancer are at younger and younger ages. 

Given that ultimately what they want to do is prevent skin cancer, the team of researchers wanted to see if there are any gene variants connected to tanning dependence, since genes are known to sway the risk of addiction. Saliva samples were taken from 79 people that showed signs of tanning dependence and from 213 people who tanned but showed no signs of being addicted at all. From the two different groups, over 300,000 gene variations, there was one gene that noticeably stuck out called PTCHD2. This gene’s exact job is not known for sure but it does generally act in the brain. For the reason that the biology behind tanning dependence and its possible consequences are so important, the research will keep continuing. 

In a recent study it was found that exposing mice to a daily dose of ultraviolet light boosted the blood levels of beta-endorphins. Beta-endorphins are substances created by the pituitary gland and function specifically as neurotransmitters between nerve cells. Beta-endorphins have drug-like qualities creating multiple effects. Response to pain is an example. In addition to response to pain, beta-endorphins are released during periods of intense excitement; capable of enhancing moods and fostering feelings of relaxation. These are the “feel-good” hormones and act on the same pathways in the brain as opiate drugs, like heroine and morphine.

For this particular study, these hormones ultimately suggest that the UV exposure is rewarding to the brain because the sunlight triggers the skin to synthesize vitamin D and eventually the brain evolved to find the UV exposure rewarding. Developing a dependence on tanning or more specifically UV light may seem in a way ridiculous but the potential consequences can be devastating. As a person who loves the beach and loves the sun and also used to love indoor tanning, I found this article extremely interesting.

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