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can genetic tweaks combat anxiety? new study suggests it’s possible

scientific flukes can change the course of health history, and a new accidental discovery regarding anxiety and your genetics is on the road to doing just that.

by angelica bottaro

apr 1 2024

10 minute read

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modern living can drive changes on a cellular level that contribute to anxiety risk and development. getty images

scientific flukes have changed the course of history when it comes to healthcare. for example, dr. alexander fleming’s discovery of penicillin was purely an accident, but it led to the invention of the antibiotic that would go on to save many lives.

now, a group of medical researchers, led by professor alasdair mackenzie of aberdeen university in the north of scotland, performing a study on genes and genetic differences associated with obesity and addiction, have made their own happy accident discovery in the way of gene enhancers, which are essentially on/off switches in genetics.

this time, the unplanned scientific breakthrough could change the way medical professionals understand and approach anxiety and, if all goes well in their upcoming research, other types of illnesses and diseases.

“we’ve taken billions of years to evolve as multicellular organisms, and how these cells interact is really important to health. it’s only multicellular organisms where they (enhancers) seem to play this very important role in conferring tissue specificity on gene expression,” prof. mackenzie said. “that’s not only the secret of appropriate embryonic development, but it’s really important in the homeostasis that keeps us healthy once we’re adults and it goes wrong in diseases.”

the study, “ an ancient polymorphic regulatory region within the bdnf gene associated with obesity modulates anxiety-like behaviour in mice and humans, ” published in molecular psychiatry, found that when one specific gene, the bdnf, is changed via enhancers, it affects the levels of anxiety in the subjects, driven by the enhancer be5.1.

the discovery occurred because enhancers are not limited in what genes they can affect. they hold many jobs and regulate many processes. in this specific case, the same enhancer that regulates appetite in the hypothalamus area of the brain is also tasked with the modulation of mood in the amygdala.

“they (enhancers) are not well understood. but what we do know about them is that they’re bits of dna within the human genome, which turned essential genes off in specific cells at specific times and in response to specific cues,” he said. “many of the genes that we look at are called neuropeptides, and neuropeptides are involved in things like regulating appetite.”

“they’re expressed in part of the brain called the hypothalamus, which regulates appetite, and the same neuropeptides are also expressed in parts of the brain called the amygdala, which modulates mood. so, in many cases, the same neuropeptide is used in a different part of the brain to control a different behaviour.”

understanding the bdnf gene and enhancers

the bdnf gene is a neuropeptide, a protein that binds to other cells via a receptor known as trkb. when that process happens, it sets off a chain of events in other cells that helps foster cell survival. it plays a role in many processes, and that is why it was being studied for its role in obesity and addiction, but it was also found to be associated with anxiety.

“the majority of the cells which are born eventually die because the brain makes too many of them and then trims them and sculpts them into a functional brain and bdnf is involved in this. bdnf is involved in deciding which ones of these cells survive and which ones should die,” said professor mackenzie.

since cells, their information, and cell expression are crucial to overall health, how the bdnf gene interacts and drives changes is an area of study that holds great promise in furthering the progress of medical interventions.

“it’s often referred to as a hub gene, bdnf, because lots of other cellular processes interact with bdnf. it controls so many other aspects of development and brain homeostasis. we can’t really put our finger on its individual role. it seems to have lots of roles,” said mackenzie.

“from what i’ve seen is that it’s got one of the most complicated gene regulation pathways i’ve seen in any protein, meaning that it’s a signal protein, and it’s being used again and again and again in different pathways by being internally regulated in different parts of the brain, and it shows its importance in overall brain function.”

the brain is vital to bodily processes, especially when it comes to mood disorders such as anxiety, so it would appear that before the results of the research were released, the role of bdnf had been severely undervalued.

professor mackenzie states, “cell interactions and gene expression may be the secret of understanding human health and how it goes wrong in disease.” the latest on bdnf is simply more proof that understanding human health can only be achieved through cellular-level exploration and knowledge.

gene expression and cell interactions, which drive genes to perform certain functions, can only occur after rna molecules or non-coding rna molecules undergo a process known as transcription. in this process, rna molecules help convert information stored in genes into proteins that the body uses in various ways.

“we’ve only got 20,000 genes, and what you’ll find again and again in the genome is that the same genes are being used again and again and again in different processes. what decides whether these genes should be used in these cells and these processes aren’t the genes themselves. it’s the enhancers telling them to be turned on at these specific times in these specific tissues,” professor mackenzie said.

anxiety and bdnf expression and enhancers

enhancers work on the same team as rna to promote the proper function of the human body on a cellular level by encouraging or discouraging the transcription of specific genes. they act as a sort of light switch to either turn on or shut off specific changes that can drive changes that affect overall health. in terms of anxiety, the enhancer be5.1 plays a significant role.

the study, when looking to curb appetite in the subjects, deleted the be5.1 enhancer to examine its effects on appetite. while changes in food intake were marginal after the deletion, the mice in the study, particularly females, were shown to have increased anxiety-like behaviour, such as burying marbles.

the mice were then given the anti-anxiety medication, diazepam, and examined again during a burying marbles exercise. after receiving the medication, the female mice that had increased anxiety due to the deletion of be5.1 saw their anxiety-like behaviour reversed.

after noting the results, the researchers turned to human cohort studies to see if they spread across species. they found that the findings were consistent with what they had found during the mouse tests.

the reason why females experienced marked levels of increased anxiety has not yet been determined, but more research is underway to draw a viable conclusion.

“it (gene regulation) seems to be the target of sexual differentiation. except for maybe the y chromosome, we have the same genes, males and females,” professor mackenzie said. “the reason we’re different is because our genes are alternatively regulated in the different sexes, and very much to a high degree. we’re specifically looking for parts of the gene regulatory mechanisms that control response to hormones, and we’ve not found one yet, so we can’t really put our finger on it.”

when looking at current prevalence rates, anxiety is twice as likely to develop in females over males, giving the research a step forward in determining why that may be and what they can do to potentially curb those numbers in people who cope with the mood disorder on a daily basis.

environmental triggers and your dna

fetal and early childhood development are crucial to ensuring happy and healthy futures into adulthood. current research surrounding enhancers and anxiety finds that environmental triggers drive ill health not only on a body-mind level but also on a cellular level. professor mackenzie says it has to do with epigenetics and a mechanism known as dna methylation.

“this is just a change in the dna molecule that involves the addition of what they call a methyl group to specific base pairs within the genome, and that alters the way the proteins interact with the dna. if you’re talking about an enhancer, which requires proteins to interact with it in a very specific way for the enhancer to be active, if you change the chemical presentation of the enhancer to the proteins that bind it and really confer activity on the enhancer then you change the activity of the enhancer,” said professor mackenzie.

he continues, “if you methylate an enhancer, you reduce its activity, and we also know that if you take a mouse and you feed it a high-fat diet or you feed it ethanol, and then you look at the methylation of its enhancers, they’ve changed, the methylation has changed. so, we have a mechanism linking environment with the function of enhancers and behavioural consequences downstream, and this could account for, for example, why children who’ve suffered deprivation or whose mothers or parents have gone through a traumatic event while they were in the womb, why these children often suffer mental health issues, cardiovascular issues, and subsequent disease susceptibility.”

professor mackenzie also touches on evolutionary aspects of anxiety and other chronic disease development, suggesting that “we’ve domesticated ourselves, and not to our benefit.”

“we’re essentially cave people. we’re not that much different from denisovans or neanderthals in terms of our biology. up until the last 80 to 100 years, we were exposed to evolution’s full wrath for most of our evolutionary history, so most of these pathways in the brain are designed to allow us to survive the african savanah a million years ago,” he said. “anxiety response and hyper vigilance were evolved to make sure that you didn’t get eaten. and appetite and addiction or cravings, the reward pathway, would motivate you to find the calories you required to survive.”

“we’ve domesticated ourselves to the degree that were outside of our normal biological environment. we’ve got free access to as many calories as we could ever wish. we’ve got free access, in most countries, free access to alcohol. and we’ve also got 24-hour news and social media. that’s not normal. we’re not living in the environment we evolved to live in. so, it’s not going to be a great surprise that some people are going to suffer problems around that.”

the environment of today is not conducive to evolutionary survival, and because of that, specific events or traumas that occur can essentially switch on anxiety genes and genes that drive other illnesses simply because the modern way of life is not something humans are equipped to handle.

professor mackenzie even goes so far as to say that most people should have some sort of chronic disease in today’s environment, and the people who don’t should be examined for answers.

“i think the most interesting component of our society aren’t the people who get obese because we live in an environment that’s hyper-calorific. it’s the people who are able to stay thin,” he said, giving one example. he continues, “we need to study the non-anxious people just as much as the anxious people.”

using the data to develop new therapeutic approaches for anxiety

to further understand the mechanisms behind enhancers and how they affect the development of illness and disease, including anxiety, professor mackenzie and his team looked at signal transduction pathways, or a flow of information that lives in all cells.

“when two cells communicate with each other, they trigger cascades of protein modification events within the cytoplasm that terminates in the nucleus, so it’s like a chain of information pathway that runs in all cells,” he said. “these signal transduction pathways are actually very good drug targets and have been used through the years to develop lots of different drugs.”

using these pathways and the changes that develop in enhancers tied to the development of diseases and health conditions, including anxiety, medical researchers and treatment developers can essentially create therapies that are personalized and shut off or manipulate the genetic drivers of disease in a way that reverses symptoms by way of new targeted drug therapies. the findings may also help to identify disease risk effectively in a way that encourages a better understanding and management of certain factors that could lead to better prevention techniques.

“you can actually take an enhancer; you can identify a change within the enhancer that’s been associated with the disease. and then when you look at how that change affects the response of the enhancer to the signal transduction pathway, you can see a very strong change that may be part of a disease process,” professor mackenzie said.

“but it may also allow us to identify people who are at risk of disease because if we’re able to identify a drugable pathway that affects the activity of these enhancers, then we may have a way into developing a personalized therapy based around the response of that specific enhancer.”

while the research is still ongoing, and professor mackenzie and his team will need to conduct many more studies before the evidence presented can be used in clinical practice, he is optimistic that they’re “only scratching the very tip of the iceberg” and that much more information is on the horizon regarding dna, genes, and enhancers and their role in anxiety and other health conditions.

the promising work, at its completion, could change the face of healthcare therapies from one-size-fits-some to personalized treatment explicitly designed for harmful changes to someone’s dna, ushering in a new era of medical technology.

angelica bottaro

angelica bottaro is the lead editor at healthing.ca, and has been content writing for over a decade, specializing in all things health. her goal as a health journalist is to bring awareness and information to people that they can use as an additional tool toward their own optimal health.

can genetic tweaks combat anxiety? new study suggests it’s possible

scientific flukes can change the course of health history, and a new accidental discovery regarding anxiety and your genetics is on the road to doing just that.

what it feels like: 'you lose control, and you lose perspective' with anxiety disorder

diagnosed with anxiety disorder: managing stigma, treatments and support

understanding the bdnf gene and enhancers

anxiety and bdnf expression and enhancers

environmental triggers and your dna

using the data to develop new therapeutic approaches for anxiety

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can genetic tweaks combat anxiety? new study suggests it’s possible

scientific flukes can change the course of health history, and a new accidental discovery regarding anxiety and your genetics is on the road to doing just that.

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