Sciences Participating with Arts & Culture in Education

Wired to Worry? Deciphering Genes, Anxiety and You

This article is a tribute to knowledge as a powerful ally against anxiety disorders. It merges scientific insights on the uncertainty woven into our genetics with the art of understanding oneself. Believe in yourselves and know that this new emotion featured in Inside Out 2 does not have to take over your Joy. If you or someone you know is struggling, please reach out. Here is a suicide hotline that is easy to remember: 9-8-8.

The seemingly set-in-stone tale of our biology is written in the letters A, T, C, and G—shorthand for the nucleotides that make up our DNA. Yet there is more to our story than just our genetic alphabet. Unseen epigenetic factors (behavioral and environmental facts that impact our genes) subtly guide the rhythm of our narrative and author a dimension of uncertainty into our lives, including around a common experience among people of all ages and walks of life: anxiety.

When you are looking up menus of restaurants online and reciting your order ten times ahead of arriving, it is not just the ATCGs you were taught in high school biology that are responsible for your anxiety. There is an entire invisible team of epigenetic mechanisms that show that our biology is not an unalterable script. These mechanisms add layers of complexity

to our usual narrative about the determinism of gene strands, highlighting certain feelings while editing out others, and ultimately shaping our experience of anxiety. Uncertainty is not confined to the external world; it resonates within the very fabric of our genetic makeup.

To understand the contributions of genetics, environment and behavior to our individual narratives, it is crucial to first grasp the concept of epigenetics. Common knowledge dictates that our phenotypic traits, like eye color or finger length, are determined by the human genome (DNA). At the molecular level, DNA consists of long chains of nucleotides—Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). These chains of As, Ts, Cs, and Gs, consistent in size and number across all cells, are enfolded around histones, which act like anchors. However, the distinguishing factor between the cells of eyes and those of hands lies in epigenetic mechanisms, explains Nicole Palacio, Ph.D. student at McGill University in the Integrated Program in Neuroscience.

We can view epigenetic mechanisms as small chemical compounds attaching and detaching from the genome; they do not alter the genetic code, but instead regulate its expression. Palacio explains that genes often express themselves by creating coding for proteins which are crucial for orchestrating and carrying out our cell functions. As our cells contain the genetic instructions for diverse tasks, it is crucial at times to be able to “turn on” and “turn off”  genes with various specialized cell functions—i.e. to be able to control their expression. The variance between cells in the eye and the hand emerges in part from differences in protein formation due to the selective expression and repression of DNA, the phenomenon known as epigenetics.

Furthermore, epigenetic mechanisms transcend cell specialization; they encompass gene-environment interactions as well. Palacio explains that environmental factors, such as one’s diet, can impact genes. One specific epigenetic mechanism known as "DNA methylation" occurs when a molecular "methyl" group attaches itself to the DNA strand, thereby repressing the associated gene. To elaborate, these methyl groups target the C nucleotide (Cytosine) in a Cytosine-Guanine sequence (CpG), inducing DNA strands to coil around the histones, thus inhibiting their expression. In layperson’s terms, DNA methylation is akin to crumpling paper; if you crumple your textbook (not recommended unless you are aiming to create more anxiety among students), reading it simply becomes impossible.

Additionally, other mechanisms, such as acetylation—which relaxes the genes around the histones—and non-coding RNA (ncRNA) also influence these epigenetic modifications. Recognizing the importance of these modifications is crucial as they can be inherited by subsequent generations, potentially correlating with behavioral patterns. Just as genes encode proteins that regulate cell functions, any hindrance in their expression could lead to significant changes in our daily lives. The next time your heart races in the grip of social anxiety as you raise your hand in class, consider blaming it on the subtle uncertainties introduced by the methylation of a few DNA strands, an epigenetic process that may have been passed down to you by anxious ancestors.

On that note: while it might seem obvious that epigenetic mechanisms cause environments to shape individuals, their inheritance remains less evident. Gametes’ formation, like spermatozoids and eggs, is highly regulated through a process of cell division called meiosis, aiming to establish a “clean slate” for offspring DNA by wiping away epigenetic markers.

According to a study conducted by Emily Cartwright for Novus Biologicals, however, some of these markers persist and are transmitted to daughter cells and subsequent generations, contributing to contemporary concepts, such as “intergenerational traumas,” commonly circulating on social media.

As humans, our programmed behaviors are influenced by our surroundings, and our responses to stress—a known trigger for anxiety—vary from person to person. Stress is a natural response, designed to help us navigate immediate challenges, such as exam worries. In contrast, anxiety that extends beyond the immediate, persisting even when prepared for situations like exams, can eventually evolve into an anxiety disorder that disrupts daily life. Beyond innate predispositions, the uncertainty of life molds individuals, teaching them to become more prone to stress through firsthand experiences, and thus fostering anxiety. This, in turn, triggers lasting changes in DNA structure through DNA methylation. These modifications in the epigenome persist through cell division, transmitting to daughter sex cells and subsequent generations. This challenges the view that only genetic mutations are inherited, emphasizing that changes in the epigenome, while not mutations, are crucial modifications controlling whether genes are turned “on'' or “off.”

Decoding behavior from a genetic and epigenetic standpoint remains intricate, given that a plethora of genes collectively contribute to our brain chemistry. Various studies adopt different approaches. For example, Genome-Wide Association Studies (GWAS) delve into small DNA sequences, linking them to expressed phenotypic traits. Using GWAS to study anxiety is like learning the language of genetics through flashcards—you might win the spelling bee, but you will continue to struggle to hold a meaningful conversation in that language. Twin Adoption Studies, on the other hand—studies that involve identical twins that were raised in different environments—are much more popular and suggest that about half of the variance in personality is attributed to genetic effects. 

Anxiety is an emotion closely tied to our environment, and ongoing research suggests that the world around us can influence the way our genes function, impacting mental health and potentially affecting future generations. While heredity contributes to anxiety disorders 30-50% of the time, the environment, encompassing work, school, personal life, and traumatic events, plays a more dominant role (50-70%). An article by Steven et al. underscores the need to manage environmental factors, which can lead to epigenetic mechanisms such as DNA methylation, an inherited epigenetic change. By choosing to control your surroundings, you prepare yourself to be more ready in face of the unpredictable experiences that are yet to come in your life, and may be doing any offspring a favor as well.

Examining the collaboration between genes and neural pathways reveals the complex molecular processes influencing our physiological reactions to stress. Genes play a crucial role in regulating stress, since turning “on” and “off” genes impacts the function of the nervous system. We are specifically interested in the autonomic involuntary nervous system (ANS), which has two main parts related to anxiety: the sympathetic nervous system (SNS), activating our “fight or flight” response, and the parasympathetic nervous system (PNS) responsible for the “rest and digest” mode, according to an article in the National Library of Medicine by Jacob Tindle. Information flows in the nervous system in the form of chemicals known as neurotransmitters, and turning up or down their quantities affect these systems.

In the primitive sense, these systems are essential for survival, but epigenetic mechanisms can impair them, leading to anxiety disorders. These disorders are characterized by excessive fear and behavioral disturbances. DNA methylation can make the SNS more reactive, increasing stress responses. Conversely, turning off genes related to calming signals in the PNS can result in less effective relaxation after a stressful event. These changes may seem “permanent” after repeated experiences with stress and are coined as disorders.

Dealing with anxiety can feel challenging, but changes in the epigenome are not irreversible. Anxiety manifests itself in various ways, including worry, fatigue, tension, difficulty concentrating, insomnia, rapid heartbeat, and restlessness. Experiencing an anxiety disorder that modifies our gene expression does not insinuate that it must stay that way. In this hopeless loop of stress, understanding the bidirectionality of epigenetics is crucial for mitigating anxiety and preventing its potential transmission to future generations. Anxiety can be experienced at any point in one’s life and it is challenging to control since the future is fairly uncertain. As events occur randomly and unpredictably, it is necessary to find the ability to navigate and adapt through this unstable current. Amid the different possibilities for paths to take, you possess at least some of the agency needed to choose the best one for you by managing your feelings and responses to life’s unexpected situations. Nonetheless, being more certain of yourself amidst the unpredictability of life is a skill that takes time to learn. 

Several coping mechanisms are available to help with anxiety. Practicing mindfulness and meditation for short durations upon waking up or right before you sleep is very helpful. Meditation consists of focusing on your breath and observing your thoughts as they flow through your brain. In this activity, you will notice the unpredictability of your thoughts. You never really know what comes next, but you can observe and choose to control your attention by bringing it back on your breath, letting the uncertainty be. This is shown to reduce activity in the SNS, the system that causes increased heart rate and regulation of cortisol—the stress hormone. Meditation activates the PNS, promoting relaxation by slowing the heart rate. Moreover, you can also take one mindful minute during your day to focus on your breath and pay attention to the sounds around you, or practice unconventional mediation, which still works just as well. When opting for sound meditation, you will realize that the noise around you is always out of your control. Not knowing what you will hear next emphasizes the unpredictability of life and how you are responsible only for your interpretation of it. For an active alternative, practicing yoga meditation combines both movement and calmness. Additionally, if some of you have a subscription to Chegg Studies, all subscribers have free access to Calm. This mindfulness app offers guided meditations and relaxing sounds for stress management that can also get you better sleep. 

Another effective technique during challenging times is considering what advice you would offer a friend in a similar situation. Research by Igor Grossmann highlights our ability to provide insightful advice to others, advice we do not necessarily follow ourselves. It is easier to think wisely about someone else’s resolutions to unpredictable situations than it is about our own. Therefore, viewing our worries from an external perspective helps channel the wisdom needed for making good decisions for ourselves. 

Additionally, sharing emotions with others promotes a sense of comfort and validation. Card games like We’re Not Really Strangers facilitate open conversations and understanding among friends. It makes you open up and understand each other more fully, helping one another by just hearing each other out. 

If you are looking for a professional opinion, Dawson offers counseling services for short-term therapy through the Dawson Student Assistance Program (DSAP), which can guide you to long-term commitments if need be. Having access to a professional opinion helps you personally cope with your troubles and allows for individual growth. It helps you better navigate unexpected obstacles in your path and embraces a change in direction, if necessary, by helping you gain control over your own self. 

Engaging in hobbies like writing, journaling, reading, listening to music, and baking are all additional ways that might aid releasing stress. As Natasha Daniels says in her book Anxiety Sucks! A Teen Survival Guide, start this weekend by trying out foods that can help with anxiety such as oatmeal, bread, pasta, bananas, and potatoes—bonus points if you make them yourself!

Consider this an invitation to adopt the notion that life often defies our attempts at control, and when that happens, to work to shape your reactions to unexpected events even if you cannot master the events themselves. Whether it is by practicing mindfulness, engaging in self-reflection, or exploring therapeutic interventions, these small steps can significantly impact your emotional state—and maybe your epigenetic mechanisms that influence the expression of your DNA as well. Amidst the uncertainties, find comfort in those small acts of gratitude, in self-complementing in the mirror, and remembering that you, as a complex organism, hold importance. You are not your anxiety. Embrace your story, authored in part by the interplay of genetic letters and the guidance of epigenetic authors, on which your environment and behaviours can make a positive difference, for you and the generations to come.

Bibliography

 Cartwright, Emily. “Epigenetics of Depression: How Can Psychological Stress Alter Your DNA?” Novus Biologicals, 18 May 2022, www.novusbio.com/antibody-news/epigenetics-of-depression-how-can-psychological-stress-alter-your-dna.

Daniels, Natasha. Anxiety Sucks!: A Teen Survival Guide. 1st ed., CreateSpace Independent Publishing Platform, 2016. 

Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences. 2005;102:10604–10609. [PMC free article] [PubMed] [Google Scholar]

Grossmann, Igor & Kross, Ethan. (2014). Exploring Solomon's Paradox: Self-Distancing Eliminates the Self-Other Asymmetry in Wise Reasoning About Close Relationships in Younger and Older Adults. Psychological science. 25. 10.1177/0956797614535400. 

Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences. 2008;105:17046–17049. [PMC free article] [PubMed] [Google Scholar]

Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. American Journal of Psychiatry. 2001;158:1568–1578. [PubMed] [Google Scholar]

Hompes T, Izzi B, Gellens E, Morreels M, Fieuws S, Pexsters A, et al. Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research. 2013;47:880–891. [PubMed][Google Scholar]

Miller CA, Sweatt JD. Covalent modification of DNA regulates memory formation. Neuron. 2007;53:857–869.[PubMed] [Google Scholar]

Murashov AK, Pak ES, Koury M, Ajmera A, Jeyakumar M, Parker M, et al. Paternal long term exercise programs offspring for low energy expenditure and increased risk for obesity in mice. The FASEB Journal. 2015 Advanced online publication. [PMC free article] [PubMed] [Google Scholar]

Non AL, Binder AM, Kubzansky LD, Michels KB. Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety, or SSRI medication during pregnancy. Epigenetics. 2014;9:964–972. [PMC free article] [PubMed] [Google Scholar]

Palacio, Nicole. Interview. Conducted by Khadija Fatima. November 6^th, 2024.

Reik W, Collick A, Norris ML, Barton SC, Surani MA. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature. 1987;328:248–251. [PubMed] [Google Scholar]

Smoller JW, Block SR, Young MM. Genetics of anxiety disorders: The complex road from DSM to DNA. Depression and Anxiety. 2009;26:965–975. [PubMed] [Google Scholar]

Tindle J, Tadi P. Neuroanatomy, Parasympathetic Nervous System. [Updated 2022 Oct 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553141/

Image credit: Puzzle Vectors by Vecteezy