From Experience to Expression: The Role of Epigenetics in Behaviour

Why do we behave the way we do? More intriguingly, why do people, even siblings raised in the same home, attending the same schools, growing up  in the same environments, develop such different behaviors? When studying behavior we often try to pinpoint its causes. Often behaviours can be attributed to either the environment or genes, nature or nurture if you will. And this makes sense, the environment can help explain lots of things, in fact the number one predictor of overall psychological well-being is socioeconomic status (Manstead, 2018). But on the other hand, we also seem to ponder a lot if people are ‘born’ with a particular trait (for example,  when you wonder where your genius came from) or if we acquired traits throughout our life as a result of our environment. 

In a similar vein, genes can also have a role in determining lots of things: the colour of your eyes, the types of cells in your lungs, your blood type and such. Genes are like the instruction manual for building and running our bodies. For the most part,  genes are expressed at exactly the right place; you'll very rarely have a photoreceptor where a lung cell should be.  But the interesting thing is that all of our cells have a full copy of all of our DNA, so how does a lung cell know not to become a photoreceptor when the body is growing?  Well, there are lots of ways gene expression can be regulated. All cells in our body have the same DNA, but not all genes are active in every cell, given intricate gene regulation. During embryonic development, signaling pathways guide cells to differentiate into various tissues. Eyes and lungs develop differently for example, so genes that code for lung tissue cells won’t be activated in our retina for example. Hence no photoreceptors cells where alveoli cells should be - pretty neat. But these are not the only ways in which genes can be regulated (stay tuned). 

For a while, psychology saw environmental factors and genetic factors as very separate perspectives through which we could try to determine personal disposition. But, through a closer look at gene expression, and exactly how, why and when genes are expressed, a fascinating interplay between our environment and our genes has been uncovered.

Epigenetics is the study of how environmental factors can influence the expression of our genes without changing the underlying DNA sequence. The term "epigenetics" comes from the Greek word "epi," which means "over" or "above." This reflects how epigenetic changes act on top of or alongside our genetic code, regulating when and how genes are turned ‘on’ or ‘off’ (expressed or not expressed). Epigeneticists have reformed the views of nature and nurture by elegantly revealing the intertwining reality of nature influencing nurture, through biology. This has alleviated the grips of a ‘deterministic’ genome but rather a dynamic epigenome, malleable by experience. 

So what does this have to do with behaviour? Where epigenetics and psychology gracefully high-five is firstly in the understanding that biology can and does influence our behavior.  For example, neurotransmitters like serotonin and dopamine are vital for regulating mood and behavior and variations in these neurotransmitters can predict susceptibility to anxiety and depression. Elevated cortisol levels can increase anxiety and even mediate social behavior (Kuhlman et al., 2018), a more reactive amygdala in the brain is associated with stronger emotional responses and impulsivity, and the list goes on (Phelps et al., 2004).  

As we see, behavior can often be described and unpacked by neuroscience through biological processes in our brains and the chemical interactions of neurons. Very, very importantly though, your biological makeup may predispose you to certain behaviors, though it doesn’t guarantee that you will develop a specific trait; rather, it creates a likelihood for that trait to manifest. Nonetheless all of these proteins, hormones, and receptors that can strongly influence behavior - are coded for by genes. This prompts the question of how our environment has shaped not only our genetic makeup but more specifically, the expression of these genes in our phenotype. 

Behavioral epigenetics undertakes the ambitious task of elucidating how genetic expression, modulated by experience, may predispose individuals to certain behaviors. While we have some understanding of how genes can influence behavior, recent research seeks to clarify how environmental factors actively shape the regulation of these genes. And as a consequence, how does the alteration of behavior-related genes as regulated by our environment, give us insight into individual differences in behaviors such as chronic stress, addiction, and aggression? Here, I aim to build a case for the role of epigenetics in offering insight into such individual differences. 

A Tale of Adversity

What does it mean to respond to our environment? On a behavioral level, it could mean altering our actions based on the stimuli we encounter, a process that generally serves us well; run when there’s a lion, hunt when we are hungry, the whole song and dance. But our biology can too be moulded to better suit our environment; in accordance with the conditions we face. 

Now, the problem arises when there’s a mismatch between the environment we’re biologically prepared for (the anticipated environment) and the environment we actually live in. We can even start before birth, following a developing foetus. If a mother faces a world of scarcity, where food is limited and survival is a challenge, her body will be deprived and malnourished, shaping the fetal environment in which her child develops. The fetus, in turn, develops phenotype designed to maximize survival under such harsh conditions. The result? The baby can become an efficient machine that grips onto glucose and has a hypothalamus  attuned to taking in as many nutrients as it can. These adaptations are the reasons your life, in this anticipated environment may be spared. But what happens if Mom then moves to Western California, next to a McDonald’s, in a world where calories are cheap and abundant? The very survival mechanisms that once made sense now predispose a child to a slow metabolism and glucose retention. A similar story became one of the first examples of evidence for epigenetics.  

Starting jovially in post World War Two Denmark, the Dutch Winter Famine of 1944  marked one of the first studied cases of environmental circumstances causing heritable changes to our genes.  Following the end of the War, a German blockade in Western parts of the Netherlands left the population in a catastrophic food shortage. This period was short lived, and in particular affected a previously well-nourished population. The intrigue of this story were the mothers undergoing gestation during this period - or more particularly their children.

Thankfully, the Dutch also happened to be exceptionally reliable medical record holders and wrote all this stuff down, enabling us to understand the generational effects of this famine. Birth records seemed to show that, despite experiencing severe malnourishment around conception, women birthed babies who paradoxically tended to be overweight, were highly vulnerable to obesity, and whose children were also more prone to obesity. Now, why would this happen ?

Biological studies have elegantly revealed the nuts and bolts of this strange phenomena.  A landmark study (Heijmans et al., 2008) managed to recruit 60 individuals who were conceived and born during this harsh winter. Their genome (complete set of genes) was analysed, revealing an  interesting singularity in this post-war generation compared to the general population. It seemed there was much more expression of a gene called insulin-like growth factor (IGF2) , in those exposed to famine in early gestation. High expression of IGF2 often contributes to conditions like obesity, insulin resistance, and metabolic diseases by increasing energy storage and disrupting glucose balance. But over-expression was not seen within the genome of these childrens’ mothers, nor was within their siblings.  So what was going on? Clearly purely genetic inheritance was not enough to explain this difference. 

A closer look at gene expression revealed lower DNA methylation at the IGF2 gene’s differentially methylated region (DMR). DNA methylation is  an epigenetic process where a chemical group is added to the DNA, typically silencing genes by preventing transcription factors from accessing the DNA strand, thus that gene being expressed.  Hence, this permits regulated gene expression without needing to change the DNA sequence itself. Thinking evolutionarily, this is quite efficient. We don’t have to gamble as to which gene we want to keep in our genome or lose through  natural selection, but rather methylation  allows for a gene to be expressed, as well shall see - when it’s needed.  

In our case, reduced IGF2 methylation increased gene expression and disrupted imprinting, allowing both alleles to be expressed. Strikingly, these methylation patterns were also seen in the next generation, demonstrating that environmental influences can leave heritable biological marks. This isn’t just genetic inheritance—it’s epigenetic inheritance, where experience-driven modifications shape gene expression across generations. Once again, this is actually really useful. Early development is when the fetus is especially sensitive to environmental cues, and so if nutrients are scarce, the developing body ‘assumes’ that scarcity will persist after birth, prompting  a biological preparation for a world of deprivation. 

The story of the Dutch Hunger Winter highlights two key insights: first, our experiences can directly shape gene regulation, meaning we may not express the same genes our parents do; second, these regulatory changes can be passed on, showing that environmental influences on biology can begin long before birth.

As the notion grows that  some of our predispositions to certain behaviors may be biological, it becomes more intriguing to understand how our environment has had a role in shaping us into who we are. Examining these questions through the lens of epigenetics may provide insights into why some individuals exhibit certain behaviors while others do not. Epigenetics can shed light on how life experiences leave lasting molecular imprints, and we hope to unravel in this regard the profound mystery of how our experiences translate into enduring changes in our biology and potentially, our behavior.  Here, we will endeavour to discuss predispositions to stress, aggression and addiction, as you can see, in consistency with our jovial tone.

Stress 

It’s a common notion that early experience may shape how we respond to stressful circumstances, and this may well be the case. But firstly, how does our stress response work? 

The stress response is designed for intermittent use, to help us run from the usual saber-tooth tiger or summon the strength to fight off an opponent, and this is really useful. But the thing is, we seem to be frequenting a lot less wild cats these days and physically running and/or fighting is lower on our lists of top essential skills - instead we experience more prolonged stress. Unfortunately for us, when stress response is constantly activated, it results in persistently elevated cortisol levels with widespread negative effects. Imagine your heart pounding and muscles tensing not just in moments of real threat but through your entire 9-to-5. Over time, this chronic activation can leave you with stuff like stomach ulcers and increased vulnerability to disease - not so useful. The real issue is that chronic stress, particularly in environments of consistent adversity such as childhood maltreatment, places an epigenetic burden on our cells. This may explain why some individuals develop a heightened sensitivity to stress, carrying a biological weight long after the threat is gone.

One of the most impactful studies in this field examined the effects of maternal care on infant development. In the rodent world, one of the most crucial maternal behaviors is licking and grooming (LG)—a caregiving behavior observed in rat mothers toward their pups. In Liu et al.’s (1997) study, the absence of this maternal care led to rats that were more fearful, displayed heightened stress responses to novelty, and engaged in fewer exploratory behaviors. These neglected rats coped with stress far less efficiently than their well-nurtured counterparts. More importantly, this stress vulnerability persisted throughout their lives, hinting at a deeper more complex biological mechanism, one that epigenetics could explain.

Remarkably this experiment fluently uncovered parts of the epigenetic mechanisms that predispose these behaviors. The neglected rat group exhibited methylation of the Nr3c1 exon 1, a promoter for NGF1-A, a gene critical for driving the expression of glucocorticoid receptors (GRs) in the brain. GRs play a pivotal role in inhibiting the stress response by suppressing the release of CRH (corticotropin-releasing hormone) and ACTH (adrenocorticotropic hormone) through a negative feedback loop. However, the addition of methyl groups suppressed the expression of NGF1-A, effectively “closing” the DNA to transcription and making this DNA strand less accessible. As a result, these rats developed fewer glucocorticoid receptors, impairing their ability to regulate their stress response. To highlight the potential of epigenetic inheritance for the stress response regulation, even the next generation of non-neglected pups exhibited behavioral and genetic patterns similar to their neglected parents. 

We now see the potential for the postnatal environment in directly shaping the genome of a developing rat, but the case is thought to be the same in humans too. Research on adults who experienced severe childhood trauma has revealed strikingly similar correlations between glucocorticoid receptor methylation and heightened stress reactivity (McGowan et al., 2009). These findings underscore the intricate interplay between early life experiences and gene expression related to stress, creating an epigenetic signature that may persist across generations.

Aggression 

What makes some more aggressive than others? Is it a trait implemented into our biology, sculpted by experience, or something in between? Let’s begin by examining some biological factors that may predispose this behavior.

Oxytocin, the "social neuropeptide," modulates social behaviour, promoting connection in response to care while decreasing social bonds in response to neglect (Heim et al., 2009). It has a dual role—enhancing social relations but also heightening aggression under provocation, particularly in those with oxytocin receptor (OXTR) abnormalities (DeWall et al., 2014; Ne'eman et al., 2016; Finkel, 2014). Individuals prone to aggression often show impaired oxytocin function, influenced by epigenetic modifications like DNA methylation. Increased OXTR methylation, often linked to early trauma, reduces receptor transcription and weakens oxytocin’s regulatory effects on behavior (Veenema, 2012; Unternaehrer et al., 2015; Ziegler et al., 2016; Smearman et al., 2016; Gowin et al., 2017). Even prenatal environments matter—newborns of mothers with substance abuse or psychopathy during pregnancy exhibit hypermethylated OXTR, increasing the likelihood of callous-unemotional traits and persistent aggression (Cecil et al., 2014; Frick & White, 2008).

Serotonin is also deemed to be key in mediating aggressive behaviours. The hormone seems to inhibit aggression by activating receptors in the prefrontal cortex, which acts as a "brake" on the amygdala, a brain region central to our fear response. This regulation typically curbs impulsive responses to threats. Low serotonin levels though, are often seen to weaken impulse control, increasing the likelihood of reactive aggression.

Studies have established connections between epigenetic changes in the serotonergic system and adverse experiences. Two key regulators of serotonin are the SLC6A4 gene, which is responsible for serotonin reuptake, and monoamine oxidase A (MAOA), which breaks down serotonin (Shih et al., 1999). One notable study examined monozygotic twins (an ideal genetic model given these pairs share all genetic similarities from birth) investigating the effects of bullying. The findings revealed that bullied children exhibited higher SERT methylation levels compared to their non-bullied twin. Specifically, there was an increase in SLC6A4 promoter methylation (resulting in decreased SLC6A4 transcription) between ages 5 and 10 (Ouellet-Morin et al., 2013). Practically, this change may result in a greater likelihood of dysregulated serotonin levels in the brain, potentially predisposing individuals to aggressive behavior. These findings have been supported in other studies that highlight the impact of various social stressors. For instance, adolescents from low-income backgrounds show increased SLC6A4 methylation and heightened amygdala activation in response to fearful stimuli (Swartz et al., 2017; Beyer et al., 2015; Antonucci et al., 2006). 

Studies in rodents have permitted a deeper dive into the mechanisms underpinning genetic regulation of serotonin in response to adverse environments. In rats, peripubertal stress shows amygdala connectivity paired with increased MAOA expression in the frontal cortex. This can lead to a tendency to break down serotonin when it is actually useful and induce epigenetic changes via H3 acetylation of MAOA (Márquez et al., 2013). Acetylation offers another clever way of genetic regulation apart from altering the DNA sequence. Typically, DNA wraps around histone proteins to form chromatin, the cellular storage structure for DNA. Acetylation is the addition of an acetyl group (−COCH₃) to these histones, which alters the configuration of the wrapped DNA and results in a more relaxed structure. This increased accessibility allows transcription factors to more easily read the genetic code, facilitating the expression of specific genes.

Since scientists do quite well detailing abstract behaviours with little molecules, one might wonder: how exactly does environmental stimuli translate into biochemical changes in our bodies that subsequently silence genes? The short answer is that we don't fully understand the mechanisms yet, although various candidate pathways exist that propose how environmental stimuli can be converted into biochemical cascades, much of the research remains correlational. We observe that certain experiences coincide with gene alterations and find mechanisms for those alterations, yet we cannot always map the complete molecular sequence that drives these changes from external straight to internal. Understanding these causal pathways through a biological lens remains a compelling focus within the field of preventative epigenetics.

Addiction 

Addiction presents a particularly intriguing case of behavior—one that seldom offers any health benefit and is often deeply harmful, yet individuals repeatedly engage in it. Epigenetics may help explain why certain negative behaviors persist despite their consequences. In the case of addiction, genetic modifications can reinforce compulsive behavioral cycles, making it increasingly difficult to escape the pattern of repeated drug-seeking.

Addiction involves repeated substance use despite negative consequences and is often linked to pathological memory formation. Long term potentiation (LTP) strengthens synaptic connections between neurons through repeated activation and plays a key role in learning and memory. In reward-related learning, LTP reinforces associations between behaviors and positive outcomes, increasing likelihood of repeating certain behaviours. This process is enhanced by D1 dopamine receptor (D1DR) activation, elevated in drug users  (Gurden et al., 2000). Normally, dopamine reinforces reward-related learning—when something feels good our brain rewires slightly to make us more prone to seek it again.  But in addiction, unnaturally high dopamine levels hijack this system, reinforcing compulsive drug use, despite the negative consequences on general health we experience post drug intake (hopefully this doesn't sound too familiar). 

LTP, fundamental to associative learning, is often seen as a key mechanism in addiction. Strengthened synapses under high dopamine levels may cause drug-related cues to be disproportionately valued, leading to loss of control over behavior - a hallmark of addiction.  At the genetic level, synaptic modifications can trigger lasting changes in gene expression, especially with repeated drug exposure. This is why addiction is often described as "pathological learning"—normal memory mechanisms like LTP are usurped and overused in drug-related learning, making drug-seeking behaviors deeply ingrained and resistant to change.

So, where does epigenetics come in? Genome-wide studies have identified numerous CREB target genes linked to neuronal excitability and synaptic function, many of which are regulated through epigenetic processes like acetylation and methylation (Renthal et al., 2009).

While direct links between epigenetics and synaptic plasticity are still being explored, CREB plays a key regulatory role. CREB, activated by various drugs in both D1- and D2-type medium spiny neurons (MSNs) of the nucleus accumbens (NAc), increases neuronal excitability (Dong et al., 2006). This heightened excitability makes it easier for neurons to strengthen connections in response to drug-related cues, reinforcing pathological memory formation. CREB also promotes synaptic plasticity by enhancing GluN2B NMDA receptor subunit expression and reshaping neuronal morphology (Bellone & Lüscher, 2012; Dong & Nestler, 2014). These changes contribute to the plasticity of neurons and the reinforcement of drug-related associations. This illustrates how drugs induce epigenetic modifications that may reshape synapses, in turn reinforcing vulnerability to respond behaviorally to drug related cues, consuming this ‘reward’ and making addiction all the more persistent.

Tolerance is also a major problem in addiction, where consumption needs to incrementally increase to replicate drug-related effects. CREB activation through drug-intake increases transcription of the prodynorphin gene histone modifications, leading to dynorphin peptide expression. Dynorphin signaling suppresses the brain’s reward system by acting on κ-opioid receptors in the ventral tegmental area (VTA), an area central to reward-related learning. This reduces dopamine release in response to rewards, diminishing drug-induced euphoria and requiring higher doses to achieve the same effect.

Although one again, we lack clear mechanistic pathways to detail the epigenetic changes in the brain during addiction, these findings may suggest addiction is more than just a matter of choice. Drugs may abuse natural biological systems, altering gene regulation through epigenetic modifications and worsen one’s odds of remaining in a damaging cycle of addiction .

Concluding Thoughts 

As we can see, epigenetics has done a remarkable job of revealing how our experiences  mark us on a biological level. The once-clear line between nature and nurture has become a blurred construct. By understanding that behavior can be chemical, we recognise that our response to these chemicals is influenced by our unique biological makeup — potentially shaped both by the biology we inherited and our life experiences. This perspective shifts us a little away from the notion of a genetically predetermined phenotype. Instead epigenetics emphasises how the environment can shape us, and begins to describe mechanistic explanations for this phenomenon.

Of course, it’s important to note some key points when discussing genes and behavior. Firstly, there’s never a straightforward “gene for” a trait - behavioral traits are highly polygenic, and as mentioned earlier, they merely predispose us. Just because somewhere along the road something got methylated, this does not mean you’re destined to be impulsive, stressed and aggressive. Instead, recent research demonstrated your epigenome, specifically your neuronal epigenome regarding behavior is dynamic not only in early experiences but  throughout your lifespan. 

In any case, epigenetics seems to make a pretty compelling case for how our environment literally gets under our skin.

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