Trauma Related Genetic Changes Increase Risk of Drug Addiction

Recent studies have examined how early exposure to stress or drug can cause lasting changes in behavior, genes, and other body functions.
childhood- abuse- effects can be genetically passed down and lead to increased risk of addiction

Table of Contents

Understanding the Link Between Early Life Experiences and Addiction Risk

In 2019, a U.S. survey found that about 20.8% of people aged 12 or older used illegal drugs in the past year, but only 3.0% had a drug use disorder.

This shows that drug addiction affects only some people, and researchers are still trying to determine why.

Many studies suggest that tough experiences during childhood can make a person more likely to develop mental health issues like addiction, depression, or PTSD later in life.

The teenage years are also important for understanding how addiction can develop in adulthood.

Changes in our genes (epigenetic changes) can happen because of things we experience in our lives, and these changes might affect how likely someone is to become addicted to drugs.

Some recent research has looked into how certain gene changes can affect addiction risk (Kaplan et al., 2022), but there’s still more to learn about other gene changes.

New ways of studying the brain and genes have helped researchers better understand how our environment, genes, and brain function can affect addiction.

The following research from the past five years shows how difficult experiences during childhood can lead to a higher risk of addiction later in life, emphasizing how these experiences can change how genes work in animals.

Difficult experiences during early life can significantly impact a person’s mental health and may increase the risk of addiction as they grow older.

Exposure to stress or drugs during this critical time can lead to lasting changes in behavior, gene activity, and other biological factors.

However, researchers don’t fully understand how these changes make a person more likely to develop addictive behaviors later in life. 

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Gender Differences in Addiction Borne of Traumatic Experiences

Gender plays a role in how addiction develops and early life difficulties affect people.

According to studies, women tend to have more adverse experiences during childhood and are more affected by these experiences, often facing serious stress-related problems as adults compared to men.

Studies show that men, on the other hand, are more likely to start using illegal drugs and to use IV drugs than women.

In animal studies, male rodents start using substances earlier than females. Still, female rodents are more affected by early life stress and show more stress-related behaviors than adults.

The gender-specific aspects of addiction are probably related to changes in our genes (called epigenetic changes) that affect behavior and how we respond to rewards.

Both men and women have different levels of sex hormones, and these hormones can change how genes work and are organized. Since past research often didn’t include female subjects, we still don’t know much about the differences between men and women regarding the molecular aspects of addiction.

What we Can Learn from Rat Studies About Trauma and Addiction

rat studies on addiction genetics and epigenetics
Studies utilizing rats have answered many questions about addiction and genetics.

Early life stress, like childhood maltreatment, parents splitting up, or living in poverty, can cause changes in behavior, genes, and other biological factors.

In people, these types of stress can lead to changes in brain structure and activity, which might cause mental problems. Stressful childhood experiences can also make it harder for people to process rewards and learn from them.

Scientists study early life stress in rodents by separating baby rodents from their mothers. These studies help us understand how early life stress can affect how the brain responds to rewards and motivation.

The experiments can vary in the age of the rodents, the length of time they are separated from their mothers, and how researchers handle them. Some experiments use mild stress, while others use severe stress.

Baby rodents exposed to stress by being separated from their mothers show different behaviors when they grow up, depending on their gender.

Female rats exposed to stress as babies act differently as adults, taking more risks and showing increased movement when given drugs like cocaine.

These changes in behavior could be connected to stress-related changes in genes that are important for reward and stress processing in the brain.

On the other hand, male rats exposed to stress by having limited nesting materials show different responses to drugs like morphine as adults.

These differences might also be related to changes in gene expression in the brain. In some cases, stress during early life can lead to increased drug use and changes in brain activity in adult male mice.

Overall, early life stress can have long-lasting effects on both male and female rodents, but these effects may differ for each gender.

Social Isolation: Impact on Addiction Susceptibility in Adulthood

genetics social isolation during adolescence and addiction

Early life stress can also affect individuals during their teenage years. Studies using mice show that long periods of social isolation during adolescence can lead to increased drug use and changes in adults’ brain response to drugs.

These changes seem different for males and females and may be related to how specific genes work in the brain.

The amygdala, a part of the brain, plays a central role in how early life stress affects behavior related to rewards.

There are differences in gene activity between males and females, and certain genes may be important for understanding how addiction-like behaviors develop in both sexes.

Some molecules, like oxytocin, could be potential targets for drug treatment since early life adversity can affect how they work and lead to problems with social behavior and emotions.

More research is needed to understand the sex-specific epigenetic changes after teenage social isolation and how they affect the risk of addiction in adulthood and identify potential treatment options.

Stress Vulnerability in Females

Studying male and female subjects in preclinical research is crucial for understanding the effects of early life adversity on adult addiction and stress vulnerability. There aren’t many studies that focus on early-life adversity and addiction-like behavior in females, but some examine adult stress vulnerability in females. For example, when baby mice are separated from their mothers and later experience social isolation during adolescence, they tend to be more resilient to anxiety and depression-like behaviors as adults. However, maternal separation alone increases their vulnerability to these behaviors. In females, some effects of maternal separation, like an increased inability to experience pleasure, are similar to those usually linked to low estrogen levels. Maternal separation also affects adult female mice by increasing the expression of a specific receptor related to stress response and altering DNA patterns in certain regions. The effects of early life adversity are also influenced by the individual’s genetic vulnerability to stress disorders or addiction. Some rodent models have been used to study stress vulnerability, but there is still limited data on early life adversity in these models. Adolescent mice from a specific strain display less social behavior and increased anxiety than other strains. Another study found that both vulnerable and non-vulnerable rat strains respond more strongly to drug rewards after experiencing early life stress. This suggests that early life adversity might be a more significant risk factor for adolescent addiction than genetic vulnerability alone.

Early Life Exposure to Drugs

exposure to drugs in adolescence

Childhood and adolescence are important periods where early life adversity, such as stress, can strongly impact an individual’s likelihood to start using drugs and facing a higher risk of overdose. 

Exposure to drugs early in life can also make a person more susceptible to drug addiction.

Studies on animals have found that the effects of early-life drug exposure depend on the specific drug, sex, and experimental conditions used.

For example, exposing rodents to cocaine during their early life influences addiction-related behaviors, such as habit formation and difficulty adjusting to new information.

Interestingly, the effects of cocaine exposure during adolescence seem to differ between male and female rodents. 

Males who increase their cocaine intake during adolescence exhibit more habit-like behavior as adults. In contrast, females with a history of stable cocaine intake during adolescence are more prone to habit formation if they encounter cocaine again in adulthood. 

These effects appear to be linked to the animals’ motivation and learning processes rather than just the exposure to the drug.

Studies have also shown that the effects of adolescent drug exposure on adult behavior can be drug-specific. For example, adolescent exposure to THC, the main psychoactive compound in cannabis, affects adult behavior differently than exposure to cocaine.

It is also important to note that early life exposure to one drug can sometimes lead to addiction to another drug. 

For instance, teenagers who use prescription opioids for non-medical purposes are more likely to develop substance use disorders involving alcohol, cannabis, and heroin.

In animal models, exposure to one drug during adolescence can lead to increased sensitivity to the effects of another drug later in life, with different outcomes for males and females.

In summary, the effects of early life drug exposure on adult behavior, gene expression, and epigenetic factors are complex and depend on various factors, including the specific drug involved, the sex of the individual, and the experimental conditions used in the study.

Exposure to Drugs in Early life Affects Adult Gene Expression

The long-lasting effects of drug exposure during childhood and adolescence may be due to changes in gene activity and the epigenome (factors that control gene expression without altering the DNA sequence).

Studies on animals have found that exposure to THC (the main psychoactive compound in cannabis) during adolescence leads to different gene activities in male and female brains.

These changes can affect the animals’ hormone activity and learning processes, possibly influencing their motivation for drug intake later in life.

Adolescent drug exposure can also lead to changes in brain functions, such as altered dopamine signaling. For example, exposure to opioids during adolescence can increase the risk of opioid addiction in adulthood.

Studies on animals suggest that early opioid exposure may affect the development of brain reward systems. In male mice exposed to oxycodone during adolescence, genes related to dopamine signaling are less active, and the epigenetic markers responsible for repressing gene expression are more abundant in their adult brains compared to animals not exposed to opioids.

Alcohol exposure during adolescence can also lead to addiction through epigenetic mechanisms. Studies on animals show that adolescent alcohol exposure can cause changes in gene activity and histone modifications (epigenetic markers that affect gene expression) in specific brain regions.

By modifying these epigenetic markers, researchers have been able to reverse the behavioral effects of early alcohol exposure in animals, suggesting that such approaches may have potential therapeutic applications.

Early drug and alcohol exposure can lead to long-lasting effects on gene activity and epigenetic factors, contributing to addiction later in life. Research on animals has highlighted the sex-specific nature of these changes. It has provided insights into potential interventions that may help prevent or treat the consequences of early life stress and drug exposure.

Exploring Enhancers, Proteins, Inheritance, and Gender Differences

Epigenetic changes, which affect gene activity without changing the DNA sequence, can happen all over the genome.

While most studies focus on gene promoters (regions that control gene activity), changes at non-coding genomic elements, like enhancers, are also crucial for understanding the long-lasting effects of early life adversity on both males and females.

For example, a specific genetic variation in an enhancer of the cannabinoid-1 receptor (CB1R) gene is linked to human addiction. Deleting this CB1R enhancer in mice reduces alcohol intake and certain behaviors related to cannabinoids (compounds found in cannabis), and also causes changes in anxiety-like behavior in both sexes.

Other well-known enhancers are linked to stress regulation and addiction, including those for KF506 binding protein 5 (FKBP5). Genetic variations in FKBP5 are associated with an increased risk of stress-related psychiatric disorders in people who experienced childhood trauma.

Additionally, recent research has found genetic variations related to cocaine dependence and the impact of childhood environmental exposures on cocaine use disorders.

Differences between males and females in their response to early life adversity could also be due to their different protein profiles at baseline.

For example, differences in circulating hormones and signaling factors may affect how each sex responds to stress and drugs.

Studies have found that brain signaling and reward pathways proteins are expressed differently in male and female brains. These differences may lead to varied behavioral outcomes after drug exposure.

Epigenetic changes caused by early life stress can also fundamentally alter how individuals respond to drugs like cocaine later in life.

Research in specific brain regions has shown that early life stress and drug exposure can cause changes in the way certain brain cells function, which can contribute to altered drug effects.

Recently discovered modifications, such as dopaminylation, have also been shown to play a role in cocaine reward behavior and may increase vulnerability to cocaine addiction following prior drug exposure.

This highlights the connection between early life adversity, epigenetics, and changes in drug effects.

Negative Childhood Effects Can Last More Than a Lifetime

childhood- abuse- effects can be genetically passed down and lead to increased risk of addiction

The effects of difficult experiences during early life can last a very long time, even beyond a person’s lifetime, affecting future generations.

Research on animals has shown that when parents are exposed to drugs during their adolescence, it can have various effects on their children and even grandchildren.

For example, when mother and father rats are exposed to THC (a compound found in marijuana) during their adolescence, it can cause changes in their children’s genes and brain function, with some differences seen only in female offspring.

Studies also found that when mother rats were exposed to morphine during adolescence, their adult offspring tended to consume more cocaine, while father rats exposed to morphine during adolescence had offspring that consumed less cocaine.

Interestingly, these studies suggest that the parent’s sex might influence how their drug exposure affects their children.

Experiences of early life stress in mother rats can also affect the brain development of male and female offspring.

All these findings highlight how parental drug exposure during adolescence can lead to a higher risk of addiction in their children and that this risk can vary depending on the child’s sex.

Early life adversity has different effects based on sex, brain region, and type of experience. These experiences can influence the risk of addiction in adults, with the underlying mechanisms involving changes in gene expression and brain function.

Most studies have focused on male subjects, but it’s important to include females in future research to understand the factors contributing to addiction susceptibility fully.

Sources

[1] Key Substance Use and Mental Health Indicators in the United States: Results from the 2019 National Survey on Drug Use and Health

[2] Genomics and epigenomics of addiction

[3] Adverse childhood experiences and associated health outcomes: A systematic review and meta-analysis

[4] Adverse childhood experience effects on opioid use initiation, injection drug use, and overdose among persons with opioid use disorder

[5] Early life adversity: Epigenetic regulation underlying drug addiction susceptibility

[6] Adolescent social isolation increases cocaine seeking in male and female mice

[7] Sex and Estrous Cycle Effects on Anxiety- and Depression-Related Phenotypes in a Two-Hit Developmental Stress Model

[8] Are trait impulsivity and exposure to cannabis or alcohol associated with the age of trajectory of cocaine use? A gender-specific dimensional analysis in humans with cocaine dependence diagnosis. 

[9] Adolescent Alcohol Exposure Epigenetically Suppresses Amygdala Arc Enhancer RNA Expression to Confer Adult Anxiety Susceptibility

[10] Chapter Six – Exposure to drugs of abuse induce effects that persist across generations

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