Photo by Marlon Lara
I learn something new about addiction and recovery almost every day.
I learn from every patient I see. Sometimes I learn from my peers, and sometimes I learn from scientists working in their labs.
One of my colleagues told me about results reported in this article — “On the Early Life Origins of Vulnerability to Opioid Addiction” — published in November 2019 in The Journal of Molecular Psychiatry.
I glanced at the abstract, which included the phrase “early life adversity.” That piqued my interest further. I’m well aware of the effect of childhood trauma on vulnerability to addiction, but that phrase got my attention.
Early life adversity.
That’s a new one for me, in this context.
I’m familiar with “adverse childhood experiences,” which are also known as ACEs. Clear and unmistakable evidence links ACEs to a host of physical, emotional, and behavioral disorders later in life, including alcohol and substance use disorders.
However, when I cracked open this article — meaning I downloaded the .pdf, put my laptop display on night mode, and got comfortable — I learned that the phrase “early life adversity” means something else entirely.
Whereas ACEs typically refer to trauma an individual experiences during childhood or adolescence, early life adversity — called ELA — refers to trauma experienced in the first few months of life.
And the fact that the article was published in a hard science journal — believe me, molecular anything is hard — meant to me that the authors may have found a chemical mechanism in the brain, influenced by early adversity, that’s related to addiction.
That’s new and interesting.
The Influence of Early Experience on Addiction
We actually know quite a bit about the effect of early life experiences on the subsequent development of alcohol and substance use disorders. A landmark paper published in 1998 called the ACE Study coined the phrase adverse childhood experience (ACE) and offered evidence connecting ACEs to increased risk of developing post-traumatic stress disorder, depression, anxiety, and alcohol/substance use disorder. The paper also led to an entirely new approach to treatment called Trauma-Informed Care.
Evidence tells us that early trauma increases the risk of later trouble: that’s the short version.
Trauma during childhood and adolescence can cause dysregulation and maladaptive responses in two areas of the brain that have a significant impact on behavior — the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. The SNS initiates our fight or flight response, while our HPA axis regulates our responses and adaptations to stressors present in our environment. Studies show that early trauma can lead to toxic stress, which, through a series of chemical changes in the SNS and HPA, increases the likelihood an individual will develop physical, emotional, and behavioral disorders later in life.
That much we know.
Examples of ACEs that may cause toxic stress include exposure to physical, emotional, or sexual abuse, physical or emotional neglect, domestic violence, divorce, witnessing violence, and more. We know this because scientists asked people detailed questions about their early life experiences, cross-referenced their answers to their physical and mental health as adults, and realized that the more ACEs a person reported, the more likely they were to develop the pathologies mentioned above.
Here’s the rub: the ACE study relied on self-reporting, which means memory, which means the experiences people reported must have occurred during periods of life from which they had memories. This new paper though talks about the effect of experiences that occurred during infancy. Although we were all infants once, no one remembers infancy: our brains don’t start storing experiences as permanent memory until around age seven.
So how do the authors of the paper know traumatic experiences in the first few months of life can change the brain?
Behavioral Experimentation in the Rodent Model
As a person who has been adopted by about a dozen shelter dogs and neighborhood cats, I have always emotionally struggled with animal labs. When I started attending addiction medicine conferences in the 90s, I would take bathroom breaks or go for coffee when neurobiologists would start to talk about their rodent data, but after I sat through a few lectures, I came to understand how we can extrapolate data from the brains and behavior of lab animals to the brains and behavior of humans living free in the real world.
So, by way of explanation, here’s a quick lesson in neurobiology: the neurons (brain cells) in a rodent function exactly the same way human neurons function in the primitive part of the brain where drugs and alcohol cause their damage. We know this through direct observation: we’ve looked, tested, and verified the electrochemical nature of animal and human neurons countless times since the 1950s. From crayfish to primates, all neurons rely on an identical mix of potassium, calcium, and sodium to create what’s called an action potential. Action potentials cause neurons to fire. Neurons firing cause every thought we’ve ever had and every thought we will ever have. Neurons firing also cause all our behavior, meaning everything we’ve ever done and everything we will ever do.
That’s how we work.
I bet you didn’t expect a mini-seminar on lab animals, but here we are — and hopefully you know more than you did five minutes ago.
Now, let’s look at what these researchers did.
Early Life Adversity: Effect on Brain Function
To simulate the effect of adversity during human infancy in the rodent model, researchers did something remarkably simple. Beginning two days after birth, they restricted the amount of bedding and nesting material available to the experimental (ELA) group of rodents but left the control group with a standard amount of bedding and nesting material. This is called the limited bedding and nesting (LBN) model of early adversity. Researchers maintained the LBN state in the experimental group until eight days after birth, a period analogous to human infancy, then restored the bedding and nesting material to the same state as the control group.
The research team then performed a series of behavioral tests — called an operant conditioning protocol — to simulate acquisition of self-administration, extinction of self-administration, and reinstatement of self-administration. These states are considered analogous developing addiction, ceasing use of the addictive substance, and relapse.
The drug they used was heroin.
Here’s what they found:
· The ELA group and the control group acquired heroin self-administration (became addicted) at the same rate.
· The ELA group resisted extinction of heroin self-administration (kept seeking heroin) for significantly longer than the control group.
· The ELA group re-acquired heroin self-administration more quickly than the control group.
· The ELA group displayed greater preference for highly palatable food, such as M&Ms, than the control group, even when they had to work harder (i.e. perform more operant tasks) to receive M&Ms than they did to receive regular chow pellets.
I’ll translate all that, in case the jargon makes it unclear.
Lab rats exposed to trauma during infancy (the ELA group) did not become addicted to heroin more quickly or more readily than the control group. The ELA group did, however, keep seeking heroin longer than the control group, and when given the opportunity, became addicted again more quickly than the control group. The ELA group also — and this may be the most interesting part of the study — showed a significant preference for more rewarding foods (M&Ms) than for regular food pellets, even when forced to go to great lengths to receive the rewarding food.
That last piece is interesting: it demonstrates that something about early life adversity alters brain chemistry and function to the point that an individual will seek pleasurable experiences over typical experiences regardless of the extra effort required.
Implications for Treatment
The direct link between early trauma and adult addiction goes further back than I imagined. According to the data in this study, it may go all the way back to infancy. Study author Dr. Stephen Mahler, professor of neurobiology at the University of California, Irvine, is convinced it does.
Here’s what he said in a recent interview in Science Daily:
“Our work creates, for the first time, a direct causal link between early life adversity and opioid addiction vulnerability. This is key to the development of predictive biomarkers and possible prevention strategies aimed at addressing the growing opioid abuse epidemic.”
That’s a big step. It means the next step is for researchers to look for those “predictive biomarkers” in the brain regions known to be negatively impacted by toxic stress — read early life adversity — such as the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. I’ll be ready to read and learn from those studies as soon as they’re published.
For now, I can say with higher scientific certainty to my suffering early treatment patients that “you are not a bad person, your brain has been damaged causing you to have symptoms that lead to addiction.”
I also can tell them that I know how to help heal the damaged part of the brain and strengthen the front part of the brain that leads to recovery from addiction. When patients understand their disorder more completely, we can work together to design a course of treatment that works best for them.
Now that is something of true value.