What Can Twins Teach Us About How Stress Impacts Health?
We can learn more than we bargained for from “natural experiments.”
Posted Jan 12, 2020
When I was a child, I had a waking fantasy that there was another little girl in the world who was exactly like me—she was my unrecognized identical twin—and everything I did, she did the opposite. If I went right, she went left. If I had pancakes for breakfast, she had eggs (let's save the debate about what the “opposite” of pancakes is for another day…). The point of this fantasy was “What would my life be like if I did B instead of A? Would I turn out the same?” I will leave it to the psychoanalysts to infer what these childhood musings mean clinically, but with the benefit of hindsight, I see them as evidence that I was destined to become an epidemiologist.
The primary framework epidemiology uses to identify causal relationships is called the “counterfactual”—as in what would have happened if what did (in fact) happen had not? In experiments, such as randomized controlled trials, we (the researchers) experimentally manipulate what treatment (or placebo) each participant receives through a process of random assignment. Then we compare the outcomes of the treatment groups. If the outcomes of the groups are different, we infer that this difference is due to the treatment, because the groups were, on balance, similar on all other characteristics. That is, we infer that the people who got Treatment A would have had the same outcome of the group that got the placebo if they, too, had gotten the placebo instead of the treatment.
But many of the types of things epidemiologists think are important to health are not amenable to experimental manipulation. For example, stressful life events. Traumatic and major life events have long been identified as risk factors for mental health outcomes, everything from schizophrenia to substance abuse. Researchers also examine stress as a risk factor for physical health outcomes. Here the explanatory model is still emerging, and there is less consensus as to the exact mechanisms linking trauma and stress to outcomes like heart disease, cancer, and diabetes.
Experiments in animals give us some clues, but part of the issue is that trauma and stress are not something you can investigate in a randomized controlled trial. And because stress and trauma are generally not randomly distributed in the population (the occasional earthquake notwithstanding), it means that whatever factors are correlated with exposure to them may also be correlated with the health outcome of interest.
For example, experiencing trauma in childhood has been associated with risk of cancer in later adulthood. What could explain this? Well, people with a history of trauma are more likely to smoke, and tobacco use is a known cause of many types of cancer. So does trauma cause people to smoke, and then smoking causes cancer? Or is there some other factor that increases both the likelihood someone is exposed to trauma and the likelihood that they smoke—like lower socioeconomic status or genetic liability? Identifying a causal, as opposed to just correlational, relationship in these types of situations is a hotly contested issue in the field.
It is in this context that “natural experiments” come into play. A “natural experiment” is a situation that exists in the world, unintentionally, that somehow separates or cleaves correlated exposures. For example, you may have read the recent news story about the IRS mailing letters reminding people of the fee they would incur if they did not sign up for health insurance under the Affordable Care Act (the so-called Individual Mandate). Except somehow the IRS only mailed this letter to a random set of the people it should have. This allowed researchers to test the effect of being sent a letter (versus not being sent one) on later health outcomes.
A more common kind of “natural experiment” involves identical twins. Identical twins result from a single fertilized egg splitting in two, and as a result these individuals share 100% of their genes. They share the same parents, are the same age, sex, and race/ethnicity, and can generally be conceived as starting life with the same set of assets and liabilities—biological, psychological, and social. When we compare identical twins in terms of their health outcomes, this gives us insight into the ways that external events and exposures—such as stress—contribute to health and disease.
For example, by comparing the health outcomes of twins (e.g., one of whom had a history of depression and the other who did not), researchers have shown that both depression and PTSD increase risk of type 2 diabetes and cardiovascular disease. These findings suggest that the causes of those mental health outcomes—which are primarily driven by exposure to trauma and stress—may also contribute to cardiometabolic health later in life.
This is what we are doing in one of my current studies, which recruited about 50 pairs of identical twins from the Mid-Atlantic Twin Registry, the largest such registry in the United States. We are interested in learning how stress and mental health contribute to risk of type 2 diabetes. We interviewed both members of the twin pair, separately, and asked about a range of traumatic and stressful experiences they may have had—everything from experiencing physical abuse to being fired from a job to the death of a loved one. These types of questions are par for the course in terms of epidemiologic studies of stress and health.
But we also did something different: We asked people to tell us about their “most fulfilling or gratifying” life event, which was followed by a host of questions to help us understand how this experience impacted their life. Interestingly, many people had a hard time coming up with this event, perhaps reflecting our penchant for paying more attention to negative events than to positive ones. However, I will never forget the one interview where the participant had no trouble identifying this event. As soon as I finished reading the question, they immediately responded “Being born a twin.” That is, the most gratifying thing that had ever happened in their life was the accident of their birth. They explained that having a twin meant that they had a built-in partner to weather all the trauma and stress that life threw at them (which had been substantial in their case); it meant that they were never alone; that they were intrinsically understood by another person; that someone always had their back, and that they had theirs; and that their purpose in life was never in question.
I often reflect on the meaning that this “natural experiment” has had on this person’s life, both from the perspective of science and philosophy. As a child, I had assumed that the things that mattered to the outcomes of me and my “imaginary twin” were the choices we made and the experiences we had. It had never occurred to me that the simple presence of another human being in my life could be the map that guides my path.
As I scientist, I know that the counterfactual framework has little to offer when it comes to identifying the causal effect of being understood by another. But as an adult who has weathered many stressful experiences, I fundamentally understand the wisdom of this person’s response.
**UPDATE: For those of you who like a little physics with your metaphysical musings about "What if I did A instead of B...", I recommend listening to this episode of This American Life.
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