Decoding Depression: Bridging Genes, Behaviors, and Environments

• People genetically predisposed to depression are also more likely to have experienced negative life events.
• The genes associated with depression may not just “cause” depression; they might also increase the likelihood that people will engage in behaviors or encounter situations that further increase the risk of depression.
• Environmental influences, such as socioeconomic status and gender, are crucial to understanding depression.

What Causes Depression?

We know depression is the result of genetic and environmental factors. But how does this combination work, exactly?

This is the question taken up by Tamkinat Rauf of the University of Wisconsin and Jeremy Freese of Stanford University in their recent article in Social Science & Medicine. Their evidence suggests that genes may not just “cause” depression directly, but rather that genes predispose people to experience the negative life experiences that can often induce depression.

Read on to learn more about Rauf and Freese’s findings, and what you can do if you or someone you know is suffering from depression.

Background

The old “nature versus nurture” debate is obsolete. It’s now understood that genetic and environmental factors are intertwined in complex ways. Genes influence how we act in certain environments; and, at the same time, our environment can cause certain genetic factors to “switch on” or “switch off.” There’s now a huge literature in both the natural and social sciences devoted to understanding how this works.

Depression is a great example of this complex interplay:

• On one hand, studies, particularly those involving twins, suggest that genetics play a major role in depression, accounting for over half of the variation in some cases.
• On the other hand, research has consistently shown that environmental stressors are significant triggers for depression. Negative experiences can induce depressive behaviors or feelings of insecurity that last beyond the event.

We know which genes are associated with depression, but we don’t know how or to what extent they “cause” it.

• We know there’s no one “depression gene.” It’s a large group of genes that collectively affect the risk of depression.
• In scientific literature, an array of genes and how they relate to some outcome (such as depressive symptoms) is called a polygenic index (PGI).
• We know the PGI for depression. But how these genes actually “cause” depression is still unknown.

We also know that certain types of adversity tend to be hereditary. Many experiences can cause depression, but the scientific literature makes a distinction between two types of negative experiences:

• “Independent” events that happen to you beyond your control, such as disability, sexual abuse, or the death of a loved one
• “Dependent” experiences that are–at least somewhat–under your behavioral control, such as dropping out of college, divorce, or substance abuse.
• We know that these “dependent” experiences tend to have a strong genetic component, and therefore tend to be passed down in families.

This led Rauf and Freese to propose a new hypothesis. What if some people are genetically more likely to wind up experiencing those “dependent” negative experiences, and it is through that increased likelihood of certain experiences that they also end up with an increased likelihood of depression? In other words, what if those with a PGI for depression tend to behave in certain ways that put them in certain negative situations, and that’s what leads to their increased risk of depression?

The Study

The study uses data from two primary sources: the National Longitudinal Study of Adolescent to Adult Health (Add Health), and the Wisconsin Longitudinal Study (WLS), both of which have genetic data and detailed information on adverse life experiences. The analysis is based on the most recent survey waves from both datasets.

• Add Health focuses on individuals who were in grades 7–12 in the U.S. in 1994-95, and includes respondents aged 33-44.
• WLS covers a sample of Wisconsin high school graduates from 1957, and includes individuals aged 45-92.
• This diverse age range allows for observing adversities across different life stages.

They also conducted a separate survey to understand how people attribute life experiences to individual behavior. This involved 160 American adults rating the perceived behavioral dependence of 27 adversities, which were drawn from established inventories like the PERI Life Events Scale and Adverse Childhood Experiences inventory. The adverse events are:

The analysis proceeded through several steps:

1. First, the study looked at the correlation between those 27 adverse experiences and the presence of depressive symptoms, which were measured using different versions of the Center for Epidemiological Studies-Depression (CES-D) scale in both Add Health and WLS.
2. Then, they used the genetic data and a PGI for depressive symptoms (based on a sample of 1.3 million individuals) to predict the odds that a particular subject would encounter adversities, given their PGI.
3. Finally, they compared their predictions to the actual data. How well does someone’s depressive PGI actually predict if they will experience these negative events–especially those “dependent” events that are somewhat under their behavioral control?

Rauf and Freese controlled for socioeconomic background, sex, age, and ancestry to ensure these variables did not skew the results.

Findings

There are two main questions to be answered. First, is Rauf and Freese’s hypothesis that the genetic profile for depression might predict who is more likely to experience adversity supported by the evidence? The answer is yes.

• Unsurprisingly, the more adversities someone experiences, the more depressive symptoms they report. This was the case in both datasets used, and was especially the case for recent experiences (like losing a job) compared to something that happened long ago.
• Rauf and Freese found a strong link between the genetic risk of depression (measured by PGI) and the chance of facing various hard times. This points to genetics playing a role in the kinds of challenges people might face in their lives.
• Even when they controlled for indirect genetic effects by comparing siblings only, PGI was still a significant predictor of some adversities. This means that the PGI might be capturing more than just family-genetic influences.

The study also shows that a person’s social class and gender have a big impact on the risk of facing these challenges, emphasizing the role of both genetic and environmental factors.

The second big question has to do with “independent” and “dependent” types of adversity. If Rauf and Freese’s hypothesis is correct, we’d expect a stronger correlation between a person’s genetic profile (as measured by PGI) and the likelihood of experiencing those dependent types of adversity (as measured by their survey examining how much control people have over each of those 27 negative life events) than the likelihood of experiencing those independent events they have little or no control over.

This was in fact the case–although with an important caveat:

• The r coefficient, which measures the extent to which two variables are correlated linearly (0 = no correlation, 1 = perfect correlation) was 0.33. This indicates a moderate correlation, and is quite strong compared to many social science studies. (Some significant studies I have seen have an r-value of 0.2).
• The p-value, which measures how likely the analysis would have yielded these results randomly (0 = could not have happened randomly, 1 = easily could have happened randomly) was 0.09. In other words, there’s about a 9 percent chance this correlation happened randomly, rather than measuring the actual phenomenon Rauf and Freese were looking for.
• Conventionally, in the social sciences, we like to see a p-value of 0.05 or lower in order to declare a result “statistically significant.” Rauf and Freese argue, however, that because they were only measuring 27 adverse events–a very small number, statistically–that “this remains suggestive evidence that the genetic burden of depression is more strongly associated with adversities regarded as being influenced by a person’s behavior.”

In the end, perhaps the greatest contribution of this study is to showcase just how messy and complicated the effects of genes, behaviors, and environments are in manifesting depression:

• For example, the research suggested that adversities could mediate the relationship between genetic risk and depression. This means that experiencing adversities might partly explain why people with a higher genetic risk for depression actually develop depressive symptoms.
• At the same time, previous depressive symptoms, particularly those immediately before an adversity, were also found to be partly responsible for the relationship between genetic risk and experiencing adversities. This indicates that sometimes the experience of depressive symptoms can lead to adverse life events.

Overall, the study paints a picture of a complex interaction between genetics, life experiences, and depressive symptoms over a person’s life. It suggests that both direct genetic effects and the environments shaped by parental genetics play a role in an individual’s life experiences and mental health. Further research is definitely needed to help untangle these myriad factors.

What to Do If You or a Loved One Is Struggling with Depression

You can’t change your genes or the negative experiences you’ve suffered through. But depression is a highly treatable disorder if addressed correctly. If you think you or a loved one are depressed, try the following interventions:

1. Seek Professional Help: Consulting a mental health professional such as a psychiatrist, psychologist, or therapist is crucial. They can provide a diagnosis, therapy, and medication if needed. Cognitive Behavioral Therapy (CBT) and other therapeutic approaches have proven effective in treating depression.
2. Medication: If prescribed by a healthcare professional, antidepressant medications can be an important part of treatment. They can help correct chemical imbalances in the brain that contribute to depression.
3. Support System: Lean on friends, family, or support groups. Sharing feelings with someone trusted can be therapeutic and provide a sense of belonging and understanding. Support groups, either in-person or online, can connect individuals with others who have similar experiences.
4. Healthy Lifestyle Choices: Regular exercise, a balanced diet, and adequate sleep can significantly impact mental health. Exercise, in particular, releases endorphins which have mood-boosting properties. Aim for a routine that includes these elements.
5. Mindfulness and Relaxation Techniques: Practices like meditation, yoga, and deep breathing exercises can reduce stress and improve mood. These techniques help in staying present and reducing negative thought patterns.
6. Set Realistic Goals: Depression can make tasks seem daunting. Setting small, achievable goals can provide a sense of accomplishment and purpose. Breaking larger tasks into smaller steps can make them more manageable.
7. Avoid Alcohol and Drugs: These substances can worsen depression and interfere with medications. It’s important to avoid them or seek help if struggling with substance abuse.

Have you or someone you know experienced depression? What do you think about the idea that genes may predispose people to behaviors or situations that increase the risk of depression? Share your opinions in the comments.

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