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Depression affects more than 320 million people worldwide or about 17% of the world’s population.  It is a condition that is highly burdensome and recurrent, often striking for the first time during adolescence or young adulthood. 

Given its scope, global burden, and connection to negative outcomes – including suicide – imagine how many lives could be improved and even saved if there were ways to prevent the onset of this devastating condition. 

Although there is a lot we are still learning about the causes of depression, what’s clear is that depression is the product of a complex interaction between our genes and our environment.

How do genes come into play?

For decades, scientists have known that genetic factors play a role in shaping risk for depression. For instance, studies of families have revealed that individuals with depression were 3 times more likely than those without depression to have a family history of the disorder.  

In the past decade, efforts have been made to better understand what specific genes might be involved in shaping vulnerability to depression.  Much of these efforts have been focused on identifying the genetic variants that occur more frequently among people with depression (compared to people without depression), using a method called genome-wide association studies (GWAS).   

In the largest GWAS study to date, which included around 135,000 individuals with depression and 345,000 without depression, an international team of researchers from the Psychiatric Genomics Consortium (PGC) identified 44 genetic variants associated with increased likelihood of depression.

These variants were located in or near genes that regulate multiple biological functions, such as inflammation. Importantly, this and other GWAS studies also make clear that there is no single gene that determines someone’s risk for depression.  Instead, many genes work together to influence someone’s likelihood of developing depression.

Despite all this evidence supporting the role of genes in shaping depression, we also know that genes alone cannot fully predict whether someone will develop depression. Even people who carry all of the risk genes identified by GWAS may never develop depression. In fact, a recent study showed that compared to those with the lowest genetic susceptibility for major depression, people with the highest genetic susceptibility only had 2.4 times higher risk for depression. So, what explains why this happens?

The environment also plays a role.

A range of non-genetic or environmental risk factors have been implicated in depression, including:

·      early life adversities

·      negative life events

·      low socioeconomic status

·      severe physical illnesses

Of these experiences, our research group (called “The Dunn Lab”) at the Massachusetts General Hospital focuses primarily on childhood adversities because every year, more than 3 million children report some form of child maltreatment (e.g., physical abuse, neglect, etc.) in the US, and childhood could be an important time for early intervention. The damaging effects of early life traumatic experiences also last well beyond childhood, spanning into adolescence and even adulthood.

For example, it may not be that surprising to hear that children or adolescence who experience maltreatment are more likely to experience depression.  But studies have also found that people who experienced child maltreatment were more likely to develop depression for the first time even as an adult.  

However, like genetics, the environments we live in and the experiences we have are only part of the equation. Researchers have found that almost half all children with a history of child abuse or neglect do not develop adult psychiatric disorders.

Further, if you could create a world where no one was ever exposed to child adversity, this would only remove one out of five cases of depression. This raises an important question: Why is it that two individuals exposed to the same adversity respond so differently?

Because our health is a product of a complex interaction between genes and the environment.

Clearly neither nature nor nurture alone can explain why an individual would develop depression. Rather, a combination of the two determines how individuals will react to different stressors in life. Indeed, several studies have shown that the effects of stressful life events and childhood abuse on risk for depression differs by a person’s genetic susceptibility to depression. That is, those who have more depression ‘risk’ genes and experience a lot of stressors are more likely to develop depression than those who carry the same risk genes but do not experience any stressors.                                             

 Modified figure from Peyrot et al. (Br J Psychiatry, 2014)

Modified figure from Peyrot et al. (Br J Psychiatry, 2014)

What does this all mean?

The days of thinking about “nature versus nurture” are long gone.  We now know that genes and the environment work together to shape not only risk for depression, but many of our behaviors.  As more and more genes involved in shaping depression vulnerability are identified, we can combine this data with information about people’s experiences to identify populations who are most at risk and who could be targeted for depression prevention strategies. Furthermore, understanding how social and biological factors interact to affect our risk for depression can help us develop personalized treatments, aimed at modifying our environment or biology.

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