Researchers studied genetic traits of depression in more than 14,000 people

The core experiences of depression—changes in energy levels, activity, thinking, and mood—have been described for more than 10,000 years. The word "depression" has been used for about 350 years.

Given such a long history, it may be surprising that experts still agree on what depression is, how to define it, and what causes it.

Many experts agree that depression is not a single phenomenon. This is a large group of diseases with different causes and mechanisms. This makes it difficult to choose the best treatment for each person.

Reactive and endogenous depression

One approach is to look for subtypes of depression and see if different treatments are appropriate for them. One example is the difference between “reactive” and “endogenous” depression.

Reactive depression (also considered social or psychological depression) occurs in response to stressful life events, such as an attack or the loss of a loved one—an understandable reaction to an external trigger.

Endogenous depression (also considered biological or genetic depression) is thought to be caused by internal factors such as genes or brain chemistry.

Many mental health professionals accept this division. 

However, we believe that this approach is too simplistic.

Although stressful life events and genes can individually contribute to the development of depression, they also interact to increase the risk of depression. It has been proven that there is a genetic component in the predisposition to stress. Some genes influence aspects such as personality, others influence how we interact with our environment.

Our research and its results

Our team decided to examine the role of genes and stressors to test whether classifying depression as reactive or endogenous actually makes sense.

In the Australian Genetic Study of Depression, published in the journal of Molecular Psychiatry, people with depression completed questionnaires about stressful life events. We analyzed DNA from their saliva samples to calculate their genetic risk of developing mental disorders.

Our question was simple: Does genetic risk for depression, bipolar disorder, schizophrenia, ADHD, anxiety, and neuroticism (personality traits) influence the level of exposure to stressful life events?

You may wonder why calculate the genetic risk of mental disorders in people who already have depression. Every person has genetic variants associated with mental disorders. Some have more, some have less. Even people with depression may have a low genetic risk of developing it. These people may have developed depression due to other reasons.

We examined genetic risk for conditions other than depression for several reasons. First, genetic variants associated with depression overlap with variants associated with other mental disorders. Second, two people with depression may have completely different genetic variants. Therefore, we decided to investigate a wide range of genetic variants.

If the subtypes of reactive and endogenous depression make sense, we would expect people with a low genetic component of depression (the reactive group) to report more stressful events. Conversely, people with a high genetic component (endogenous group) will report fewer stressful events.

But after studying more than 14,000 people with depression, we found the opposite.

We found that people with a higher genetic risk for depression, anxiety, ADHD or schizophrenia report more stressors.

Assaults with a gun, sexual abuse, accidents, legal and financial problems, and childhood abuse and neglect were more common in people with a high genetic risk for depression, anxiety, ADHD, or schizophrenia.

These associations were not significantly affected by age, gender, or family relationships. We did not control for other factors that may influence these associations, such as socioeconomic status. We also relied on people's memories of the past, which may not be accurate.

How do genes play their role?

Genetic risk for mental disorders changes people's sensitivity to the environment.

Imagine two people, one with a high genetic risk of depression, the other with a low one. Both lose their jobs. A genetically vulnerable person perceives job loss as a threat to his self-esteem and social status. This is a feeling of shame and despair. He cannot bring himself to look for another job for fear of losing it. For another, losing their job has less to do with themselves and more to do with the company. The two people internalize the event differently and remember it differently.

Genetic risk for mental disorders can also make it more likely that people will end up in environments where bad things happen. For example, a higher genetic risk for depression can affect self-esteem, making people more likely to get into dysfunctional relationships that then go poorly.

What does our study mean for depression? First, it confirms that genes and environment are not independent. Genes influence the environment we find ourselves in and what happens next. Genes also influence how we respond to these events.

Second, our study does not support the distinction between reactive and endogenous depression. Genes and environment have a complex interaction. Most cases of depression are a mixture of genetics, biology and stressors.

Third, people with depression who seem to have a stronger genetic component to their depression report that their lives are marked by more severe stressors.

Clinically, therefore, people with higher genetic vulnerabilities may benefit from training in specific stress management techniques. This may help some people reduce their likelihood of developing depression in the first place. It may also help some people with depression reduce their ongoing exposure to stressors.