Depression: genes, stressors and the reactive versus endogenous divide

The central features of depression - shifts in energy, activity, thought and mood - have been recognised for more than 10,000 years. The term ‘depression’ itself has been in use for roughly 350 years.

Despite that extensive history, specialists still disagree about what depression is, how it should be defined and what causes it.

However, many experts concur that depression is not a single condition. Instead, it is a broad family of illnesses with varying causes and underlying mechanisms. That variety can make it difficult to select the most suitable treatment for an individual.

Reactive versus endogenous depression

One approach involves looking for depression sub-types and assessing whether they respond more effectively to different treatments. A commonly proposed distinction is between ‘reactive’ and ‘endogenous’ depression.

Reactive depression, sometimes described as social or psychological depression, is thought to arise after stressful life events. Being assaulted or bereaved, for instance, may prompt an understandable response to an external event.

By contrast, endogenous depression, also referred to as biological or genetic depression, is suggested to result from internal factors, such as genes or brain chemistry.

This form of classification is accepted by many mental-health clinicians, and you may have encountered it online.

But we believe the distinction is far too simplistic.

Stressful life events and genes can each play a part in causing depression, but they also interact in ways that raise a person’s likelihood of developing it. Evidence also indicates that exposure to stressors has a genetic element. Certain genes influence characteristics including personality, while others shape how we engage with our surroundings.

What we investigated and what we found

Our team examined the contributions of genes and stressors to determine whether dividing depression into reactive and endogenous forms was valid.

Participants in the Australian Genetics of Depression Study who had depression completed questionnaires about their exposure to stressful life events. We then analysed DNA from saliva samples to estimate their genetic risk for mental disorders.

We asked a straightforward question: does genetic risk for depression, bipolar disorder, schizophrenia, ADHD, anxiety and neuroticism - a personality trait - affect the stressful life events people report experiencing?

You might ask why we calculated genetic risk for mental disorders among people who already had depression. Everyone carries genetic variants associated with mental disorders, although some people have more than others. Even someone with depression may have a low genetic risk for the condition. Their particular depression may instead have developed through another combination of causes.

We considered genetic risk for conditions besides depression for two reasons. Firstly, genetic variants connected with depression overlap with variants associated with other mental disorders. Secondly, two people with depression can carry entirely different genetic variants. We therefore took a broad approach, examining a wider range of genetic variants linked to mental disorders.

If reactive and endogenous depression were valid sub-types, we would expect people whose depression had a lower genetic component - the reactive group - to report more stressful life events. Those with a greater genetic component - the endogenous group - would be expected to report fewer such events.

Yet, after examining more than 14,000 people with depression, we found the reverse.

People at greater genetic risk of depression, anxiety, ADHD or schizophrenia reported having encountered more stressors.

Assault with a weapon, sexual assault, accidents, legal and financial difficulties, and childhood abuse and neglect were all more frequent among people with higher genetic risk for depression, anxiety, ADHD or schizophrenia.

These links were not substantially affected by participants’ age, sex or family relationships. We did not assess other factors that could affect these associations, including socioeconomic status. We also depended on people’s recollections of past events, which may be inaccurate.

How genes can play a part

Genetic risk for mental disorders can alter people’s sensitivity to their environment.

Consider two people: one has a high genetic risk for depression and the other a low risk. Both lose their jobs. The person with greater genetic vulnerability may experience redundancy as a threat to their self-worth and social standing, producing feelings of shame and despair. Fearful of losing another role, they may be unable to bring themselves to seek work. For the other person, losing the job may feel less personal and more attributable to the company. They internalise and remember the same event in different ways.

Genetic risk for mental disorders may also increase the chance of finding oneself in environments where harmful events occur. For example, a higher genetic risk for depression could affect self-worth, making someone more likely to enter dysfunctional relationships that subsequently go badly.

What the study means for depression

Firstly, the findings confirm that genes and environments are not separate influences. Genes affect the environments we enter and what happens in them. They also shape our responses to those experiences.

Secondly, our results do not support a division between reactive and endogenous depression. Genes and environments interact in complex ways. In most cases, depression involves a combination of genetics, biology and stressors.

Thirdly, people with depression who seem to have a stronger genetic contribution to their condition report lives marked by more serious stressors.

In clinical terms, people with greater genetic vulnerability may benefit from learning particular stress-management techniques. This could help some people lower their chance of developing depression in the first place. It may also enable some people with depression to reduce their continuing exposure to stressors.

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If this article has raised concerns for you, or you are worried about someone you know, contact Samaritans on 116 123.

Jacob Crouse, Research Fellow in Youth Mental Health, Brain and Mind Centre, University of Sydney, and Ian Hickie, Co-Director, Health and Policy, Brain and Mind Centre, University of Sydney

This article is republished from The Conversation under a Creative Commons licence. Read the original article.