How are you? ’Busy!’ is a common reply. For many young people, stress is a part of everyday life, and sometimes they face additional adversity. While some people are able to pull through, it overwhelms others. What role does variation in brain structure play in these situations?
 
Many young people in the Netherlands nowadays experience stress, burn-out and depression. Within our society, there is a growing realization that a lot of young people experience great pressure, and that this can adversely affect mental health. Furthermore, psychological problems are more often addressed by the media. In 2018, a research survey from Dutch current affairs program EenVandaag conducted among youth showed that three out of ten young people (aged between 16 and 34 years) had experienced depressive feelings in the past two years.^[1] According to the survey, these feelings have a major impact on daily life: many of these young people find it difficult to enjoy life, experience depressive feelings every day, feel lonely, have trouble sleeping and have suicidal thoughts.^[1] On top of that, many also feel too ashamed to talk about these negative feelings.
 
In early 2018, the Dutch government launched a campaign to open up a discussion about mental health.^[2][3] Furthermore, they decided to conduct a large-scale research study on the mental health of Dutch youth, on which the Netherlands National Institute for Public Health and the Environment published a report in May of 2019.^[4] This report indicates that psychological complaints among youth have increased, nowadays affecting around 10 to 15 percent of Dutch young people. Depression is relatively most prevalent in the age category 18 to 24, as one in fifteen young people from this group met the criteria for Major Depressive Disorder.^[5]
 
Why is the mental health of young people under so much pressure? And why do some experience a depression, whereas others show resilience? Can we identify young people with an increased risk of depression and support them in order to prevent the onset of illness?

Depression among young people is not only a problem in Dutch society.

Disruptions in the brain
That young people are particularly vulnerable to mental illness, including depression, is also supported by international research.^[5][6] As such, depression among young people is not only a problem in Dutch society. Why is it that young people are particularly vulnerable to depression?
 
Potentially, there is an important role for the structure of the brain. It is well-established that the youth brain is in continuous development, on average until the age of twenty-five.^[7] This brain development parallels increases in cognitive capacity.^[8][9] For example, risk-taking behavior in adolescents gradually decreases when the prefrontal cortex develops, as they can better predict the consequences of their actions and have increased control over their behavior.^[10]
 
Precisely because this brain development is so important, minor disruptions in the process could potentially explain why young people are at a greater risk of depression onset. For my master thesis, I therefore investigated the rate of structural development in the youth brain. When this structural brain development shows a deceleration or acceleration compared to normative trajectories, this could potentially induce an imbalance in the brain, which may increase vulnerability to depression.
 
Real age versus ‘brain age’
In my project, I investigated whether the rate of structural brain development is related to the onset of mood disorder, including depression. To answer this question I analyzed a dataset from a study in which more than two hundred healthy young people were followed for up to six years to see if they would experience a mood disorder.^[11] Half of this group had a direct relative with bipolar disorder^[*] and was therefore at an increased risk of mood disorder.
 
As part of the study, the participants also had two MRI sessions to obtain a structural brain scan or ‘picture of the brain’, once at the beginning of the study and once more two years later. For my project I applied machine learning to these brain scans. In machine learning, a computer algorithm searches for a pattern in the data. When the algorithm has learned this pattern it will create a model, which can then be applied to new data. In my master thesis, the algorithm learned the relationship between global brain structure and age. This way I could estimate the ‘brain age’ for each participant for both timepoints of the study. Subsequently, I compared this ‘brain age’ to the real, chronological age of the participant, and this gave insight into the development of each individual’s brain over time.
 
The analysis of the difference between ‘brain age’ and chronological age suggested that young people at familial risk for mood disorder who also developed a mood disorder, showed slower development of brain structure than young people with or without familial risk who remained mentally healthy.
 
So the cause of mood disorders is in the brain?
Slower structural development across the brain was thus found to be associated with onset of mood disorder in young people with familial risk. This finding is a first indication that decelerated global structural changes in youth brains may contribute to vulnerability for depression. For this reason, such study results are important to gain a better understanding of mood disorder onset in young people.
 
In the future, would it be possible to predict if a young person will experience onset of depression based on a structural brain scan? Looking at the individual trajectories of brain development, it appears that there are large individual differences within groups. Therefore, the difference found at group level cannot produce good predictions on the individual level. For this reason, it is unlikely that it will be possible to predict who will experience psychiatric problems based solely on a brain scan.

Mental conditions are extremely complex and likely arise from the interaction between a variety of factors.

The real cause of depression
So what is the utility of these study findings? To answer this question, it is important to look beyond the brain, or even beyond the human body. Research shows that mental conditions are extremely complex. They likely arise from the interaction between many factors, including stress from the environment, personality, the way of dealing with problems (also known as coping), the availability of a support network, genetic predisposition, and other biological factors, including brain structure. This is called the biopsychosocial model , which can help to explain why some young people experience depression, whereas others show greater resilience to adversity. At the moment it is largely unclear which factors play an important role and how these interact with each other. Researchers try to map risk factors that increase vulnerability to mental disorders, as well as factors that promote resilience.
 
By conducting more research, researchers hope to improve our understanding of disorders like depression. To this aim, research studies in which healthy young people are followed for multiple years to see if they develop a mental disorder or remain in good mental health are particularly useful, because they allow the identification of factors that precede the onset of mental problems. This unlike studies that include participants with an established diagnosis, as it is often impossible to know the direction of causality in such studies.
 
In the future, it will hopefully be possible to make accurate predictions on a personal level by taking into account all factors from the biopsychosocial model of depression. For at-risk youth, additional support or preventive treatment could help to limit the number of risk factors and increase resilience, for example by teaching them efficient ways of coping with problems and by helping to expand their social support network.
 
Editor: Stephanie Bosschaert
 

Laura de Nooij

Laura de Nooij (1994) works as a researcher at the Division of Psychiatry at the University of Edinburgh, where she investigates depression using big data. Following this master thesis project (conducted in Edinburgh under supervision of Dr Heather Whalley) she graduated in 2018 from the Research Master’s program Psychology at the University of Amsterdam. A manuscript about this research is currently being evaluated for publication in a scientific journal. Laura is mainly interested in the biological processes causing psychiatric disorders and how we can tailor treatment to the individual.