"Behind the scenes" of adolescent depression

One in seven adolescents worldwide experienced mental health difficulties in 2019, with depression being one of the leading causes of illness and disability, and the third leading cause of death among adolescents worldwide.


As much as 90% of the world child and adolescent population come from low-and-middle-income countries (LMICs) and nearly 80% of the suicides globally come from LMICs, bearing in mind that many of these are left not recorded.



These are striking statistics, yet many of these young people are left undiagnosed, without the help they need. The lack of awareness, persistence of stigma, and the lack of resources are some of the reasons we find ourselves in this heart-breaking scenario. But it’s not only that. It’s also the lack of knowledge. In order to help, we need to understand what exactly we are treating.


Depression is a multi-layered condition and, as such, it develops as consequence of many factors — nature and nurture being equally important. Most evidence on what happens in depression, from the biological point of view, comes from the studies in adults. When depressed, our bodies are more likely to produce stress hormones such as cortisol or noradrenaline. Signs of chronic inflammation or changes in how different areas of the brain work (some areas showing less activity and some being overly active) are also commonly seen. A range of environmental risk factors, such as domestic violence, or experience of abuse and neglect in childhood, may also contribute to increased vulnerability of becoming depressed later in life.



So, how do the pieces of the puzzle come together, and when is the best time to intervene? I asked myself this question some years ago, when I started my journey in the science of depression. I am a research psychologist and my PhD focused on depression and inflammation. Currently, I work on Identifying Depression Early in Adolescence (IDEA) project at King’s College London, which is part of the Brighter Futures programme launched by the MQ: Transforming Mental Health Charity. The IDEA project aims to identify universal risk factors for depression in adolescents and young people, with a particular focus on LMIC, including Brazil, Nepal and Nigeria, which you can read more about in one of our previous blogs published by my colleague. In this blog, I will share with you, what I have learnt so far about the development of depression and how much we know about depression in adolescence.


Depression “behind the scenes”


Starting from the beginning: if exposure to stress can increase risk for depression, then something must be happening biologically in response to stress.


Indeed, when we are faced with a stressful situation, we release a hormone called cortisol, which helps us respond appropriately to the demands of the situation. This is a very clever and efficient system that our bodies have designed, and a very healthy one at that. Right up until it’s not…


When we are exposed to chronic stress which repeatedly outgrows our coping strategies, we might end up in a situation where cortisol is no longer capable of doing its job. We become desensitized to its helpful action. Instead, we end up with high levels of cortisol flowing through our bodies which is something we see often in adults and adolescents with depression.


Next, is our immune system, and more specifically inflammation. Think about the last time you had the flu and what your mood was like. The chances are, it wasn’t very upbeat, and that’s because your immune system was activated to fight the virus. The state of chronic, low grade inflammation is one of the biological changes often seen in depression, as well as in people who have experienced early life stress.


Lastly, studies looking at how our brains function reveal that when we are depressed, certain areas of our brain are less, while others are more active compared with individuals who are not depressed. For example, the area of the brain responsible for processing emotions — the limbic area — tends to be overly active in people with depression whereas an area where higher executive functioning happens such as decision making, planning, social and emotional regulation — the prefrontal cortex — becomes less active.


So, how is it all linked together?


In a nutshell, early life stress, can push our bodies to manifest higher levels of cortisol, leading to higher inflammation which in turn, can affect our brain functioning. More recently, studies in animals have shown that being exposed to chronic early life stress, leads to higher inflammation through the release of a different stress hormone — noradrenaline — which is part of the “fight or flight” response.

To answer my second question, “when is the best time to intervene?”, I would say: as early as possible. It is becoming clear that a large proportion of people develop depression in the first decades of their lives. If we were to develop effective prevention strategies, adolescence would be a window of opportunity to do that.


Very recently, I reviewed a worldwide literature looking at the association between biological markers and environmental stress risk factors for adolescent depression. My first reaction was, wow, there are only a handful of studies available and only two from LMICs!!! This was also my first finding.


My second finding was that for the most part, these studies seem to reflect what we already learnt in adult depression, i.e., higher levels of inflammation and changes in the activity in different areas of the brain. What’s interesting is that these biological changes are particularly relevant in the context of early life stress.


There are two ways these mechanisms appear to work. One way suggests that biological vulnerabilities (e.g., increased inflammation) may only lead to the development of depression within stressful environmental contexts, i.e., experience of early life adversity, but not in contexts of low stress — in science, we call it a moderation effect. Another way implies that early life stress can modify our biology, e.g., how our brains function, which in turn leads to depression — a mediation effect. All in all, these studies seem to suggest that early life adversity and the immune system or changes in how the brain works are closely intertwined with each other, in the leading up to depression in adolescence.


My third finding was that we desperately need more research, particularly in LMIC settings, to understand the science of adolescent depression but also to achieve the greatest public health impact. At the moment, we don’t know whether our findings are universal or specific to high-income-countries, as these populations are heavily overrepresented in the research.


To wrap it up, I think that having done the worldwide literature review highlighted to me how much still needs to be done in understanding adolescent depression. But this was a good starting point in trying to paint a wider picture of what happens “behind the scenes” when we fall depressed at young age.


I also hope that bridging the knowledge gap will bring us closer to identifying those at-risk, working towards raising awareness, reducing stigma, and increasing treatment accessibility, in particular in LMIC settings. If you would like to read more about it, my research findings have been recently published in The Journal of Psychiatric Research.


Lastly, I would like to say that although I have been talking about the “path to depression” and how it can manifest in biological changes, it is only one side of the story. The more positive side of this story is that those biological changes can be reversible and that nothing is set in stone, and I will talk about it in my next blog. Stay tuned!