Understanding depression: a letter from Science to Society

Think you know what depression is about? Think twice.

Depression. A feeling of sadness, a state of the mind, a mental disorder. We tend to think we know all too well what depression is. But do we, really?

I am sure that during your life you have had some experience, either directly or indirectly, with this dark companion of the human psyche. Or, if you have not, chances are you will have it at some point. The World Health Organization calculates that around 12% of the population in most countries will have at least one episode of clinical depression during their lifetimes. A percentage that is steadily increasing with every new survey, and a growing burden for the lives of millions of people and their communities.

At this point of the introduction, health organizations, governmental departments and many clinicians and researchers would report in economic numbers and figures how heavy this burden is for our societies. But as I think that treating people as if they were money is one of the fundamental reasons why depression is on the rise, I will not even bother referring to those cold statistics in this article. Depression generates immense suffering to the person afflicted and to their immediate environment. And that should be reason enough for wanting to do more research on its neurobiology and for finding better treatments. Full stop.

Depression is a highly debilitating mental disorder that persists for extensive periods of time, and is characterized by low mood but also by an additional wide range of symptoms.

When we talk about depression, I mean what in psychiatry is termed as major depressive disorder. Not the very transient –and healthy– feeling of sadness that comes together with the usual unfortunate events that happen in daily life, from which we are able to recover and go through without too much trouble. We are talking about a debilitating mental disorder that persists for extensive periods of time and is characterized by low mood, but also many other possible symptoms like changes in appetite or sleep patterns, anhedonia, social withdrawal, constant fatigue, difficulty thinking and making decisions, poor memory and even thoughts of suicide.

In addition to mortality directly caused by suicide (up to 15% of severe cases), depressed patients are also more likely to develop complications like cardiovascular disease and type 2 diabetes, and to die from myocardial infarct. Concurrence with addictive or anxiety disorders is also not uncommon.

So, if anyone had any doubts, hopefully now they see that a low Sunday evening mood or being sad because nobody likes their posts on Facebook is actually quite far from the clinical definition of depression.

“OK, we can easily agree on that”, you may think. “But now tell me: What does really cause depression? And how does it do it? Why do some people seem more susceptible than others to getting depressed?” Well, those are all very good points, my dear reader. Let me try to satisfy a bit of your eager curiosity with some of the facts Neuroscience has learnt from depression.

Please note that I will not be dealing with the pharmacology of depression in this article. But if you are interested, maybe you want to check this other article on a promising new treatment for depression, where I also discuss about other commonly used antidepressant drugs:

Right now, there is general agreement among the scientific community that depression arises from the complex interaction of environment and genes. Put in the simplest way possible, the cause of depression is stress and its action on our biology, filtered by our genetic predisposition. This action results in the characteristic neurobiology of the disease, that will in turn cause the depressive symptoms we can observe in behaviour.

Various hypotheses seek to explain the neurobiology of depression. From among them, the most remarkable are: increased neuroinflammation, decreased neurotrophic support and hyperactivation of the stress response axis. Without forgetting the famous and slightly old-fashioned brain chemical imbalance (of monoamines like serotonin)!

There are more theories regarding the neurobiology of depression, but it is not my objective to discuss them thoroughly at this moment. Maybe in another article? You tell me!

Independently of the hypothesis that appeals to you the most, stress mainly acts inducing epigenetic modifications. These alterations affect the normal function of neurons, their wiring and the usual activity of diverse neuronal networks. Altogether, that results in the abnormal brain dynamics and behavioural changes we see in depressed people.

Most of the times, depression comes after an intense psychosocial stress. But it can also appear with milder psychological stress if it is sustained for long enough. These forms of stress can be very diverse in nature, but have very similar results. For example, they can go from parental neglect and childhood trauma to being bullied by a psychopathic boss. Also losing a loved one, suffering from a chronic medical condition or lacking social and emotional support will typically lead to a common set of depressive symptoms.

Whichever the case may be, the grounds for the first major depressive episode are often laid well in advance.

Starting before birth and up to early adulthood, a critical window of opportunity is temporarily open: a time when we are most susceptible to everything surrounding us. The younger we are, the more receptive our brains to our immediate environment. From an evolutionary perspective, that is the way to approximately predict how our future will be. And also to adapt to it as well as possible in order to increase our chances of survival and reproduction. Most young children are not only more capable of learning new languages than adults. They are also a lot better at learning how to interact with other people and how to process and manage emotions. This is because of something we call neuroplasticity, or the capacity of neurons to be more flexible and better adapt to the input coming from the environment, that we receive through our senses. Depending on the activity of our neurons during early life, our neuronal networks are shaped, defining how we see and feel the world, and what the basis of our personality will be.

As newborn babies, we had the highest number of neurons and synapses we would get in our whole lives. No massive neuronal birth happens in the adult human brain, only moderate neurogenesis is allowed and in very restricted locations. Then, from all that “planned excess” of neurons, we selected those that would come with us to adulthood by actively stimulating them with a pragmatic use-it-or-lose-it policy. The neurons that are not activated properly by the environment will generally not be selected, and progressively die away. This is the way your nervous system has to adapt to the environment where you are born, while avoiding an excess of noise that would lead to inefficiency in neuronal communication and behavioral malfunction. Too many or too few synapses, and serious mental disorders like autism or schizophrenia appear. That will probably give you an idea of how important this neuronal fine-tuning is.

If exposed to intense stress during the early stages of our existence, the vulnerability to develop depression is hardwired into our brains.

As we turn into adults, we still retain a bit of neuroplastic potential (otherwise we could not learn anything new!). But it is definitely more reduced than in early development, and thus is considerably more difficult and time-consuming to introduce changes in our neuronal circuitry and behavior. As a result, if exposed to emotionally challenging situations during your first years on this world, depression –or rather vulnerability to develop it– can be hardwired into your brain. And that vulnerability will probably accompany you for the rest of your life.

I can imagine that you will be wondering: “And how is depression supposed to help me in better adapting to the environment?!”. Again, good question my avid reader. And definitely not an obvious one. The answer, however, may be simpler than you expect:

Evolution does not give a fuck about our wellbeing as individuals. It just cares about you existing and reproducing, under whatever condition.

And depression may have been very useful for this purpose through the history of our species.

Imagine a time when leaving the comfort of your lair was a threat for your survival. OK, you do not have to imagine too hard. A normal day in one of our urban concrete jungles may still be full of dangers. But think of an even more threatening situation. Like in the case of a ruthless war. Or living in a small settlement in the lion-ridden African savannah, thousands of years ago. Or during a harsh winter in the Scandinavian peninsula. You get the point.

In such a case, when staying in your safe isolation was more advantageous for your survival than venturing out, depression could have actually been a mechanism of defense. Of course, provided you had somehow gathered the supplies needed to survive or had someone bringing them for you (empathy be blessed!). You may have survived in a pitiful state of body and mind, but survived nonetheless.

And with survival, sooner or later, often comes reproduction. And with reproduction comes inheritance, both in the genetic and cultural senses of it. This cycle, endlessly repeating itself through generations and generations, got us where we are now. Although we do not need to go to such extreme examples. In the case of a sentimental break-up or when repeatedly being submitted to abuse from a superior at work, depression may allow us to protect ourselves when we are most vulnerable and give us some time to recover. But the problem with this is evident. If we reach a situation where we become hypersensitive to stress and this defensive mechanism is too easily activated without a real need for it, depression brings an unnecessary suffering that is counterproductive for everyone. In that case, we call it a maladaptive response. Or in simpler terms, a disease.

Depression may allow us to protect ourselves in times when we are most vulnerable. But the problem comes when it is activated without need.

Epidemiologic studies point at several gene mutations that may predispose the carriers to develop depression –just as there are other variants that may make individuals more resistant to it–. But it must be stressed here that just as with any other developmental disorder, genetics is not enough to trigger the pathology. The interaction with the environment through nurture and later experiences in life will define the outcome. And just as a person that has high genetic predisposition will develop a higher resilience if raised in a supportive and caring environment, one that lacks the genetic predisposition will easily become vulnerable if growing up in a highly stressful environment. In fact, and perhaps not surprisingly, there is abundant data published showing that lower socioeconomic status is a very good predictor for higher risk of developing mental disorders, and is associated with much higher rates of relapse after treatment than their richer counterparts.

With that in mind, let us get personal here.

If your mother is already worrying with you in her belly about how will she make it to the end of the month with a shit salary, her stress in the form of cortisol will cross the maternofetal barrier in the placenta and start preparing your brain for a hyper-responsiveness to stress later in life. Then, when you are born, chances are that the situation does not improve much, and you find that your parents cannot spend much time with you because they need to work their lives away so you can have a plate of warm food on the table for dinner. It is likely that even when they have the time, they are too tired and unable to provide their child with the high quality parenting needed for a healthy development. Or that their stressful lives translate at home into domestic violence. Possibly, they will also have high tendency to develop dependence on alcohol or any other drugs that can help them relieve the stress. And they will use those drugs knowing that they are only momentarily pleasurable. And despite the fact that they just further disrupt their lives. And even when they also disrupt yours.

If by the time of finishing high school you are in the position of going to university, congratulations! That is already a miracle. But how are you supposed to get in when your parents barely have money to keep themselves well fed? And to be honest, studying without access to the necessary study-materials and support services will not make it any easier. Not to mention that constantly having your attention on the struggle taking place at home does not leave much energy or time for academic curiosity. Getting high grades in such a situation cannot be considered as anything less than an achievement of heroic proportions. Even more so when the psychological consequences of such a hard start begin to arise in the shape of mental disorders, from anxiety and depression to schizophrenia and addiction.

The deduced social implications are painfully stark.

The vicious cycle of poverty perpetuates the suffering and lack of opportunities through generations, as people are not given much chance of breaking free from it. Every human being since birth is potentially valid to perform any kind of task society may have for them. Be it becoming an astronaut, an artist, a farmer, an engineer or a politician. We just need the opportunity to grow up in a healthy environment and learn. And it should be obvious that the support coming from the collective in the form of social policies is of crucial importance for both the individual and society itself. We need to provide everyone with safeguards that prevent mistreatment of any kind. And even more importantly, with top-quality education and healthcare that are free of cost and grant true equal opportunities.

Giving access to a minimum of resources that allows every human being to live with dignity is not only possible, but also an ethical duty. Imagine all the potential talent we are losing that could be working right now on a better future for Humanity. This is not a matter of political ideology, but a matter of deep evolutionary significance.

Society has a responsibility in the physical and mental welfare of its citizens, and that is something that cannot be eluded.

If we have learned something in our history as a species is that for us it is not enough with plain survival. We want to live, and live well, so that we can reach as far as we can and contribute to the development of our communities. We want the next generation to have a better starting point than the one we had. Well, at least some of us have realized that. Others, with a rather more parasitic behavior, continue to egoistically accumulate and waste resources with no regard for any other being or generation but themselves.

In numerous cases the typical symptomatology of depression may be suppressed due to the social stigma associated with mental disorders.

All what we are discussing here is very relevant for the times we are living. In numerous cases of trauma, depression and anxiety, the typical symptomatology may be suppressed due to the social stigma associated with mental disorders. The main way of coping with the suffering that remains for those people is usually through aggressive behavior. This is especially true for males, who out of shame or fear of “showing weakness”, hide their true feelings from the world and from themselves, and may try to compensate by reacting violently to stress. And as you must be well aware, this can lead to dramatic personal and sociopolitical conflicts.

Males especially may try to compensate their emotional repression by reacting aggressively to stress.

In my view, it is remarkably wicked how some influential figures have traditionally taken advantage of the vulnerability of those people. Instead of helping them learn how to cope better with their problems and provide them with social support, they use their fear and frustration to achieve their selfish objectives. And what is even worse, those vulnerable people are usually misled to canalize their anger against other humans, who often enough, are even more vulnerable than them. After all, it may not be a coincidence that in every chance they have, those twisted minds try to perpetuate the state of vulnerability of the majority through cutting on education, healthcare and social services. Cutting on the fair distribution of resources. But that only leads to a very dangerous and unproductive confrontation that can easily turn into an explosion of violence at any moment. And when we are at a point of human history where some of those vicious influential people can get easy access to weapons of mass destruction, neglecting the vulnerabilities of the majority may not be the smartest evolutionary path for our species to take.

We are living in a society that is drifting farther and farther away from our empathic and collaborative nature.

We are currently living in a social construct that rewards psychopathic behavior with increasing amounts of power. We have established a deeply rooted culture of materialistic individualism that dehumanizes its members, slowly wears out their minds and health, and inevitably promotes antisocial conducts. We are living in a society that is drifting farther and farther away from our empathic and collaborative nature.

No wonder depression is on the rise.

Humanity reminds me frequently of a living organism in its function and structure. And what is an organism if not the result of a cooperation among all its constituents for the general interest? It is through that general interest that every cell acquires a purpose and a meaning, and finally achieves its own individual success.

An organism that is at war with itself is a sick organism, and without a remedy, it is destined to die. On the contrary, an organism that is able to work in synchrony, not only lives, but expands its legacy through thousands of generations to come.

When you interact with people out there, you sure have noticed different sensitivities to stress, and sometimes you may even feel tempted to judge them with the reference of your own life experience. If that is your case, let me tell you one thing: Probably, you will never be able to imagine what that person has gone through. What you are seeing is the result of a huge inner struggle that is draining their souls away. And even if they are not consciously aware of what is causing it, they are suffering a great deal. For that precise reason, try to treat everyone fairly, help them if there is something for you to do, and be as nice as you possibly can. We are social animals, and most of the times we just need to find someone to share our life experiences, rest a while from our burdens and feel the support of our communities.

And if you, dear reader, are suffering from depression, I also want to tell you something: Hang in there. I can understand where you are. I can imagine how you feel. But no matter how frightening and dark the night is, hang in there. The light of the sun always comes back. Just hang in there.

If you made it until here, thank you. I know it must have been quite a wild ride. And I also know how valuable your time is. So thank you.

I would like to finish this text sharing some powerful words that a very good friend of mine used to say:

“Always remember that it is not in the calm sea and under the clear sky that one learns how to be a good sailor, but in the most terrifying of storms”.

If you enjoyed this article or thought it was useful, please hit that wonderful ♥ so this information can reach more people! Also, I didn’t want to go full neurobiology on this article, but if you’re interested in the more sciency side of depression, please let me know down in the comments and I will prepare an article reviewing it in much more detail. Questions, suggestions and discussion are always welcome!