Biography of Depression — Part II
Or, does stress cause depression?
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Alright! On to this week’s essay. This is the second part of a two-part essay on depression. Last week we covered what depression feels like. Today we’ll explore what causes depression. It’s about 1,800 words.
Q: why do only some of us get depressed?
The best evidence suggests that depression involves abnormal levels of the neurotransmitters (chemicals that help transmit signals between nerve cells or neurones) norepinephrine, serotonin, and dopamine.
Most of the drugs that lessen depression increase the amount of signalling by these neurotransmitters. One class, called tricyclics, prevents the reuptake of neurotransmitters back into the nerve cells after they have been released. This means that the neurotransmitters stay in the space between the nerve cells (called the synapse) for a longer time, increasing the chances of them binding to their respective receptors and transmitting signals multiple times.
Another class of drugs, called MAO inhibitors, blocks the breakdown of neurotransmitters in the synapse by inhibiting the action of an enzyme called monoamine oxidase (MAO). By preventing the breakdown of neurotransmitters, more of them are available in the synapse to stimulate the receiving nerve cell.
Based on these discoveries, we can draw a simple conclusion: if a drug that increases the levels of certain neurotransmitters such as norepinephrine, serotonin, and dopamine is effective in improving someone’s depression, it suggests that there was an insufficient amount of those neurotransmitters in their brain initially.
Not so fast.
There are two main areas of confusion regarding neurotransmitters in depression. First, it’s unclear whether serotonin, dopamine, or norepinephrine is the primary issue.
Medications like tricyclics and MAO inhibitors affect all three systems, making it hard to pinpoint the critical one. Second, scientists have conflicting views on whether there is too little or too much neurotransmitter activity involved in depression, and both sides have compelling evidence. Despite this, serotonin receives more attention, while dopamine is given relatively less emphasis.
Serotonin is specifically thought to have something to do with those ceaseless dark thoughts in depression. Part of the reason is because antidepressant drugs (technically, Selective Serotonin Reuptake Inhibitors or SSRIs) are often effective on people with obsessive-compulsive disorder. In the depressive’s case, it is the obsessive sense of failure, of doom, of despair, while in the latter case, it can be obsessive worries that you left the gas on at home when you left, that your hands are dirty and need to be washed, and so on.
Some diseases can also cause depression, especially those that involve overactivation of the immune system (for example, chronic infections, or an autoimmune disease where the immune system has accidentally activated and is attacking some part of your body).
This is mostly because sometimes cytokines (molecular messengers of the immune system) can get to the brain and they can destabilise norepinephrine, dopamine, and serotonin systems.
Not only that, people who secrete too little thyroid hormone can also develop major depressions and, when depressed, can be atypically resistant to antidepressant drugs working. This is particularly important because many people, seemingly with depressions of a purely psychiatric nature, turn out to have thyroid disease.
And then there’s the most obvious reason: stress. When people go through many stressful situations in life, they are more likely to experience a major depression. Similarly, when someone is already in their first major depression, they are more likely to have recently faced significant stress.
Obviously, not everyone who experiences stressful situations becomes depressed, but stress can both trigger and be a result of depression. For instance, if you have two or three major episodes of depression, you’re not statistically more likely to experience another one compared to others. However, once you reach around the fourth episode, a pattern emerges where depressive episodes occur regardless of external stressors affecting you.
If you repteadly stress a rat in the lab, it becomes anhedonic. Specifically, it takes a stronger electrical current than normal in the rat’s pleasure pathways to activate a sense of pleasure. This means, the threshold for perceiving pleasure has been raised, just as in a depressive.
Apart from stress, grief is another major cause of depression. In his classic essay Mourning and Melancholia, Sigmund Freud mentions what the two have in common: the loss of a loved object — usually a person or a goal or an ideal.
In Freud’s formulation, in every loving relationship there is some ambivalence — elements of hatred as well as love. In the case of a small, reactive depression (such as mourning) you are able to deal with that ambivalence in a healthy manner: you lose, you grieve, and then you recover.
In the case of a major melancholic depression, you become obsessed with the ambivalence — the simultaneity, the irreconcilable nature of the intense love alongside the intense hatred. Melancholia — a major depression — Freud theorised, is the internal conflict generated by this ambivalence.
It also explains the intensity of the guilt often experienced in major depression. If you truly harboured intense anger toward the person along with love, in the aftermath of your loss there must be some facet of you that is celebrating, alongside the grieving. “He’s gone; that’s terrible but…thank god, I can finally live, I can finally grow up, no more of this or that.” Inevitably, a metaphorical instant later, there must come a paralysing belief that you have become a horrible monster to feel any sense of relief or pleasure at a time like this, causing incapacitating guilt.
This theory also explains the tendency of major depressives in such circumstances to, oddly, begin to take on some of the traits of the lost loved/hated one — and not just any traits, but invariably the ones that the survivor found most irritating.
Psychodynamically, this is wonderfully logical. By taking on a trait, you are being loyal to your lost, beloved opponent. By picking an irritating trait, you are still trying to convince the world you were right to be irritated — you see how you hate it when I do it; can you imagine what it was like to have to put up with that for years?
And by picking a trait that, most of all, you find irritating, you are not only still trying to score points in your argument with the departed, but you are punishing yourself for arguing as well. Out of the Freudian school of thought has come one of the more apt descriptions of depression: “aggression turned inward.”
Depression is psychologically exhausting. You feel hopeless. There’s no end in sight. Even if there were, your vision is too distorted to see it. You have developed a form of learned helplessness.
When subjected to repeated uncontrollable stressors, a rat undergoes a remarkable transformation. In a simple learning task, where the floor is divided into two halves and electric shocks are delivered to one half with a signal beforehand, a normal rat quickly adapts and avoids the electrified side. However, a rat previously exposed to chronic stressors becomes helpless and fails to learn the task. It is a powerful demonstration of how prolonged, unpredictable adversity can shape our ability to cope and learn.
One might wonder whether the helplessness is induced by the physical stress of receiving the shocks or, instead, the psychological stressor of having no control over or capacity to predict the shocks. It is the latter.
If you take a pair of rats such that one rat gets shocked under conditions marked by predictability and a certain degree of control, the other rat gets the identical pattern of shocks, but without the control or predictability, only the latter rat becomes helpless.
This phenomenon is called learned helplessness. Animals suffering from learned helplessness share many psychological features with depressed humans. Such animals have a motivational problem — one of the reasons they are helpless is that they often do not even attempt a coping response when they are in a new situation. This is quite similar to the depressed person who doesn’t even try the simplest task that could improve their life. “I’m too tired. It seems overwhelming to take on something like that. It’s not going to work anyway.”
Growing up, if a teacher or a loved one at a critical point of a child’s emotional development, frequently exposes them to their own specialised uncontrollable stressors, children may grow up with distorted beliefs about what they cannot learn or ways in which they are unlikely to be loved.
In one chilling demonstration, some psychologists studied a bunch of school kids with severe reading problems. Were they intellectually incapable of reading? Apparently not. The psychologists circumvented the students’ resistance to learning to read by teaching them Chinese characters instead. Within hours they were capable of reading more complex symbolic sentences than they could in English. The children had apparently been previously taught all too well that reading English was beyond their ability.
In short, stress, particularly in the form of extremes of lack of control and outlets, causes an array of deleterious changes in a person. Cognitively, this involves a distorted belief that there is no control or outlets in any circumstance — learned helplessness. On the mindset level, there is anhedonia; behaviourally, there is psychomotor retardation. On the neurochemical level, there are likely disruptions of serotonin, norepinephrine, and dopamine signalling. Physiologically, there are alterations in appetite, sleep patterns, among other things, and then there’s also sensitivity of the glucocorticoid system to feedback regulation.
We collectively call this array of changes a major depression. But the most basic question remains: Why do only some of us get depressed?
A better way to answer this would be to invert the question and ask: How is it that any of us manage to avoid getting depressed? All things considered, this can be an awful world, and at times it must seem miraculous that any of us resist despair.
What occurs in reality is something like this: a major stressor comes along and produces some of the neurochemical changes of depression. The more prior history of stress you have, especially early in life, the less of a stressor it takes to produce neurochemical changes that can lead to depression.
Take a sufficiently severe stressor and virtually all of us will fall into despair. No degree of neurochemical recovery mechanisms can maintain your equilibrium in the face of some of the nightmares that life can produce.
Conversely, if you have a life sufficiently free of stress, even with a genetic predisposition, you may be safe — a bomb poses no danger if it is never armed.
In between those two extremes, it is the interaction between the ambiguous experiences that life throws at us and the biology of our vulnerabilities and resiliencies that determines which of us fall prey to this awful disease.
Today I Learned
Your brain is not for thinking.
Once upon a time, Earth was inhabited by creatures that lacked the complex brains we possess today. Among these creatures was the amphioxus, a worm-like being that thrived about 550 million years ago. Its existence was simple, driven solely by basic instincts for survival. With no eyes, limited sensory abilities, and a rudimentary nervous system, the amphioxus was essentially a “stomach on a stick.”
However, about 550 million years ago, as the Earth entered the Cambrian period, a significant evolutionary shift occurred. Hunting emerged as a purposeful activity, marking a crucial step towards the development of more complex brains.
The appearance of predators transformed the world into a competitive and dangerous place, prompting both predators and prey to evolve more sophisticated sensory systems. While the amphioxus could barely differentiate light from dark, newer creatures acquired the ability to see and sense their environment with greater acuity.
With heightened senses, the fundamental question of survival became: “Is that creature a potential meal or a threat?” Creatures that could better perceive and evaluate their surroundings had a higher chance of survival. Unlike the amphioxus, these new creatures possessed the capacity to sense their environment and react accordingly.
Alongside enhanced sensory abilities, the creatures of the Cambrian period also evolved more advanced motor systems, enabling deliberate movements that suited their environment.
Efficient movement became crucial for survival. Those who moved too slowly risked losing their prey, while those who wasted energy fleeing nonexistent threats depleted their resources. Energy efficiency became a key factor in determining who thrived and who perished.
Just as managing finances involves careful budgeting, managing a body necessitates anticipating its needs and efficiently allocating resources. Allostasis, the process of predicting and preparing for the body’s requirements before they arise, emerged as a vital mechanism for survival.
Creatures relied on their past experiences to inform their present actions, repeating successful strategies and learning from mistakes. Even single-celled organisms demonstrated predictive planning. Although the exact mechanisms behind this ability remain a mystery, it underscores the importance of prediction in shaping survival strategies.
As creatures continued to evolve, their bodies became more complex, requiring intricate internal systems to maintain balance. The rudimentary body-budgeting cells present in the amphioxus evolved into increasingly sophisticated brains. These brains were responsible for supervising numerous bodily functions, regulating hormones, digestion, immune responses, and much more. The brain had become a command centre, overseeing the coordination of countless processes in a highly complex world.
Reflecting upon this evolutionary journey, we are led to ask: Why did a brain like ours evolve? While evolution itself does not act with purpose, we can identify the brain’s most important function. It is not rationality, emotion, or creativity.
The brain’s primary responsibility is to control our bodies, to manage allostasis effectively, and predict energy needs before they arise. It continuously invests our energy with the hope of obtaining essential resources such as food, shelter, and protection — fundamental prerequisites for passing on our genes to future generations.
In essence, our brain’s most crucial role is not solely focused on cognitive functions but rather on running our intricately complex bodies. Nevertheless, our brains do facilitate a multitude of mental capacities, including thoughts, emotions, and imagination. But every experience we have, from memories to dreams, is intricately linked to the central mission of maintaining our body’s balance and ensuring our survival.
Timeless Insight
The Great Depression was the longest and deepest economic downturn in the history of the industrialised world. It began in 1929 and lasted until the late 1930s. The depression was caused by a number of factors, including the stock market crash of 1929, the collapse of the banking system, and a drought that led to widespread crop failures. The depression caused widespread unemployment, poverty, and homelessness.
The dot-com bubble was a period of rapid economic growth in the late 1990s and early 2000s, driven by the rise of the internet. The bubble burst in 2000, and the resulting recession was the longest since the Great Depression. The recession caused widespread job losses and financial hardship.
In both of these cases, the booms lasted for several years, and the busts were correspondingly severe. This is because the longer a boom lasts, the more people become complacent and take on more risk. When the bust finally comes, it can be very disruptive.
People have short memories and poor imaginations, so the most common economic forecast of what will happen next is extrapolating whatever happened last. This is why bear markets breed pessimists and bull markets breed optimists. People tend to see the world in straight lines, but markets are cyclical and unpredictable.
This is what keeps things interesting. The economy is a complex system, and it is impossible to predict with certainty what will happen next. However, by understanding the forces that drive the economy, we can make better decisions about how to manage our finances and our businesses.
What I’m Reading
You don’t have an inner lizard or an emotional beast-brain. There is no such thing as a limbic system dedicated to emotions. And your misnamed neocortex is not a new part; many other vertebrates grow the same neurons that, in some animals, organize into a cerebral cortex if key stages run for long enough. Anything you read or hear that proclaims the human neocortex, cerebral cortex, or prefrontal cortex to be the root of rationality, or says that the frontal lobe regulates so-called emotional brain areas to keep irrational behavior in check, is simply outdated or woefully incomplete. The triune brain idea and its epic battle between emotion, instinct, and rationality is a modern myth.”
— Lisa Feldman Barrett, Seven and a Half Lessons About the Brain
Tiny Thought
We spent so much effort trying to improve our income, skills, and ability to forecast the future — all good stuff worthy of our attention. But on the other side there’s almost a complete ignorance of expectations, especially managing them with as much effort as we put into changing our circumstances.
Before You Go…
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I’ll see you next Sunday,
Abhishek 👋
PS: All typos are intentional and I take no responsibility whatsoever! 😬