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  • Writer's pictureLachlan

What Really Causes Depression

Let’s start with the usual clinical definition: depression is persistent feelings of sadness, hopelessness, and loss of interest in activities. It can show up with physical symptoms such as fatigue, chronic pain, headaches, digestive issues, and more. To be diagnosed, symptoms must be present for at least 2 weeks and cause significant distress or impairment.

Despite the fact that we only have one label for it, depression can actually present very differently in different people. Some have the classic mood symptoms of sadness and hopelessness, whereas others can’t identify any mood changes per se, but have loss of interest, “deactivation” (oversleep, disengagement), or they may exhibit severe avoidant or escapist behaviour, and irritability. Still others feel numb altogether. Also, depression can come with varying degrees of anxiety as a side kick, as well as other mood/behaviour changes.

The Serotonin Myth

For a long time, the most commonly cited explanation for major depression was that there is not enough of the neurotransmitter serotonin, and to a lesser degree, dopamine and norepinephrine, in the brain. This explanation was born out of experiments in the ‘50s that showed that some depressed patients benefited from drugs designed to treat tuberculosis that also happened to affect some neurotransmitters (López-Muñoz & Alamo, 2009, Whitaker, 2010). This association was taken as proof that depression is caused by low serotonin, but this has never actually been proven.

Serotonin and other neurotransmitters were originally pinned as the therapeutic targets for relieving depression when increasing their levels only ever proved to be helpful to some people. This unreliable response to antidepressant medication is still not well understood.

Today, there is a movement of physicians and advocates that promote alternatives to antidepressant medications. Their main message is that neurotransmitters themselves are not best therapeutic target to actually treat depression (Brogan, 2014; Brookshire, 2018; Hasler, 2010), and that using antidepressant medications aren’t solving the issue, they are simply covering it up. They explain that founding a medical theory on such sparse correlative evidence is like saying that headaches are caused by a lack of Advil.

If Not Serotonin, Then What?

Even if antidepressants are helpful to some people, the whole theory begs the question: why would serotonin (or other molecules) be low in the first place? And if it’s not only neurotransmitters that are implicated, what makes other systems go awry and produce depressive symptoms?

Thanks to recent research, the known world of “depressive causes” has now blown wide open. We are starting to understand the many interconnected pieces that range far beyond the brain, and in fact, include the gut, the immune system, and the external environment. The research group Hasler et. al. list the current theorized broad categories of causes:

  • Inflammation in the brain

  • Psychosocial stress (situational stress, grief, difficult life events and relationships, coping mechanisms, trauma)

  • Stress hormones (disruptions in normal cortisol rhythms and other hormones)

  • Neurotransmitters (including serotonin, norepinephrine, dopamine, glutamate, and GABA)

  • Neurocircuitry (how things are “wired” together through habitually coupled actions, behaviours, and thoughts)

  • Neurotrophic factors (which parts of the brain are stimulated for growth and activity with BDNF and other molecules, and which areas of the brain aren’t?)

  • Circadian rhythms (sleep cycles, melatonin impairment, and associated hormones)

The authors go on to say that because all theories of depression seem to only be partly true for some people, it doesn’t make sense to have a single, unified hypothesis of what causes depression; there are sub-types that behave and respond differently. They add, “treatments, including psychological and biological approaches, should be tailored for individual patients and disease states”.  

Physical-Medical Causes

In addition to the above list, I would add another category: medical conditions that present as depression. While not the most common cause of low mood, medical illnesses must be explored and ruled out.

These conditions below can show up looking like exactly like depression. Even if they’re not the main cause, these certainly contribute to feeling low, and can block recovery:

  • Thyroid conditions (low or even high thyroid activity can result in anxiety and low mood)

  • Hormonal imbalances (almost every single reproductive hormone can cause depression when in a deficiency state, and others when in excess, or out of balance with other hormones)

  • Inflammation (new research is showing depression can be a symptom of both isolated brain inflammation and systemic inflammation)

  • Gut dysbiosis or leaky gut (undigested food due to poor gut bacteria can result in autoimmune activity, sympathetic over-stimulation, and reactive inflammation)

  • Food intolerances (can directly cause psychiatric effects)

  • Nutritional deficiency (many vitamins, minerals, and macronutrients, when in deficiency in the diet, can cause depression and anxiety)

  • Autoimmune conditions (the body’s immune system attacks the body itself, causing deleterious downstream effects, including depression)

  • Sleep issues (sleep loss directly heightens stress response and affects metabolism and neurological reactivity)

  • Specific neurological disorders and other conditions.

These causes can be investigated and either ruled out or treated, when practitioners use a systematic and thorough intake and assessment.

Brain Wiring

We breezed by it earlier, but there was a point made about neurocircuitry as a causal factor for depression. Neurocircuitry refers to how “connected” certain things become in the brain. If we think something negative and feel bad, and then always follow it up with another negative thought, and then another negative thought or behaviour, this negative cycle is likely to repeat itself.

The habitual reactions we have to things that happen in life are like paths worn down in a forest- we are more likely to travel down the same path because we’ve been down it before. The good news is, that these habitual behaviours and reactions can be changed.

Thanks to recent studies, we now know that the brain is “plastic”, meaning it can be changed, and new paths can be molded even into older age, with targeted medical and psychotherapeutic interventions like cognitive behavioural therapy to help change behavioural and biochemical reactivity.

Anxiety As a Cause of Depression?

We talk about depression on its own, but the truth is, it usually presents with at least some degree of anxiety. I often ask my patients what came first, the anxiety or the low mood? Depression can start on its own and cause anxiety, or conversely, depression can be an avoidance behaviour resulting from something else that is unbearable (trauma in the body,

self-loathing, unmanageable anxiety and insecurity). It’s not surprising that they often come together. It’s a good exercise to ask which came first, because it can give some insight into what is the root.

Situational Depression

Of course, sometimes things in life just get so hard that it can feel impossible to see the light. Situational hopelessness can become habitual hopelessness, and in that way, temporary situations feel endless. It’s important to recognize that circumstances play a role in our mood, and that sometimes resources and energy have to go into bettering the situation.

Summing It All Up

After looking at the many causes, and observing that there are in fact several different types of depression, I have concluded that depression is not a disorder, it is a symptom. A symptom of something else going on in the body-mind that requires attention and, quite possibly, love. It’s the body’s check-engine light coming on and telling us we need to look into it and see what is happening.

When treating the symptom of depression, I work with patients to (1) establish the foundations of health through food, movement, and sleep; (2) explore and either rule out or treat biological causes; (3) look at current life circumstances and assess if they can be changed, even if only slowly, to allow for more growth, joy, excitement, less stress, etc; (4) look at psychology and personal history to understand “wiring”, habitual tendencies, trauma, and beliefs.

While it may be daunting to think there are so many things that can cause or contribute to depression, I see it as the opposite: it’s liberating to know that there are many avenues that we can work on to make improvements in your mental health. The first step is acknowledging that there is more to it than brain chemistry, although that plays a part. Your best approach is to work on this with a team of practitioners, including a good therapist and doctor that are willing to do the investigative work with you and help you walk the path to recovery.



López-Muñoz, F., & Alamo, C. (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Current pharmaceutical design15(14), 1563-1586.

Brogan, K. (2014). Depression: it’s not your serotonin. Mad In America Editorials.

Brookshire, B. (2018) If low serotonin levels aren't responsible for depression, what is? The Guardian, Neurotic Physiology.

Hasler, G. (2010). Pathophysiology of depression: do we have any solid evidence of interest to clinicians?. World Psychiatry9(3), 155-161.

Whitaker, R. (2010). Anatomy of an epidemic. Crown Publishing Group.

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