3 Causes Of Depression You Probably Didn’t Know

causes of depression

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“Family History of Depression Alters Brain’s Response to Reward and Risk. National Institute of Mental Health. National Institutes of Health.”

It is a challenge to admit you may be mentally ill. While mental disorders may be looked down upon by the less informed or misinformed, the only way forward is to recognize them as medical conditions, just like a broken arm or cancer.

Depression, one such mental disorder, affects more than 300 million people of all ages worldwide.[ref]Depression. World Health Organization.[/ref] Moreover, it is not just a one-time occurrence like chicken pox. Up to 65% of individuals have recurring episodes of depression.[ref]Slavich, George M., and Michael R. Irwin. “From stress to inflammation and major depressive disorder: A social signal transduction theory of depression.” Psychological bulletin 140, no. 3 (2014): 774.[/ref]


Depression is 1.7 times more common in women than men.

Nearly 1 in 4 women and 1 in 6 men experience depression during their lifetime.[ref]Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V. Age differences in major depression: Results from the National Comorbidity Survey Replication (NCS-R) Psychological Medicine. 2010;40:225–237.[/ref] The higher incidence of depression in women[ref]Albert, Paul R. “Why is depression more prevalent in women?.” Journal of psychiatry & neuroscience: JPN 40, no. 4 (2015): 219.[/ref] has been attributed to differences in sex hormones, physical strength, personality traits, and exposure to stressors.[ref]Verma, Rohit, Yatan Pal Singh Balhara, and Chandra Shekhar Gupta. “Gender differences in stress response: Role of developmental and biological determinants.” Industrial psychiatry journal 20, no. 1 (2011): 4.[/ref][ref]Elliott, Marta. “Gender differences in causes of depression.” Women & Health 33, no. 3-4 (2001): 183-198.[/ref]


Depression is different from being depressed. It is not a synonym for sadness.

It is completely normal to feel blue. Feeling sad and grieving, say due to loss of a loved one or pet, a financial crisis, or a relationship failure is us being human. But when circumstances change for the better and things begins to look up for us again, we indulge and recover – maybe slowly but we do.

Clinical depression, on the other hand, prolongs that period of sadness, not allowing you to recognize a positive change in your circumstances. It robs you of your ability to enjoy the pleasures of life, physically slowing you down and interfering with your focus, sleep, memory, appetite, sex drive, and even the basic will to live.[ref]Older Adults and Depression. National Institute of Mental Health. National Institutes of Health.[/ref] These reactions are not the part-and-parcel-of-life kind. Things you normally find enjoyable will attract no attention from you, and you will feel blue for 2 weeks at a stretch or even longer.


Depression Is A Prolonged Adaptive Response

Causes Of Depression

Depression is not what evolution intended for us. We were not supposed to be stressed for long periods of time.


Our bodies are evolutionarily designed to adapt to stressful situations through the fight or flight response.[ref]Ilardi, Stephen. Depression is a disease of civilization. TEDxEmory.[/ref][ref]Stress System Malfunction Could Lead to Serious, Life Threatening Disease. Eunice Kennedy Shriver National Institute of Child Health and Human Development. National Institutes of Health. 2002.[/ref] This response focuses all of our energy at alleviating a threat, actual or potential, for a few seconds, minutes, or in extreme cases, a few hours. This response was particularly useful to our hunter-gatherer ancestors when they had to protect themselves and their loved ones from predators or the brutal forces of nature.

While we are no longer hunter-gatherers, this primal coping system has persisted as we continue to face our own versions of modern-day dangers and stress. However, the adaptive response tends to be prolonged in certain people more than required, implanting the roots of depression.[ref]Gilbert, Paul, Jean Gilbert, and Chris Irons. “Life events, entrapments and arrested anger in depression.” Journal of affective disorders 79, no. 1 (2004): 149-160.[/ref]


Causes Of Depression

People suffering from depression take 10 years on an average to ask for help.

The causes of depression are not as clear-cut as the causes for other more physically visible diseases like arthritis. Being a mental illness, depression is difficult to diagnose or detect by observing patterns, as the test subjects are people with different personalities. This also brings to light the fact that people suffering from depression take about 10 years on an average to seek help.[ref]Ilardi, Stephen. Depression is a disease of civilization. TEDxEmory.[/ref] Fewer subjects to study translates to compromised, partial understanding of this very complex epidemic.


Even within the scientific community, different schools of thought – from geneticists to neuropsychiatrists to behavior analysts – have emerged. And while these different perspectives aim at understanding the same phenomenon, their approaches are often different, controversial even.

Besides this, a major problem in researching a mental illness is the dilemma between cause and effect. While it is more convenient for pharmacists to accept biochemical abnormalities as the first-level triggers, it is yet to be decided whether biochemical changes are in reality effects and not causes of psychological stressors or whether they are a combination of both.


Some individuals are more vulnerable to suffering from depression than others because of gene-environment interactions[ref]Steimer, Thierry. “The biology of fear-and anxiety-related behaviors.” Dialogues in clinical neuroscience 4 (2002): 231-250.[/ref]:

  • During their development in the womb
  • During life experiences

Digging through all the information available, 3 key players in depression emerge:

  1. Genetics
  2. Neural networks
  3. Psychosocial stress

1. Genetics

Some people are born susceptible to depression, maybe because it runs in the family or because their mothers were depressed when carrying them. Besides this genetic predisposition, turning on and off of certain genes can also make you more susceptible to depression. One such gene is GATA1.

Genetic Predisposition

We are not always lucky enough to shield ourselves from depression. Some things are out of our control and are dependent on heredity or the way our brains developed in the womb.

  • Smaller Areas Of The Brain

If you come from a family with a history of depression, you have high chances of suffering from it, too.

Individuals who are born with a smaller than average hippocampus or amygdala (emotion areas) or prefrontal cortex (personality development area) are more susceptible to suffering from depression.[ref]aan het Rot, Marije, Sanjay J. Mathew, and Dennis S. Charney. “Neurobiological mechanisms in major depressive disorder.” Canadian Medical Association Journal 180, no. 3 (2009): 305-313.[/ref][ref]Schatzberg, Alan. Major Depression: Causes or Effects? The American Journal Of Psychiatry.[/ref] Smaller volumes may mean fewer neurotransmitter sites and lesser neural signaling. Depression may even further downsize these parts of the brain, causing brain damage.

Brain structure is largely dependent on inherited genes. So, individuals who have family members (immediate family or close relatives) with a history of depression are more vulnerable to suffering from the disease than others.[ref]Causes of clinical depression. National Health Service.[/ref][ref]Family History of Depression Alters Brain’s Response to Reward and Risk. National Institute of Mental Health. National Institutes of Health.[ref] Also, they are likely to suffer from depression at a younger age.[ref]Tozzi, F., I. Prokopenko, J. D. Perry, J. L. Kennedy, A. D. McCarthy, F. Holsboer, W. Berrettini, L. T. Middleton, H. D. Chilcoat, and P. Muglia. “Family history of depression is associated with younger age of onset in patients with recurrent depression.” Psychological medicine 38, no. 05 (2008): 641-649.[/ref]

Having said that, because depression depends on external factors as well, life situations and personal factors can counteract this shortcoming.

  • Prenatal Exposure To Maternal Depression

If your mother was depressed when you were in the womb, your chances of suffering from depression are higher.

An expectant mother, particularly in her third trimester, can influence her growing child’s ability to cope with stress. A pregnant woman under stress is likely to give birth to a child who is less capable of coping with stress later in life and has a higher tendency to suffer from depression.[ref]Oberlander, Tim F., Joanne Weinberg, Michael Papsdorf, Ruth Grunau, Shaila Misri, and Angela M. Devlin. “Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses.” Epigenetics 3, no. 2 (2008): 97-106.[/ref]

GATA1 Gene Overexpression

GATA1 is a genetic switch that interferes with nerve signals in the brain. Fewer nerve signals may cause depression.

From the diverse kinds of personalities of depressed people, it is easy to guess that not one but many genes are responsible for depression. Of the many, one gene called GATA1 has been identified.

Building on past findings that a smaller prefrontal cortex (the personality center in the front part of the brain) is one factor responsible for depression, researchers have identified one gene, GATA1, which plays a role. GATA1 is a protein that serves as a genetic switch (transcription factor). It is capable of turning other genes on or off, including those of neurotransmitters, synaptic molecules, and nerve cell receptors. Because of this, GATA1 overexpression causes significant neural disconnects in the brain.[ref]Genetic Switch Involved in Depression. NIH Research Matters. National Institutes of Health.[/ref] Fewer connections between different parts of the brain is a trigger for depression.

2. Neural Networks

A brain that is unable to fire enough and correct nerve signals is vulnerable to depression. A major cause for these abnormal or depleted neural networks (that is, a series of interconnected neurons) is low levels of neurotransmitters. It is intriguing how our diet, thyroid gland, and regular medications can deplete our neurotransmitter levels.

Low Levels Of Neurotransmitters: Serotonin, Dopamine, And Noradrenaline

Time and again, the scientific community has suggested that depression boils down to deficiencies in certain neurotransmitters in the spaces between brain cells. Apart from serotonin that has drawn maximum attention, neurotransmitters like dopamine, noradrenaline, and gamma-aminobutyric acid (GABA) have been implicated in this highly complex mental disorder.[ref]Rao, TS Sathyanarayana, M. R. Asha, B. N. Ramesh, and KS Jagannatha Rao. “Understanding nutrition, depression and mental illnesses.” Indian journal of psychiatry 50, no. 2 (2008): 77.[/ref]

One-third of those treated with antidepressants do not improve, while most others show some improvement but remain depressed.[ref]Hal Arkowitz, Scott O. Lilienfeld.Facts and Fictions in Mental Health. John Wiley & Sons. 2017.[/ref]

Most of these claims seem to stem from the positive effects of antidepressants, which are nothing but neurotransmitter supplements, on patients suffering from depression. However, antidepressants have not been able to cure all depression patients. So, depression may not always be caused by neurotransmitter depletion, at least not entirely.

Further, counseling alone has been able to successfully treat several cases of depression. This poses an underlying suggestiveness that maybe emotions play an equal part as chemicals within our cells – chemicals may be effects and not the actual causes. This offers hope to people preferring to cure themselves naturally.

  • Nutritional Deficiencies: Omega-3s, Proteins, Vitamins, And Minerals

As expected, diet inevitably affects how our bodies function. This effect has been found to extend to our minds as well. Lack of certain nutrients in our diet can be a potential cause for depression, possibly by affecting the level of neurotransmitters in the brain.[ref]Janicak PG, Lipinski , Davis JM, Comaty JE, Waternaux C, Cohen B, et al. S-adenosylmethionine in depression: A literature Review and preliminary report. Ala J Med Sci. 1988;25:306–13.[/ref]

Omega-3s: More than 60% of the brain is fat. It needs fats to function optimally. It has, thus, been suggested that deficiency in omega-3 fatty acids can cause depression.[ref]Martins, Julian G. “EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials.” Journal of the American College of Nutrition 28, no. 5 (2009): 525-542.[/ref][ref]Shepherd, J. “Lipids in health and disease.” (2004): 1051-1056.[/ref] Since fish is a prime source of omega-3s, eating more fish may help protect you from depression.

Proteins: Proteins are made up of amino acids which are building blocks for many neurotransmitters in the brain – for instance, tyrosine for dopamine and tryptophan for serotonin. Understanding the crucial nature of neurotransmitter imbalances, it makes sense that protein deficiency is capable of putting you at a higher risk of depression.[ref]Janicak PG, Lipinski , Davis JM, Comaty JE, Waternaux C, Cohen B, et al. S-adenosylmethionine in depression: A literature Review and preliminary report. Ala J Med Sci. 1988;25:306–13.[/ref]

B-complex vitamins and minerals: Deficiencies in B-complex vitamins (B2, B6, B12, and folate) and minerals like calcium, iodine, and iron have been implicated as triggers of depression.

The theory that nutritional deficiencies cause depression has been extended to loss of appetite in old age.[ref]Janicak PG, Lipinski , Davis JM, Comaty JE, Waternaux C, Cohen B, et al. S-adenosylmethionine in depression: A literature Review and preliminary report. Ala J Med Sci. 1988;25:306–13.[/ref] Lesser food intake during old age may result in inadequate nutrient intake and a higher risk for depression.

  • Hypothyroidism

Insufficient production of thyroid hormones has often been implicated as a cause for depression, assuming it somehow influences serotonin levels. While thyroid hormones have proven to be a beneficial addition to antidepressants in the treatment of depression, further studies are required to establish a link between the thyroid gland and depression.[ref]Dayan, Colin M., and Vijay Panicker. “Hypothyroidism and depression.” European thyroid journal 2, no. 3 (2013): 168-179.[/ref][ref]Hage, Mirella P., and Sami T. Azar. “The link between thyroid function and depression.” Journal of thyroid research 2012 (2011).[/ref]

  • Side Effects Of Certain Medications

Medications taken as part of treatments of other conditions may cause depression as a side effect. Drug-induced depression may be caused by certain groups of drugs – corticosteroids (prescribed for rashes and asthma), varenicline (nicotine addiction), progesterone inserts (infertility), and finasteride (hair loss and enlarged prostate).[ref]Rogers, Donald, and Ronald Pies. “General medical drugs associated with depression.” Psychiatry (Edgmont) 5, no. 12 (2008): 28-41.[/ref]

3. Psychosocial Stress

When stress triggers don’t go away and you continue to be affected, you are at a higher risk of depression.

Coming back to the fight or flight response, there are 2 glands in the brain – the hypothalamus and the pituitary – and 1 in the kidneys, the adrenal gland, which form a feedback loop called the HPA axis (hypothalamic-pituitary-adrenal axis). This axis controls our reactions to stressful situations.[ref]Slavich, George M., and Michael R. Irwin. “From stress to inflammation and major depressive disorder: A social signal transduction theory of depression.” Psychological bulletin 140, no. 3 (2014): 774.[/ref]

When faced with any form of danger or stress, be it a kitchen fire or a public speech, the HPA axis is activated and the adrenal gland increases production of the stress hormone cortisol. Cortisol gives you all the energy you need to face your fears and eliminate the threat. Cortisol is also anti-inflammatory, keeping your immune system in check and protecting you from getting diseases that involve excess inflammation.

When the trigger for stress persists for a long time, our bodies get desensitized to high levels of cortisol. Inflammatory proteins are now no longer suppressed because of cortisol insensitivity and, hence, increase in production. This is our body’s way of accelerating wound healing and fighting off infections should any injury occur in the process. Inflammation-stimulating activities like vaccinations have been shown to evoke depression symptoms in rodents and a small sample of humans. Hence, continuous exposure to a stressful situation makes you more prone to suffering from depression.

Chronic stress –> Activated HPA axis –> Increased cortisol –> Inflammation –> Depression

3 Causes Of Depression You Probably Didn't Know

If and when prolonged stress causes depression depends on how stress interacts with a person’s genetic constitution.[ref]aan het Rot, Marije, Sanjay J. Mathew, and Dennis S. Charney. “Neurobiological mechanisms in major depressive disorder.” Canadian Medical Association Journal 180, no. 3 (2009): 305-313.[/ref] So, it will vary from person to person.

It is not a single stressful event but a buildup of such events that can cause depression.[ref]Causes of clinical depression. National Health Service.[/ref]

  • Traumatic life experiences: Loss of a loved one, pet, or finances; an accident, relocation, or rape; physical or mental abuse by parents, a spouse, siblings, or friends; failure at work or in relationships; social rejection; conflict with loved ones, friends, or colleagues can all cause depression.
  • Personality traits: Certain traits like low self-esteem, being overly self-critical, and the tendency to hide from others to deal with stress cause mental instability and increase the likelihood of depression.[ref]Causes of clinical depression. National Health Service.[/ref]
  • Giving birth: Some women struggle with the new responsibility of a baby. Hormonal imbalances paired with weight gain and other physical changes don’t make it any easier and may cause depression both during pregnancy and after childbirth.[ref]Causes of clinical depression. National Health Service.[/ref]
  • Substance abuse: While drugs like cannabis and heroin and alcohol can temporarily calm the mind and make you forget your worries, their long-term effects generally include depression.[ref]Causes of clinical depression. National Health Service.[/ref] Cannabis has been shown to cause depression in teenagers.
  • An offshoot of a chronic medical condition: The stress that comes with having to deal with a life-threatening condition (like cancer and coronary heart disease) or a life-long condition (like diabetes and Parkinson’s) may cause depression.[ref]Causes of clinical depression. National Health Service.[/ref] Depression may also occur in conjunction with other mental disorders like schizophrenia and bipolar disorder.
  • Changes in weather: Some people may struggle with adjusting to changes in weather (seasonal affective disorder), particularly the transition from autumn to winter. This may be a consequence of less available serotonin in brain synapses during winter months.[ref]Seasonal Affective Disorder. National Institute of Mental Health. National Institutes of Health.[/ref]

Now that you know the causes of depression, take the first step in removing the social stigma associated with this way-too-common mental illness. Here is how you can positively alter your mindset:

  • Don’t paint everyone with a broad brush: What may be a trigger for one may not be a trigger for another. Everyone’s genetics, personality, and life situations are different.
  • Consider a combination of triggers: A number of triggers together are likely to be responsible for depression. These triggers generally work over an extended period of time.
  • Keep an open mind: On one hand, you may struggle to pinpoint the cause of your depression, while on the other, you may falsely begin to think you’re depressed because you can identify with one too many points in this list. The key is in assessing your reactions to normal everyday situations.

You should be concerned if you experience no positive feeling whatsoever – not happiness, motivation, excitement, or love. Silver linings are there even if we don’t see them and even the worst of situations are redeemable. All we have to do is build enough courage to ask for help – help that is never too far.