{"id":3292,"date":"2023-07-17T14:43:15","date_gmt":"2023-07-17T14:43:15","guid":{"rendered":"https:\/\/desmolysium.com\/?p=3292"},"modified":"2024-10-03T12:34:52","modified_gmt":"2024-10-03T12:34:52","slug":"depression","status":"publish","type":"post","link":"https:\/\/desmolysium.com\/depression\/","title":{"rendered":"Depression \u2013 Basic Principles"},"content":{"rendered":"\n
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Depression is the leading cause of disability worldwide. People who have never been depressed can hardly imagine what it means to always \u201cfeel like shit\u201d and to live with a constant background of depression.<\/p>\n\n\n\n

Major depression is not just some made-up term for people having a bad day \u2013 it is a serious mental state, characterized by a severe imbalance in neurotransmitters and neuroplastic processes, which makes the individual emotionally unstable, unable to focus or to think clearly, kills joy, and removes interests (sometimes including one\u2019s own survival).<\/p>\n\n\n\n

Even though not a helpful explanation, it is generally thought that \u201cdepression is brought about by a combination of biological, psychological, and environmental factors\u201d. It seems that every depressed person has his\/her own somewhat unique mix & match variation of causes as well as symptoms.<\/p>\n\n\n\n

Sometimes, depression is caused by endogenous changes that seem to happen for no reason, other times, depression is caused by external life events, and most of the time it is a combination of the two.<\/p>\n\n\n\n

In this article, I discuss the basic principles behind depression, its cause, and its treatment. The practical aspects are discussed here: What Kind of Antidepressant Should I Choose?<\/a><\/p>\n\n\n\n

Table of Contents<\/div><\/div>
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    Different forms of depression<\/h2>\n\n\n\n

    There are various forms of depression. The most common are anxious depression (also called melancholic depression) and endogenous depression (also called atypical depression). Though in reality, there probably are many more different spectra, and combinations thereof, of depression.<\/p>\n\n\n\n

    Depression is defined by a deviation from baseline<\/em>. For example, if a generally happy and cheerful person experiences depression, their happiness and cheerfulness (their \u201cbaseline\u201d state) is depressed \u2013 which literally means \u201cpressed down\u201d.<\/p>\n\n\n\n

    Unfortunately, true biological depression, such as the two forms of depression discussed shortly, is usually lumped together with many other states of \u201cprolonged subjective suffering\u201d, which may or may not be rightfully called depression from a biological perspective.<\/p>\n\n\n\n

    Melancholic depression<\/strong><\/h4>\n\n\n\n

    Melancholic depression is characterized by low mood, hopelessness, and anxiety about the future. This is the form of depression that most people think of when they think of depression.<\/p>\n\n\n\n

    Melancholically depressed individuals cease to experience pleasure or joy from things they normally would enjoy (\u201canhedonia\u201d<\/a><\/strong>). While some patients are sad and anxious, others say they are feeling absolutely nothing inside, positive or negative. HPA-axis activity and cortisol levels are generally high in this form of depression. A major risk factor for this kind of depression is a shitty subjective effort-reward imbalance (“I am working hard but nothing comes of it.”) and large amounts of stress.<\/p>\n\n\n\n

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    Atypical depression<\/strong><\/h4>\n\n\n\n

    Atypical depression is characterized mostly by very low energy levels (instead of a very low mood). The person needs to sleep a lot (hypersomnia), gains weight, and simply moving around is often perceived to be an onerous task (\u201cleaden paralysis\u201d). HPA-axis activity and cortisol levels are typically low in this form of depression.<\/p>\n\n\n\n

    This form of depression is less common than melancholic depression and is thought to have a stronger genetic underpinning. \u201cAtypical\u201d depression is somewhat of a misnomer that implies that this kind of depression is \u201cweird\u201d or rare \u2013 it is neither. This form of depression responds well to MAO inhibitors<\/a><\/strong>.<\/p>\n\n\n\n

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    Evolutionary theories of depression<\/h2>\n\n\n\n

    Does (biological) depression serve an evolutionarily adaptive function or is it a true dysfunction? There are arguments to be found for both sides.<\/p>\n\n\n\n

    Some researchers argue that the capacity for depressive behavior, even though personally unpleasant, was adaptive in our ancestral environment. Many theories have been put forth, of which I will now briefly introduce three. These theories are not mutually exclusive.<\/p>\n\n\n\n

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    \u201cStress hypothesis\u201d<\/strong><\/h4>\n\n\n\n

    Some researchers believe that biological depression may have evolved as a protective mechanism to prevent people from running themselves into the ground. According to this theory, prolonged stress triggers biological depression (a downward deviation from baseline) to \u201chelp\u201d individuals let go of unattainable goals and\/or withdraw from desperate situations.<\/p>\n\n\n\n

    If an individual’s energy and mood deteriorates she is more likely to let go and withdraw. Conversely, if an individual’s energy and mood did not deteriorate, she might continue to overexert herself and die. Indeed, prolonged stress (i.e., perceived effort) seems to be one of the greatest risk factors for developing depression.<\/p>\n\n\n\n

    \u201cInflammation hypothesis\u201d<\/strong><\/h4>\n\n\n\n

    Certain subtypes of depression are due to sickness behavior. \u201cSickness behavior\u201d refers to a set of behavioral and mental changes that occur in response to an infection or inflammation.<\/p>\n\n\n\n

    Sickness behavior is characterized by a range of symptoms, including brain fog, fatigue, lethargy, lowered mood and self-confidence, anhedonia<\/a><\/strong>, a desire to withdraw, and altered sleep and appetite. These changes are thought to be an evolutionary adaptation that enables the body to conserve energy and focus on fighting infection or inflammation. Furthermore, it is thought that “sickness behavior” also induces a withdrawal from group living, which would help the group as well as prevent ostracization of the individual.<\/p>\n\n\n\n

    Indeed, many of the genes associated with depression are involved in inflammation and immune regulation. I discuss this in more detail here (Ibuprofen<\/a><\/strong>) and here (Low-dose Naltrexone<\/a><\/strong>).<\/p>\n\n\n\n

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    \u201cRank-theory hypothesis\u201d<\/strong><\/h4>\n\n\n\n

    Some researchers speculate that depression may have proved useful in dominance conflicts that are unlikely to be won. According to the \u201crank theory of depression\u201d,  sustained melancholy, withdrawal behavior, and a fixation on personal shortcomings and insufficiencies may ensure that the weak “keep their heads down” and don’t overreach themselves, which may prove evolutionarily fatal.<\/p>\n\n\n\n

    The rise of depression and anxiety in young people coincides with the advent of social media, and there is probably a causal connection at play. Social media constantly floods people with \u201cevidence\u201d that many others have it better. I like what Naval Ravikant has to say about it: \u201cSocial media make celebrities of all of us. And celebrities are the most miserable people on Earth.\u201d<\/p>\n\n\n\n

    According to this theory, depression may represent a fitness-enhancing adaptation to group living. Indeed, if individuals are \u201closing\u201d in life, they are more likely to develop depression. In support of this may also be the fact that adolescents are often depressed (because most adolescents are not on top of the hierarchy – aka the cool kids). Further support for this theory is evidence that antidepressants may overturn dominance hierarchies in relationships.<\/p>\n\n\n\n

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    Whether depression is a final common pathway of all of the above, or whether all of the above only superficially and phenotypically resemble each other, is currently not known, in part because it is hard to test.<\/p>\n\n\n\n

    Differentiating depression and \u201csuffering\u201d<\/h2>\n\n\n\n

    Regardless of evolutionary theories, it is important to differentiate between biological depression and \u201csuffering\u201d.<\/p>\n\n\n\n

    A psychiatrist once complained to me that what patients mean by \u201cdepression\u201d does not always correspond to what doctors mean by \u201cdepression\u201d. Most lay people consider depression to be a non-specific state of long-standing unhappiness, gloominess, low self-esteem, little joy, and just overall not being satisfied with their lives.<\/p>\n\n\n\n

    This is quite different from what the medical system means by \u201cdepression\u201d, namely different forms of depression as distinct downward deviations from someone’s baseline<\/em> state such as it is seen in melancholic depression, atypical depression, or bipolar depression.<\/p>\n\n\n\n

    Unfortunately, the term \u201cdepression\u201d has taken on multiple meanings, and \u201cdepression\u201d is used interchangeably to describe many different etiologically and phenotypically distinct states, which often results in confusion.<\/p>\n\n\n\n

    Given that we do not have useful biomarkers for depression, it is hard to tell whether someone is truly depressed (i.e., biological depression as a neuropathological process) or just \u201csuffering\u201d.<\/p>\n\n\n\n

    Nowadays, a lot of people claim that they are \u201cdepressed\u201d and there are a lot of reasons why that might be the case, whether truly (biologically) depressed or not.<\/p>\n\n\n\n