Virtually all mental health researchers accept that Major Depression (MD) is a mental disorder, i.e., a brain dysfunction. I argue that this widespread belief should instead be treated as an untested hypothesis, and further, that this hypothesis is probably false. Instead, most MD in the general population is probably severe but normal sadness or grief. Here are seven reasons why:
1. Most Major Depression is caused by adversity
Ordinary sadness and grief are caused by adverse events. I suspect that a common view about MD is that it is fundamentally different, striking without cause, out of the blue. Most studies of MD do not even bother to measure recent negative life events. There is a consensus, however, that MD, too, is caused in large part by adverse events, and that events of higher severity increase the risk of MD. Many early studies found that about 80% of cases of MD had evidence of at least one adverse event (compared to a much lower rate among non-cases). See Figure 1.1.
More recent studies using twin designs have found similar results, and additionally, show the interaction between adversity and vulnerability factors such as female sex and neuroticism (see Figure 1.2).
The stressful life events in Kendler et al. (2004) included:
- assault (assault, rape, or mugging)
- divorce/separation (divorce, marital separation, broken engagement, or breakup of other romantic relationship),
- major financial problem
- serious housing problems
- serious illness or injury
- job loss (laid off from a job or fired)
- legal problems (trouble with police or other legal trouble)
- loss of confidant (separation from other loved one or close friend other than a spouse or partner)
- serious marital problems (involving a marital or marriage-like intimate, cohabiting relationship)
- serious difficulties at work
- serious trouble getting along with a close social partner
- serious personal crisis of a close social partner
- death or illness of a close social partner
Most of us hit by such adverse events would also experience low mood, sadness, loss of interest, insomnia, and other symptoms of MD. In fact, the study design of Kendler et al. (2004) instructed interviewers to rate the severity of the events as “what most people would be expected to feel about an event in a particular set of circumstances and biography….”
The causal effect of adversity on depression is most convincingly demonstrated by the finding that independent adverse events — those, like the death of a loved one, that could not be caused by the depressed individual — are powerful predictors of MD.
2. Diagnostic criteria for Major Depression were not developed to distinguish the ill from the healthy but instead to distinguish MD from other psychiatric disturbances
Almost all research on Major Depression (MD) diagnoses it using either the Diagnostic and Statistical Manual (DSM) criteria, or the very similar International Classification of Diseases (IDC) criteria. The current DSM-V criteria are basically the same as those in DSM-III, which initiated the modern era of depression research. These criteria are listed in the right-most column in Figure 2.1.
At some point in their lives, everyone will experience at least one of these symptoms, and most of us will probably experience most of them. Prima facie, none indicate brain dysfunction. To be diagnosed with MD under the DSM criteria, a person must be experiencing 5 or more symptoms most of the day for at least two weeks, and at least one symptom must be sad or depressed mood (dysphoric mood) or loss of interest or pleasure.
Where did these criteria come from? You might think they came from studies designed to distinguish mental illness from normal sadness and grief. If so, you would be wrong. Instead, they come from studies that were conducted among groups of individuals who had already been determined to suffer from a variety of severe psychiatric disturbances (or physical illnesses). The goal of these studies was to develop criteria that would enable different psychiatrists to reliably provide the same mentally ill patient with the same diagnosis, such as bipolar disorder or schizophrenia, not to distinguish the mentally ill from the healthy.
Specifically, the DSM-III criteria can be traced to Stone and Burris (1950), which was a clinical study of 50 selected cases; Cassidy et al. (1957), which was a quantitative study of one hundred manic-depressive patients compared to fifty medically sick controls; Feighner et al. (1972), which was a study of 314 psychiatric emergency room patients and 87 psychiatric inpatients. And Spitzer et al. (1975), which tested the reliability of the Research Diagnostic Criteria (RDC) with 218 psychiatric inpatients. See Figure 2.1.
None of the studies that defined MD as we understand it today included any healthy participants, nor any identified as experiencing only ordinary sorrow, sadness, or grief. Hence, there is no reason to believe that, when applied to the general population, the criteria developed in these studies would effectively distinguish the tiny minority of individuals with a genuine mental illness from the much larger number of individuals who were suffering ordinary low mood, sadness, or grief.
As Kenneth Kendler, one of the world’s preeminent depression researchers admits, “most of the diagnostic categories and the diagnostic criteria they contain have been accepted for historical rather than strictly empirical reasons” (Lux and Kendler 2010).
3. DSM criteria (mis)applied to community populations generated massive prevalence rates
It is no surprise, then, that when DSM criteria were first applied to the general population they generated implausibly high prevalence rates of mental illness. Over a quarter of the population (28.5%) was identified as suffering from a mental illness in the last year, and nearly half the population (48%) as having suffered a mental illness in their lifetimes. For MD, up to 10% were identified to have suffered an episode in the last year, and 17% to have suffered MD in their lifetime. See Figure 3.1.
Regier et al. 1998 acknowledged that these high prevalence rates called into question the validity of “diagnoses” based on DSM criteria in community populations:
Although it is possible that all of these community-based disorders are simply milder cases of essentially the same disorders seen in clinical settings, there are other possibilities as well. Based on the high prevalence rates identified in both the ECA and the NCS, it is reasonable to hypothesize that some syndromes in the community represent transient homeostatic responses to internal or external stimuli that do not represent true psychopathologic disorders. The human organism has a limited repertoire of response patterns to various physical, biological, and emotional stresses. Transient changes in blood pressure, pulse rate, body temperature, anxiety, or mood are not always indicators of pathology but of appropriate adaptive responses. It is possible that many people with currently defined mental syndromes (in particular among the affective and anxiety disorders) not brought to clinical attention may be having appropriate homeostatic responses that are neither pathologic nor in need of treatment — eg, other equivalents of grief reactions that meet clinical criteria but are not considered pathologic if they are time-limited.
Such eminently reasonable interpretations of MD in community populations have virtually disappeared from the scientific literature, and high prevalence rates are now reported without a bat of the eye. In the US, for example, the government reports that about 1 in 5 adolescent women (19.4%) suffered MD in the past year, i.e., putatively suffered a major disorder of the brain.
Regier, first author of the above quote, went on to co-chair the DSM-5 Task Force, which, ironically, was widely criticized for further medicalizing normal reactions to common life experiences. The most prominent critic was Regier’s predecessor, Allen Frances, chair of the DSV-IV Task Force. See, for instance, his book:
Robert Spitzer, chair of the DSM-III Task Force, expressed similar worries:
Regier and colleagues shot back that Frances’ and Spitzer’s criticisms were motivated by the loss of royalties from sales of DSM-IV products. Frances scoffed that these royalties were a relative pittance.
4. Depression is a continuum
If depression were a major brain disorder that could be identified by counting up symptoms that are common experiences, you might expect that folks with MD would stand apart from everyone else in the distribution of their symptoms. But they don’t. Although there is some debate, most studies have found that depression is dimensional, i.e., that it is “a quantitative elevation on a continuum of depression-relevant features found in all people” (Prisciandaro and Roberts 2005). As can be seen in Figure 4.1, there is no natural separation between those with lower depression scores and those with higher.
When Cassidy, developer of one of the historical antecedents to the DSM-III MD criteria (see Figure 2.1), was asked how he decided on the threshold, he replied, “It sounded about right” (Kendler et al., 2010).
There is no principled reason to conclude that higher scores indicate brain disorder instead of more severe sadness.
5. Major Depression usually remits in a few months
Many articles on MD emphasize that it is a chronic disease. This is not true for the majority of cases. The median duration of MD in a recent study of a nationally representative community sample was 6 months, and about 75% of cases remitted within a year. See Figure 5.1.
In addition, the majority of individuals who suffer MD will have a single episode in their lifetimes. A recent study based on a large, nationally representative sample found that, among individuals in remission from MD at baseline, the cumulative recurrence rate was 13.4% at 10 years, and 27.1% at 20 years (Ten Have 2018).
6. Onset of Major Depression is common at all adult ages
If MD were a genuine brain disorder, its epidemiology might resemble that of other genuine brain disorders, such as the epidemiology of developmental brain disorders, which occur early in life, or the epidemiology of brain disorders related to aging, i.e., those that occur late in life.
To compare MD with such brain disorders, I used the Institute for Health Metrics and Evaluation data visualization website to display results from the 2017 Global Burden of Disease Study. Here are the results for MD compared to four common developmental brain disorders (the x-axis on all plots is age, from 0-100 years, and the y-axis is either incidence – new cases – or prevalence, all on the same scale: 0 – 6%):
As you can see, new cases of MD are common starting in adolescence and throughout adulthood. In comparison, autism spectrum disorders and severe intellectual disability are relatively rare and present at birth (hence prevalence rather than incidence is reported). Bipolar disorder and schizophrenia are also relatively rare, with a sharp peak in incidence rates in late adolescence and early adulthood.
Similarly, although the incidence of MD increases with age, it does not resemble other brain disorders related to aging, such as dementia, Parkinson’s or stroke, which are exceedingly rare until after the age of 40 or 50:
7. Neurophysiological differences associated with MD do not necessarily indicate brain deficits
MD’s status as a “real” illness is often justified by pointing to biological differences associated with depression. The Mayo Clinic, for example, on its info page for MD, only lists biological factors as causes of MD, such as physical changes in the brain, brain chemistry, hormones, and genetics (adversity, in contrast, is a “risk factor”). Several biological differences associated with MD are depicted in Figure 7.1:
The brain, however, is a biochemical machine. It is not surprising that individuals in different emotional states, such as depressed vs. non-depressed, have differences in brain neurophysiology. All brain functions involve neurophysiological changes in the brain. Your brain is undergoing countless chemical changes as you read this post. If you remember anything you’ve read, for example, your brain has undergone some long-term chemical changes in synaptic connections between neurons. Differences in subjective experiences must be caused by physical differences in the brain. Indeed, if there weren’t biochemical and neurophysiological changes underlying MD this would be a shocking finding that would shake our materialist conception of the brain to its core.
Moreover, none of the studies I’ve seen of neurophysiological and biochemical differences in those with MD could distinguish differences from deficits, even in principle. Every study I’ve looked at has the following design: a group of participants that meet diagnostic criteria for MD is compared to a group of “healthy” controls, i.e., individuals without MD. But most of the individuals with MD are (1) experiencing sadness or low mood (one of two necessary symptoms), and (2) have suffered recent adversity. Most members of the control group, in contrast, are not experiencing sadness or low mood, and have not suffered recent adversity. Hence, MD is almost completely confounded with sadness and recent adversity.
All of the neurophysiological and other differences in Figure 7.1 that are identified as “impairments” or “pathophysiological features” are simply differences whose implications are currently unknown. They could easily be some of the biological bases of normal sadness and other functional responses to adversity.
MD is caused by adversity, such as loss of a loved one; it is characterized by symptoms such as sadness, low mood, and loss of interest, which most people experience when they experience adversity; it is diagnosed when the count of such common symptoms exceeds an arbitrary threshold; it is common among adolescents and adults of every age in the general population; it usually lasts for no more than a year; and most people will experience at most one episode in their lifetimes. Taken together, these facts provide considerable evidence for the hypothesis that most MD in the general population is simply severe sadness or grief.
I am far from the only one to make this argument. Horwitz and Wakefield wrote a book on it (note the Forward by Robert Spitzer, chair of the DSM-III effort):
If these arguments are correct, why do mental health researchers cling to the axiom that MD is a serious brain disorder, instead of treating this as a hypothesis? Here are a few possible reasons:
- Many psychiatrists form their initial intuitions about MD by working with inpatients. MD in these clinical populations can look quite different from MD in the general population. Because these individuals refer themselves or are referred by family members, for psychiatric treatment, their MD tends to be chronic, recurring, and have little connection to recent adverse events, making it seem much less like “normal” sadness or grief. Such rarer forms of MD are better candidates for a genuine disorder.
- $$$. The NIH budget for depression research is approaching half a billion dollars annually ($466 billion in 2018). Sales of antidepressants are generating revenues of around $11.6 billion annually. And Big Pharma kicks back a lot of bucks to “thought leaders” in medicine, including psychiatry. The flow of all these dollars depends on MD being a serious illness rather than ordinary sadness.
- Szasz was right: psychiatry aims to control undesirable behavior, and severe sadness and grief are aversive to sufferers and often inconvenient for social partners and employers.
- It’s politically incorrect to question the illness axiom, perhaps because it runs counter to the laudable effort to reduce the stigma of mental illness.
Regarding #4, viewing mental illness as an ‘illness like any other’ and promoting biogenetic causes have been thought to reduce stigma. Larkings and Brown (2018) conducted a systematic review of the impact of biogenetic beliefs regarding mental illness on stigma. They found, on the contrary, that among the public:
Overall, these reviews suggest that there are mixed ramifications associated with public endorsement of biogenetic causes. While biogenetic causes might help reduce blame, they might also contribute to negative consequences, such as increased perceived dangerousness, social distance, and pessimism around prognosis.
Among the mentally ill and mental health professionals, things were even worse:
The present review indicates that the endorsement of biogenetic causes does not reduce stigma in people with mental illness and in mental health professionals, and might actually increase stigma and negative attitudes towards mental illness.
Finally, even if most MD is normal sadness and grief sufferers will often still need help, sometimes from professionals. Much of my research and that of my grad students explores the possibility that some aspects of MD function to signal need to social partners. Treatment, though, would focus on solving real-life problems rather than altering brain chemistry.
If most MD, as it is currently diagnosed, is not a disorder, should we keep calling it Major Depression? Wakefield’s answer, and I think it’s a good one, is no. The term Major Depression should be reserved for genuine disorder, leaving many, if not most, cases of MD in the community as false positives (e.g., Wakefield and Schmitz 2013; Wakefield 2016). That is, the criteria in Figure 2.1 are insufficient to distinguish functional responses to adversity, such as sadness and grief, from disordered responses. Additional criteria that might reduce false positives include MD-levels of symptoms in the absence of adversity, that the severity of the response is disproportionate to the severity of the adverse event, the persistence of symptoms well past the adverse event (e.g., more than a year), or a high rate of recurrence.
So rename MD as “severe sadness”. What are the practical consequences? Treating “causes” of sadness rather than giving meds? But talk therapy has always been a legitimate part of treatment, nothing new here. People react to adversity in different ways, myriads of factors are in play, in similar circumstances some develop MD, others don’t. Even if MD develops “out of the blue”, it only means its causes, environmental or internal, are too difficult to identify. You can consider any condition as a symptom of something, as it develops in time.
Something about this topic seems like it cuts to the core of something more fundamental in our society. There are further implications to accepting this viewpoint that are outside of the MD debate. Food for thought..
Thank you for writing, Hagen.
I fully agree. Although there are several differentials not mentioned in the paper.
1 Because disease has always been related to medicine for treatment, the follow up perception a mental illness is a disease, would lead to the same recipe/ rather than assuming it would deliver a means to isolate patients from blame. Although it potentially results into the same ‘conclusion’/ solving problems does not emerge from neglecting them.
2 When experiencing circumstances leads to a different brain chemistry: then biology is an efect/ not a cause. Although the effect when severe could be irrereversible and be treated by chemistry only?
3 Limited time for psychiatrists in combination with the unknown of the ‘disease’ would lead to a quick fix, also because the environment likes that.
You would first need a better diagnose what exactly leads to these MD symptoms to construct a better treatment.
Adversity in general makes a lot of sense/ but at the same time worldviews from people differ as well as self imposed laws to be commited to: making a decisive difference.
4 It is very likely the position of young people within their family, between brothers and sisters (and parents) creates an underlying general source for types of worldview, not being investigated yet by science as far as I know.
5 I would not exclude parkinson and dementia fully ftom mental (adversity) disease.
Hi Edward, I would run with the same concept but throw the amygdala hierarchy centre (AHC) into the mix with the HPA. You see, as we all know, how you feel depends very much on your social relationships. ‘Confidence’ means ‘with your brothers’ i.e. socially secure. Anxiety is the fear that comes from being alone and unsupported. I postulated the existence of the AHC, in 2006, as it was necessary for my hypothesis about God. It had to be there, near or in the amygdala, so that ‘God’ could take the top slot and everyone, including Durkheim, could rub along together under His rule. Zinc et al, Noonan and others found the AHC experimentally two years later. If you peg yourself at the top of your own AHC then you believe that you are the supreme being and maybe you are a megalomaniac – or a doctor, as the joke goes. However, if your perception of your own standing is pushed down by adverse social interactions such as warfare, bullying / social exclusion / the experience of total failure then, from an evolutionary stance, you would do best to shut-down your systems to save your energy until the cavalry arrives – or run away or, maybe, turn to fight. But if things are that bad that you have to take on overwhelming odds then you had better ditch that ‘fear of death’ thing – really, go past caring if you die. Call that ‘suicidal depression’ if you will but, in extremis, in nature, it may be your best or only way ahead. Sadly, when men see their families removed from them, as in divorce battles, those switches appear to get flicked all too often with tragic results. Maybe that reaction needs to be recognised for what it is? Maybe we need to take care over those switches? Happiness is, apparently, not being more than two or three steps down from the supreme leader. This has been offered as the explanation for the emergence of social classes – it is better to be the top of a lower class than to be six or seven steps down in an overall class. Of course, the classes collapse into one when the wolf is at the door rather than when the gold is on the table. So, yes, don’t look at depression as anything but adaptive – nature doesn’t waste energy building in faults.
As egalitarian social animals, we feel best surrounded by equals who care about us. There’s an interesting new book on how inequality harms societies by Wilkinson and Pickett called The Inner Level. They share data showing that inequality actually drives humans into narcissistic or anxious/depressed mental states, childish states I would say. We are made to be born into cultures that care about us and we usually develop through narcissistic and anxious/depressed states at a fairly young age as we grow into a more adult development of compassion and confidence. Sharing honor- the most precious social food- makes everyone happy. But what do you do in cultures of fake hierarchy and status? In such societies, when would individuals see the opportunity or potential to really value themselves and others? Without this, how much extra stress do people feel in these societies, not feeling supported, belonging, feeling they must worry about increasing their material worth or losing it. When you grow up hearing some of your own people can be more worthy than others, and that some can be less worthy living on the street , I think our maturation gets stunted in many ways. But with the right symbotypes and compassionate, empathic habits of concentration humans can get back on track to more pro-social fulfillment. I’d like to see studies on how depression might be a response to hierarchical cult-ures that forgot how to encourage adult development.
Not sure whether you’re writing on the over-diagnosis of major depression? Reasons #2 and #3 don’t even address the question.
Reason #1 has conceptual problems, starting with making sure you avoid a propter hoc, ergo hoc fallacy. In the evidence offered, the notion “neuroticism” has nothing to do with brains needs a little explanation. In particular, the expression of sadness is socially permissible when there’s a conventionally acceptable reason. How does this affect diagnosis before and after events? Is a divorce the cause of depression or is it the effect of depression? If it’s all about adversities, shouldn’t the intensity of the adversity correlate with the intensity of the non-pathological sadness? That correlation is what needs to be demonstrated, isn’t it? Otherwise, isn’t this close to saying they just need to give it time and get over themselves? Lastly, how does all of this correlate with suicide?
Reason #4 somehow assumes that Major Depression must present like an infectious disease or trauma. It is not clear to me that there aren’t straightforwardly physiological diseases that present a continuum in severity of symptoms. Your argument would explain away black lung for instance, so far as I can tell.
Reason #5 is pertinent. My suggestion is that Major Depression is when it doesn’t go away in a year. Incidentally, the rate of return after “remission” is as much of interest in depression as it is in cancer. This is a powerful reason for arguing MD is over-diagnoses, as were #2 and #3. But that’s not what the title of this article seems to be about, hence the confusion on my part.
Reason #6 assumes that Major Depression must be unrelated to length of exposure to adverse environmental conditions. But this is only relevant if you insist that Major Depression must be wholly endogenous. I’m not sure that’s even the case for schizophrenia. Cancer rates tend to go up with age as well, with very specific exceptions. Is Major Depression a disorder that renders the person less resilient to the common trials of life?
Reason #7 has the usual difficulties with understanding neuroscience compounded with the problem that mood is not a simple brain function and is intrinsically difficult to measure. Impaired cognitive integration so that someone is, for example, hearing some thoughts as exterior voices, is pretty straightforward by contrast.
Your suggestion in the conclusion that recurrent MD is the candidate for a true disorder should I think have been at the forefront, not jumbled with, well, dubious conspiracy theories ($, gaslighting, political correctness.)
[…] which reads in part “the medical community has largely refuted this theory” or Seven Reasons Why Most Major Depression is probably not a brain disorder on The Evolution Institute). The truth is we are much more complicated beings that just bone, […]
Criticizing a problem without providing solutions and the consequences of said solution(s) is largely useless. E.g. Your article is useless.
I have personally spoken to many people who have suffered from debilitating depression for years, or nearly their entire life. It’s not hard to find these people if you just look.
I also wouldn’t be surprised if some subset of people who only experience one major depressive episode or
Furthermore, a vast majority of societies do not foster a culture that is beneficial to resolution of depression. We are taught to hide our feelings and suppress these things as unnatural. I believe this also leads to what should have been a normal, temporary “grief” or stress caused depression, turning into a long-term disorder that has likely permanently affected how our brain works.
I can concur that the majority of depressed people do not have a genuine, life-long disorder. Experiencing one episode of a major depressive disorder is thought to have about a 20% recurrence rate. I’m sure this is a bit higher than the actual number, but we can take that 20% to be the approximate amount of people with a true neurophysiological dysfunction — FAR from rare.
You obviously enjoy dismissing claims of neurochemical changes and the likes, as even reading and storing information does so. This is by far a false analogy, pretending in your delusion that every change is equivalent and produces the same effects.
We also do not understand how our hrains even function entirely, or how all of these processes interconnect. Even more confoundingly, at a quantum mechanical level, it is likely that an effect may PRECEDE its cause when particles have an observer. So, to write such dismissive critiques without offer constructive criticism, is absolutely repugnant.
Nice review, Ed. I certainly agree that most depression arises from life situations, not brain abnormalities. Your nicely organized summary of the evidence confirms that. And I fear the current Covid calamity will cause situations that arouse desperate depression in millions.
After seeing thousands of patients in a clinic, however, it is clear that many of them have depression symptoms that are not connected to life events or situations. They, and often their parents and sibs and children, experience excess low mood in response to ordinary events and extreme episodes of depression for no reason. Every patient needs individual evaluation and the same individual can have two episodes of depression with two different causes.
The chapter on low mood in my book on evolutionary psychiatry is called “Low Mood and the Art of Giving Up” It emphasises the adaptive value of low mood in certain situations.
The next chapter, “When the Moodostat Fails” is about why the mood regulation system is vulnerable to failure.
I think both perspectives are important for understanding depression in evolutionary context.
Your Canadian Journal of Psychiatry article from a few years ago provides a good summary and I recommend that article to people for a good overview.
My current ideas about all of this are in my new book “Good Reasons for Bad Feelings; Insights from the Frontier of Evolutionary Psychiatry.” David twice told me he would feature the book on this website, but he still has not done so and even a third nudge has not helped. Several people have told me my book is too gentle about group selection, but naive views about group selection and failure to recognize the power of social selection are severe obstacles to a sophisticated application of evolutionary biology in psychiatry. I wish David and this website would do a full court press to correct the common misconception that alleles that become less common with every generation within a group can nonetheless become more common because of their benefits to the group. This could be done even while we all continue the discussion about the subtleties of how natural selection shapes prosocial traits and their associated mental health problems. Full info about the book is at http://goodreasons.info
This is such an interesting topic and quite a debate. I happen to sit in the most unique situation though and have quite a wide view with MD. As a licensed therapist, I see plenty of people experiencing depression due to a catastrophic events. Many of those people can overcome a depression in time with good techniques. Obviously, some are deep rooted in events from the past that need more work, but many people can overcome in less than a year. On the other end, my sister actually experiences chemical imbalanced MD and needs medication to balance her out. It runs in the family with several people in the gene pool also experiencing depression and my sister started feeling these unusual “down moods” when she was 13. And she hadn’t had any serious trauma in her life yet so it clearly wasn’t linked to anything in the environment. I think there’s still a ton of research to do on all different forms of MD, but we are definitely further along with our work than 20 years ago. So imagine where we could be in 20 more.