The Chemical Imbalance Theory of Depression: still promoted but still unfounded

A long overdue debate is raging about the chemical imbalance theory of depression. Having been deluged with this idea for two decades now, the general public has come to believe that it is a scientifically proven fact. An LBC radio presenter recently announced that he had suffered from depression and he knew it was a chemical imbalance. ‘All the goodness is flushed out of the brain [and you have to] top it up now and again; that’s why you need medicine,’ is how he expressed it.

Pharmaceutical industry propaganda has led the way in advocating this view, but the medical profession continues to endorse it too. On 18th March 2014, viewers of This Morning, a national UK television programme were advised by the programme’s resident General Practitioner, Dr Chris Steele, that depression consists of a chemical imbalance in the brain caused by depletion of serotonin (1).

Neither is it simply a few rogue individuals who are promoting this line, as claimed by leading US psychiatrist Ronald Pies in a recent article (2). The American Psychiatric Association’s public information on depression, entitled Lets Talk Facts about Depression, claims that ‘abnormalities in two chemicals in the brain, serotonin and norepinephrine, might contribute to symptoms of depression’ and later on that ‘antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain’ (3).

The UK’s Royal College of Psychiatrists public information leaflet on antidepressants states: ‘we don’t know for certain, but we think that antidepressants work by increasing the activity of certain chemicals in our brains called neurotransmitters. They pass signals from one brain cell to another. The chemicals most involved in depression are thought to be serotonin and noradrenalin’ (4).

As Pies demonstrates, however, leading psychiatrists have been trying to distance themselves from the chemical imbalance theory of depression in the last few years, because the evidence to support it has simply never been there.

So what is the evidence? Two brain chemicals have been suggested to be involved in depression- noradrenaline (norepinephinre) and serotonin. The evidence on noradrenalin has long been acknowledged to be contradictory, as described in the principle American textbook of psychiatry in 2001, with studies showing increased, decreased and equal levels of activity in depressed patients compared to controls (5).

Evidence on serotonin comes principally from studies of serotonin receptors and ‘serotonin depletion’ studies. Results of studies of the serotonin 1A receptors in living subjects are contradictory, with some finding lowered levels of receptors in people with depression compared to those without (6,7), some finding no difference (8,9) and some finding raised levels (9,10)! Post mortem studies of receptors in the brains of people who have died by suicide are similarly inconsistent (11,12,13).

There are two types of ‘serotonin depletion’ study. One involves giving people a diet low in tryptophan, the amino acid that the body uses to manufacture serotonin. Some of these studies show a lowering of mood in people who have previously had depression and been treated with SSRIs. The effect does not occur in volunteers (14), however, suggesting that, if anything, it is a consequence of previous drug treatment. The second type of study involves a powerful serotonin depleting chemical called parachlorophenylalanine, which was used in animal and human experiments in the 1960s and 70s. This produced a state of insomnia, aggression, hypersexual behaviour, irritability, hypersensitivity to the environment, agitation and paranoia, but nothing resembling depression (Mendels and Frazer 1974).

Pies claims that psychiatric theories of depression are more sophisticated and incorporate social and psychological influences. But for all his talk about the ‘biopsychosocial’ model, Pies, along with most of the psychiatric establishment, cannot relinquish the disease model of depression – the idea that depression consists of the manifestations of a discrete biological mechanism (or mechanisms) like a bodily disease.

Of course, there are brain events and biochemical reactions occurring when someone feels depressed, as there are all the time, but no research has ever established that a particular brain state causes, or even correlates with, depression. Alongside biochemical theories numerous findings have been trumpeted as indicating the disease-basis of depression, including variations in cortisol (stress hormone), brain volume abnormalities and neurotrophic factor. In all cases studies yield inconsistent results, and none have been shown to be specific to depression, let alone causal (17).

The fact that more than 50 years of intense research efforts have failed to identify depression in the brain may indicate that we simply lack the right technology, or it may suggest we have been barking up the wrong tree!

Social constructivist thinkers have highlighted that emotions are not equivalent to physical states or sensations like being hungry, tired or having a cold (18). They are not simply involuntary experiences thrust upon us by our biology. They are sophisticated and specifically human responses to the world around us that involve complex moral evaluations of events.

This is not to deny that some individuals suffer more than others, and that some need assistance to climb out of the dark place they have become stuck in. The disease-model, however, is ultimately not helpful, as well as being unfounded. For all its attempts to incorporate social factors, the disease-model renders depression meaningless, because biology effectively trumps other influences. It conveys the message that we are powerless to change ourselves or our situations. When things go wrong, it persuades us we need a pill to put them right. This approach may appeal to some people, and I am in no way disparaging those who chose to follow it. But it is important that everyone knows how little evidence there is to support it.

References:

1)      https://www.madinamerica.com/2014/04/open-letter-re-morning-feature-depression/.

2)      http://www.mentalhealthexcellence.org/nuances-narratives-chemical-imbalance-debate-psychiatry/

3)      http://www.psychiatry.org/mental-health/lets-talk-facts-brochures

4)      http://www.rcpsych.ac.uk/healthadvice/treatmentswellbeing/antidepressants.aspx

5)      Dubovsky SL, Davies R, Dubovsky AN. Mood Disorders. In: Hales RE, Yudofsky SC, editors. Textbook of Clinical Psychiatry.Washington: American Psychiatric Association; 2001.

6)      Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, et al. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999 Nov 15;46(10):1375-87.

7)      Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, et al. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000 Feb;57(2):174-80.

8)      Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, et al. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 2004 Dec;61(12):1271-9.

9)      Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, Huang YY, et al. Altered Serotonin 1A Binding in Major Depression: A [carbonyl-C-11]WAY100635 Positron Emission Tomography Study. Biol Psychiatry 2006 Jan 15;59(2):106-13.

10)  Reivich M, Amsterdam JD, Brunswick DJ, Shiue CY. PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression. J Affect Disord 2004 Oct 15;82(2):321-7.

11)  Lowther S, De Paermentier F, Cheetham SC, Crompton MR, Katona CL, Horton RW. 5-HT1A receptor binding sites in post-mortem brain samples from depressed suicides and controls. J Affect Disord 1997 Feb;42(2-3):199-207.

12)  Matsubara S, Arora RC, Meltzer HY. Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims. J Neural Transm Gen Sect 1991;85(3):181-94.

13)  Stockmeier CA, Dilley GE, Shapiro LA, Overholser JC, Thompson PA, Meltzer HY. Serotonin receptors in suicide victims with major depression. Neuropsychopharmacology 1997 Feb;16(2):162-73.

14)  Murphy FC, Smith KA, Cowen PJ, Robbins TW, Sahakian BJ. The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology (Berl) 2002 Aug;163(1):42-53

15)  Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, Moreno FA, et al. Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry 1999 Jul 15;46(2):212-20.

16)  Mendels J, Frazer A. Brain biogenic amine depletion and mood. Arch Gen Psychiatry 1974 Apr;30(4):447-51.

17)  Moncrieff J, Rebuttal: depression is not a brain disease. Can J Psychiatry 2007;52: 100-101

18)  Harré, R. An outline of the social constructionist viewpoint. In The Social Construction of Emotions, Ed R. Harré, Basil Blackwell: Oxford, 1986, 2-14

52 thoughts on “The Chemical Imbalance Theory of Depression: still promoted but still unfounded

  1. Pingback: Post Of The Week – Thursday 1st May 2014 | DHSG Psychology Research Digest

  2. Pingback: The Chemical Imbalance Theory of Depression: Joanna Moncrieff | Palace Gate Counselling Service

  3. Pingback: La teoria dello squilibrio chimico : SFOGLIA CITTÀ

  4. Pingback: Chemical imbalance myth takes a big public fall (no, antidepressants do NOT correct an imbalance of serotonin, nor do other psychiatric drugs correct anything at all) – Beyond Meds

  5. If you want to know about two women that have recovered from schizophrenia see this documentary. A message of hope two all these people that are suffering because of mental illness and psychiatric drugs. Recovering is possible. We don’t want more lies from industry!

  6. Disease model contributes to learned helplessness? Very plausibly if it is constructed that escape depends to biological change showing up out of nowhere. Indeed, rumination on this ‘fact’ could lead to cascades of thought: ‘my biology is a curse,’ ‘my genes are to blame.’ That would be wrong, but you would have to have considerable prescence of thought not to be seduced by these apparent truths.
    I think the chemical imbalance theory sometimes functioned to prevent conflict between doctor and patient. Jolting someone out of ingrained behaviours can be done by violent confrontation (not literally!) But this might create cause for complaint!

    Very interesting blog.

  7. I do believe that at least in my case that my mental disorder symptoms were caused by some kind of imbalance in biochemistry, Since the age of 13, I have had severe depression, irritability, mood swings, extremely erratic sleep patterns, and later on in life, mania and psychosis(due in part to MDMA and amphetamine). For years, I was treated unsuccessfully with antipsychotics and anti-depressants which had extremely unpleasant and potentially damaging side effects.

    I noticed that when I had an episode of mania/psychosis that my recovery took the same amount of time without drugs as it did with them, indicating that at best the antipsychotics were acting as some kind of placebo with mind-numbing effects and associated Parkinsons symptoms. The antidepressants did actually have a positive effect on mood, but they made me feel euphoric and agitated, as well as nauseous and had a constant headache- they did not make me feel normal. I was very aware I was taking a drug, but it was so unpleasant I stopped taking them and thought that I would be stuck with depression forever.

    I have a Biology degree and have been seeking answers to why I had mental health problems for years with little success because I was asking the wrong questions, although I was on the right track. My symptoms showed a clear seasonal pattern, with severe depression in the winter, mood swings in the spring, euphoria in summer and further mood swings in autumn and that my moods tracked the weather very reliably, but my mood was volatile all year round in response to stress. Recently, I stumbled upon some research into how bipolar disorder and other affective disorders seems to be related to disruption of circadian rhythms and also that there seemed to be epigenetic factors involved. I found out that magnesium and zinc were involved in regulation of circadian rhythms and also DNA methylation.

    I decided to do an experiment and bought some combined magnesium and zinc tablets. I was not at all confident that it would do anything, but on the day I started taking them, my symptoms disappeared. My mood swings and irritability disappeared, my depression gone. My body clock is now stable and I wake up in the morning and feel tired at night. I have no side effects, or feel like I’m on drugs.So it seems that my mental disorder may be caused by a nutritional deficiency, yet not one medical professional even considered my diet, and were all too willing to prescribe me largely useless drugs. I am both relieved I seem to have found an answer to my suffering and at the same time angry with the medical profession for failing to spot something that could have been solved so easily with some simple minerals.

    I am also happy that an Australian research team has recently started a clinical trial with nutrient therapy.

    http://www.abc.net.au/am/content/2014/s4083682.htm

    • We are all individual at a biological level, and no doubt some people have a greater propensity than others to emotional difficulties of various sorts. There is no evidence that there is a specific chemical imbalance at the root of this, however, at least not one that can be isolated from all the other things going on both at a biological and social level. Like many other people, you found the drugs that were meant to target this mythical imbalance did you no good at all- quite the opposite. I am very happy you found a solution, and I hope it continues to work for you. Although I am certain a good and balanced diet is important for our overall wellbeing, somehow I can’t believe it can be quite so simple.

      • I agree it probably isn’t as simple as I’m making out and that what works for me may not work for other people. The body and brain are complex systems and I think the single neurotransmitter theory of depression is overly simplistic. From what I can tell, magnesium and zinc act as co-factors for a lot of very important enzymes, so my improvement may be due to a range of systemic effects. I think doctors and pychiatrists should at least consider whether nutrients could be beneficial before prescribing drugs since a healthy diet is important for general physical health as well as mental health.

  8. Reblogged this on Pluan and commented:
    “Of course, there are brain events and biochemical reactions occurring when someone feels depressed, as there are all the time, but no research has ever established that a particular brain state causes, or even correlates with, depression.”

  9. Pingback: Busting the Chemical Imbalance Myth by MONICA CASSANI | AETHERFORCE

  10. Pingback: Depression: It’s Not Your Serotonin | Mad In America

  11. Pingback: Depression: It’s Not Your Serotonin - Waking Times : Waking Times

  12. Pingback: Depression: It’s NOT Your Serotonin - The Tom Hitchens Community

  13. Pingback: Depression: It’s Not Your Serotonin | WebInvestigatorKK

  14. Pingback: Depression Is Not Your Serotonin | The Telemedicine Reporter

  15. Pingback: Depression: It’s Not Your Serotonin - Kelly Brogan MD -

  16. does anyone know, is it possible to get a real brain damage caused by taking ssri for longer time? im 30 years old and took them since i’ve been 18 years old, not the whole time but many years and by the moment i’m sure it won’t ever be possible for me to live without them again. after a few weeks without medication i feel really sick, but not depressed, just sick and have to take them again. is it maybe exactly what pharma industrie wants from us, to be dependet on those ssri forever?

  17. Pingback: Antidepressants, Serotonin and the Pursuit of Happiness | Hearthside Healing

  18. Pingback: What The Pharmaceutical Industry & Your Doctor Don’t Tell You About Depression |

  19. Pingback: Lo que la industria farmaceútica y tu doctor no te dicen sobre la depresión | Periodismo Alternativo

  20. Pingback: Lo que la industria farmaceútica y tu doctor no te dicen sobre la depresión | El Bien Público

  21. Pingback: What The Pharmaceutical Industry & Your Doctor Don’t Tell You About Depression : Waking Times

  22. Pingback: What The Pharmaceutical Industry & Your Doctor Don’t Tell You About Depression | Alternative News Network

  23. Pingback: Antidepressants Double Risk Of Suicide And Aggression In Young People, Study Finds | Fox7News.Net

  24. Pingback: Antidepressants Double Risk Of Suicide And Aggression In Young People, Study Finds - Atheist Boutique

  25. Pingback: How Depression Affects Brain Structure & What You Can Do To Change It Back | Collective-Evolution

  26. Pingback: How Depression Affects Brain Structure & What You Can Do To Change It Back – HEALTH.INFO

  27. Pingback: How Depression Affects Brain Structure & What You Can Do To Change It Back - New Earth Media

  28. Pingback: HealthFreedoms – How Depression Affects Brain Structure & What You Can Do To Change It Back

  29. Pingback: 9 Depression Facts and the Indicative Statistics

  30. Pingback: Character is the Capacity for Happiness: An Example | Domestic Policy

  31. Pingback: Study Outlines Why Antidepressant Drugs Could Be Completely Useless & Harmful | Collective-Evolution

  32. Pingback: Study Outlines Why Antidepressant Drugs Could Be Completely Useless & Harmful - WAKING SCIENCE

  33. Pingback: Study Outlines Why Antidepressant Drugs Could Be Completely Useless & Harmful - New Earth Media

  34. Pingback: The Serotonin Myth Explained - The Alternative Daily

  35. Pingback: What Big Pharma Doesn’t Want You To Know About Dopamine & Serotonin Imbalances Within The Brain | Collective-Evolution

  36. Pingback: What Big Pharma Doesn’t Want You To Know About Dopamine & Serotonin Imbalances Within The Brain - New Earth Media

  37. Pingback: Subliminal Sensibility

  38. Pingback: What Big Pharma Doesn’t Want You To Know About Dopamine & Serotonin Imbalances Within The Brain – Subliminal Sensibility

  39. Pingback: What Big Pharma Keeps Hidden About Depression - The Tom Hitchens Community

  40. Pingback: WHAT BIG PHARMA DOESN’T WANT YOU TO KNOW ABOUT DOPAMINE & SEROTONIN IMBALANCES WITHIN THE BRAIN |

  41. Pingback: How depression affects brain structure & what you can do to change it back - BBN Community

  42. Pingback: How Depression Changes Your Brain (And Ways to Reverse It)

  43. Pingback: How Depression Changes Your Brain (And Ways to Reverse It) | Make Me Fool

  44. Pingback: How Depression Changes Your Brain (And Ways to Reverse It) | Healthiest One

  45. Pingback: How Depression Changes Your Brain (And Ways to Reverse It) – us health guardian

  46. Pingback: What Big Pharma Doesn’t Want You To Know About Dopamine & Serotonin Imbalances Within The Brain – SubSense

  47. Depression and many other mental problems are caused by the electrical malfunctioning of the autonomic nervous system and the enteric or intrinsic nervous system. Having depression means there is not enough electricity in the parasympathetic nervous system, a part or component of the autonomic nervous system within the central nervous system. When you have anxiety there is too much electricity in the sympathetic nervous system, another or the other part or component of the autonomic nervous system. Chemical imbalances in the brain and body do not cause mental and emotional problems. The bioelectric rules the biochemical. The body and brain are highly electrical. The enteric or intrinsic nervous system is in the gut located in the colon or large intestine. The gut is sometimes called “the second brain”. I’m sure all mental and emotional problems are the results of faulty and abnormal electrical current or activity in the nervous systems in the body.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s