Chemical imbalance

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Chemical imbalances is one hypothesis about the cause of mental illness. Other causes that are debated include psychological and social causes.

The theory argues that neurotransmitter imbalances within the brain are the main causes of psychiatric conditions and that these conditions can be improved with medication which corrects these imbalances. The phrase originated from the scientific study of brain chemistry. In the 1950s the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were accidentally discovered to be effective in the treatment of clinical depression.[1]

These findings and other supporting evidence led scientist Joseph J. Schildkraut (1934–2006) to publish his paper called "The Catecholamine Hypothesis of Affective Disorders" in 1965.[2][3][4] Schildkraut associated low levels of neurotransmitters with depression.

Research into other mental illnesses such as schizophrenia also found that too much activity of certain neurotransmitters such as dopamine was correlated to these disorders. In the scientific community this hypothesis has been referred to as the "Monoamine hypothesis". This hypothesis has been a major focus of research in the fields pathophysiology and pharmacotherapy for over 25 years.[5]

This conceptual framework has been challenged within the scientific community, though no other demonstrably superior hypothesis has emerged. While the hypothesis has been shown to be simplistic and lacking, there is sufficient evidence to consider it as a useful heuristic in the aiding of our understanding of brain chemistry and explaining pharmacotherapy.[2][5]

Wayne Goodman, Chair of the US Food and Drug Administration Psychopharmacological Advisory Committee, has described the serotonergic theory of depression as a "useful metaphor" for understanding depression, though not one that he uses with his own psychiatric patients.[6] In 2008, psychiatrist Peter Kramer stated that the serotonin theory of depression had been declared dead prematurely.[7]

Monoamine hypothesis[edit]

The monoamine hypothesis is a biological hypothesis stating that depression is caused by the underactivity in the brain of monoamines, such as dopamine, serotonin, and norepinephrine.

In the 1950s the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were accidentally discovered to be effective in the treatment of depression. These findings and other supporting evidence led Joseph Schildkraut to publish his paper called "The Catecholamine Hypothesis of Affective Disorders" in 1965.[3] Schildkraut associated low levels of neurotransmitters with depression. Research into other mental impairments such as schizophrenia also found that too little activity of certain neurotransmitters were connected to these disorders.

Dopamine hypothesis[edit]

In studying the causes of schizophrenia, particular focus has been placed upon the function of dopamine in the mesolimbic pathway of the brain. This focus largely resulted from the accidental finding that a drug group which blocks dopamine function, known as the phenothiazines, could reduce psychotic symptoms. It is also supported by the fact that amphetamines, which trigger the release of dopamine may exacerbate the psychotic symptoms in schizophrenia.[8]

An influential theory, known as the Dopamine hypothesis of schizophrenia, proposed that a malfunction involving dopamine pathways was the cause of (the positive symptoms of) schizophrenia. This theory is now thought to be overly simplistic as a complete explanation, partly because newer antipsychotic medication (called atypical antipsychotic medication) can be equally effective as older medication (called typical antipsychotic medication), but also affects serotonin function and may have slightly less of a dopamine blocking effect.[9]


According to critics, the chemical imbalance hypothesis has been overpromoted and continues to be advanced as factual by pharmaceutical companies.[10] They believe the general population and many journalists have accepted this hypothesis into their understanding of mental illness uncritically.[11] Some academics believe that the advertisements are oversimplified and don't fully explain what is happening.[12]

Recently biologists researching the gut microbiome have begun to form a better explanatory model of the aetiology of mental health disorders as an alternative to the oversimplified chemical imbalance theory and this emerging field is commonly referred to as Nutritional Psychology.[13]

Dr Ronald Pies, the current editor in Chief Emeritus of Psychiatric Times stated in on July 11, 2011 that "In truth, the 'chemical imbalance' notion was always a kind of urban legend—never a theory seriously propounded by well-informed psychiatrists."[14]


  1. ^ Drugs and the Brain: Antidepressants
  2. ^ a b Schildkraut, Joseph (1 November 1965). "The Catecholamine Hypothesis of Affective Disorders: A review of Supporting Evidence". American Journal of Psychiatry 122 (5): 509–22. doi:10.1176/ajp.122.5.509. PMID 5319766. 
  3. ^ a b Schildkraut, Joseph (1 November 1995). "The catecholamine hypothesis of affective disorders: a review of supporting evidence. 1965 [classical article]". Journal of Neuropsychiatry and Clinical Neurosciences 7 (4): 524–533. doi:10.1176/jnp.7.4.524. PMID 8555758. 
  4. ^ Pearce, Jeremy (8 July 2006). "Joseph J. Schildkraut, 72, Brain Chemistry Researcher, Dies". The New York Times. 
  5. ^ a b Johan A Den Boer: Looking Beyond the Monoamine Hypothesis. European Neurological Review, 2006;6(1):87-92
  6. ^ "Television adverts for antidepressants cause anxiety". New Scientist (2525). 12 November 2005. 
  7. ^ "The "Chemical Imbalance" Theory: Dead or Alive?". 14 April 2008. 
  8. ^ Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB (1996). "Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects". Proceedings of the National Academy of Sciences of the USA 93 (17): 9235–40. Bibcode:1996PNAS...93.9235L. doi:10.1073/pnas.93.17.9235. PMC 38625. PMID 8799184. 
  9. ^ Jones HM; Pilowsky LS (2002). "Dopamine and antipsychotic drug action revisited". British Journal of Psychiatry 181 (4): 271–275. doi:10.1192/bjp.181.4.271. PMID 12356650. 
  10. ^ Kirsch, Irving. "Two: The Dirty Little Secret." The Emperor's New Drugs: Exploding the Antidepressant Myth. London: Bodley Head, 2009. 39-40. Print.
  11. ^ Leo, Jonathan; Lacasse, Jeffrey R. (2007). "The Media and the Chemical Imbalance Theory of Depression" (PDF). Society 45 (1): 35. doi:10.1007/s12115-007-9047-3. 
  12. ^ Barclay, Laurie MD (8 November 2005). "Advertisements for SSRIs may be misleading". Medscape. 
  13. ^ Kaplan, B. J., Rucklidge, J. J., Romijn, A., & McLeod, K. (2015). The Emerging Field of Nutritional Mental Health Inflammation, the Microbiome, Oxidative Stress, and Mitochondrial Function. Clinical Psychological Science, 2167702614555413. doi: 10.1177/2167702614555413
  14. ^ "Psychiatry’s New Brain-Mind and the Legend of the Chemical Imbalance” by Ronald W. Pies, MD. July 11, 2011.