Chemical imbalance

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

The basic concept is 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 depression.^[1] These findings and other supporting evidence led Joseph Schildkraut to publish his paper called "The Catecholamine Hypothesis of Affective Disorders" in 1965.^[2] 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^[3] and led to the development of new classes of drugs such as SSRIs (selective-serotonin reuptake inhibitors).^[4]

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.^[3][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] Recently, psychiatrist Peter Kramer stated that the serotonin theory of depression had been declared dead prematurely.^[7] Kramer argues that recent scientific research actually shows a definitive role for serotonin deficiency in depression. An analysis of the studies Kramer cites argues that such statements are premature.^[8]

Monoamine hypothesis

Main article: Biology of depression#Monoamine hypothesis

The Monoamine hypothesis is a biological theory 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.^[2] 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.

The hypothesis has been a major focus of research in the fields pathophysiology and pharmacotherapy for over 25 years.^[3] and led to the development of new classes of drugs such as SSRIs (selective serotonin reuptake inhibitors).^[4]

Dopamine hypothesis

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.^[9]

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.^[10]

Criticisms

According to critics, the chemical imbalance hypothesis has been overpromoted and continues to be advanced as factual by pharmaceutical companies. They believe the general population and many journalists have accepted this hypothesis into their understanding of mental illness uncritically.^[11] They have pointed to the lack of an established chemical balance (without which, they claim, the notion of an "imbalance" is meaningless). Certain pharmaceutical companies such as Pfizer continue to promote drugs like Zoloft with advertisements asserting that mental illness may be due to chemical imbalances in the brain, and that their drugs work to "correct" this imbalance.^[12] Most academics believe that the advertisements are oversimplified and don't fully explain what is happening.^[13]

Chemical imbalances theories do not presume individual laboratory tests be obtained from a patient at the time of prescription, such as one would expect in the analogy to physical medicine. For example, someone suffering from schizophrenia is not given haloperidol on the basis of a laboratory test which shows that his or her dopamine level is too high.

Chemical imbalances theories distinguish, between "side" and "main" drug effects in recording the response to the drug. "Side" effects are considered to be simple, direct, predictable, allowable effects which are merely "physical" but do include often flattened affect and memory, emotive and cognitive effects. These drug effects may then be cited capriciously as further evidence to confirm the diagnosis as correct, confusing cause and effect.^{[citation needed]}

When "improvement" is measured in industry research studies, attention is given only to the "main" effect—typically a complex, indirect, interpersonal, perceptual, cultural change, thereby confusing cause with coincidence. There does not exist in chemical imbalance theories, effectiveness measures using standard social networks and associated tests before and after drug administration.^{[citation needed]}

Chemical imbalance theories predominate in "streamline" public sector medicine for lower social class and homeless persons, where drugs constitute the only form of treatment. There is much wishful thinking in attribution of drug effect, particularly in cases like schizophrenia, where there no longer exists a patient [non-drug user] control group available.^{[citation needed]}

One criticism while not outright rejecting the theory is that it has been scientifically proven that things other than drugs can influence brain chemistry. Exercise releases endorphins. Even our own thoughts change our brain chemistry. These natural methods of changing brain chemicals are claimed by critics to be preferable to drugs since drugs have side effects. Furthermore, some psychiatric drugs might alter the mind by disabling moods and emotions not just in circumstances where they're a problem but in circumstances where they're appropriate or even beneficial as well while natural ways to change brain chemistry can be used as needed.

See also

• BDNF
• Anatomy of an Epidemic

References

1. ^ Drugs and the Brain: Antidepressants
2. ^ ^{a b} The catecholamine hypothesis of affective disorders: a review of supporting evidence. 1965 [classical article] - Schildkraut 7 (4): 524 - J Neuropsychiatry Clin Neurosci
3. ^ ^{a b c} Looking Beyond the Monoamine Hypothesis
4. ^ ^{a b} Mental Illness - GSU Biology 4102 / 6102
5. ^ The Catecholamine Hypothesis of Affective Disorders: A review of Supporting Evidence - Schildkraut 122 (5): 509 - Am J Psychiatry
6. ^ Television adverts for antidepressants cause anxiety, from New Scientist. Published November 12, 2005; accessed November 17, 2007.
7. ^ http://blogs.psychologytoday.com/blog/in-practice/200804/the-chemical-imbalance-theory-dead-or-alive The "Chemical Imbalance" Theory: Dead or Alive?
8. ^ http://chemicalimbalance.org/?p=6 Is Clinical Depression Caused by a Serotonin Imbalance? A Response to Peter Kramer.
9. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38625. 
10. ^ 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. 
11. ^ Leo, Jonathan; Lacasse, Jeffrey R. (2007). "The Media and the Chemical Imbalance Theory of Depression". Society 45 (1): 35. doi:10.1007/s12115-007-9047-3. http://www.springerlink.com/content/u37j12152n826q60/fulltext.pdf. 
12. ^ Lacasse JR, Leo J (2005 Dec). "Serotonin and depression: a disconnect between the advertisements and the scientific literature". PLoS Medicine 2 (12): e392. doi:10.1371/journal.pmed.0020392. PMC 1277931. PMID 16268734. http://medicine.plosjournals.org/archive/1549-1676/2/12/pdf/10.1371_journal.pmed.0020392-L.pdf. 
13. ^ "Advertisements for SSRIs may be misleading". http://www.medscape.com/viewarticle/516262.