The Dopamine Hypothesis

The dopamine hypothesis is a long standing explanation for psychosis and schizophrenia.  The theory developed aside the abundance of research into dopamine during the 1960’s and 1970’s which was encouraged by dopamine being recognized as an important neurotransmitter in the brain (Carlsson , Lindqvist, Magnusson, & Waldeck, 1958). It suggests that schizophrenia is the result of an imbalance of the neurotransmitter dopamine, which is related to the brains reward and pleasure pathways. Individuals with schizophrenia have been found to have abnormally high numbers of D² receptors on their neurone synapses leading to increased neurone firing and thus higher levels of dopamine. Van Rossum (1966) suggested the theory of schizophrenia and psychosis is the result of over active dopamine pathways in the brain. His research provided evidence that neuroleptic drugs block dopamine receptors in the central nervous system indicating that these drugs are successful due to their ability to reduce levels of dopamine (Van Rossum, 1966).

Supporting research includes antipsychotic drugs, such as thorazine and haldol, which reduce psychotic symptoms by blocking dopamine activity in the brain. (gleitman, Gross & Reisberg, 2011).Van Rossum and Hurkmans (1964) showed that the psychomotor stimulating effects of dexamphetamine and cocaine were due to direct and/or indirect stimulation of dopamine receptors suggesting a link between psychotic behaviour and dopamine. Temporary psychosis has been induced in mentally sound individuals when over dosing on high amounts of amphetamines (of which stimulate dopamine activity) (gleitman, Gross & Reisberg, 2011).  Also, evidence derives from individuals with Parkinsons disease as many are found to have low levels of dopamine. Individuals that were given the drug L-dopa, that increases dopamine levels, were found to develop symptoms similar to that of schizophrenia (Grilly, 2002).

However, more current research suggests that the symptoms of schizophrenia are more likely to be influenced by both deficits and excesses of dopamine in the brain rather than merely over active dopamine production (Abi-Dargham, 2004).  The updated dopamine hypothesis indicates that there is a co-existing deficit of dopamine in the cortex and an excess in the sub cortex of individuals with schizophrenia (Abi-Dargham, 2004). The revised theory is still not conclusive as other neurotransmitters have also been found to produce schizophrenic type symptoms such as glutamate. The blockage of glutamate receptors by the illegal drug Phencyclidine induces schizophrenic-like symptoms (Gorelick & Balster, 1995). Also, the increase in glutamate levels has been found to alleviate positive and negative symptoms of schizophrenia (Goff & Coyle, 2001).

Therefore this suggests that the dopamine hypothesis is too basic to explain schizophrenia and rather a theory that incorporates the effect of a variety of neurotransmitters and/or their pathways is more plausible.

 

 References

Abi-Dargham, A. (2004). Do we still believe in the dopamine hypothesis? New data bring new evidence. International Journal of Neuropsychopharmacology, 7(1), 1-5. doi: 10.1017/S1461145704004110

Carlsson A, Lindqvist T, Magnusson T, Waldeck B. (1958). On the presence of 3-hydroxytyramine in brain. Science, 127, 471.

Gorelick, D. A., & Balster, R. L. (1995). Phencyclidine (PCP). In F. E. Bloom & R. L. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 1767-1776). New York: Raven Press.

Goff, D.C., & Coyle, J.T. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry, 158, 1367–1377.

Gleitman, H., Gross, J., Reisberg, D. (2011). Psychopathology. In Snavley, S. L. (8. Ed.) Psychology Eighth Edition (pp 664-666). New York, London: Norton & Company, Inc.

Grilly, D. M. (2002). Drugs and human behavior. Boston: Allyn & Bacon.

Van Rossum JM, Hurkmans JAThM (1964) Mechanism of action of psychomotor stimulant drugs. Significance of dopamine in locomotor stimulant action. International Journal Neuropharmacology,  3, 227-239.

Van Rossum, J. M. (1966). The significance of dopamine-receptor blockade for the action of neuroleptic drugs. In: Excerpta Medica International Congress Series No. 129 Proceedings of The Vth International Congress of The Collegium Internationale Neuropsychopharmacologicum Washington, 28-31, 321-329.

4 thoughts on “The Dopamine Hypothesis

  1. rebec93 says:

    It has been argued that pharmaceutical companies have inappropriately pushed forward the dopamine hypothesis of schizophrenia as an intentional and calculated simplification for the sole benefits of the drug marketing industry (Healey 2002). There has also been research that suggests a number of structural causes of schizophrenia, situating around changes in grey matter density in the frontal and temporal lobes (Seeman et al 2005). The dopamine hypothesis is definitely too simple to be seen as the main explanation of schizophrenia with all the mounting research suggesting otherwise and opening new doors to alternative reasons for schizophrenia and psychosis.
    Healey, D.(2002) The Creation of Psychopharmacology. Harvard University Press.

    Seeman, P. Weinshenker, D. Quirion, R. Srivastava, L. K. Bhardwaj, S. K. Grandy, D. K. Premont, R. T. Sotnikova, T. D. Boksa, P. El-Ghundi, M. O’Dowd, B. F. George, S. R. Perreault, M. L. Mannisto, P. T. Robinson, S. Palmitter, R. D. Tallerico, T. (2005) Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. PNAS March 1, 2005 vol. 102 no. 9 3513-3518. DOI:10.1073/pnas.0409766102

  2. rlrom says:

    Although the dopamine hypothesis does have a lot of evidence to support the theory it still doesn’t explain why many schizophrenic patients have enlarged ventricles in the brain (Pahl, Swayze, & Andreasen, 1990). Furthermore it does not explain why there is such a big gap (several weeks) between taking neuroleptic medications and seeing an actual result; surely if it is having too much or too little dopamine the drugs should have a much quicker effect after consumption? Barlow & Durand (1995) suggest that both serotonin play a role. Also in some case neuroleptics have no effect at all. So all in all I would agree with your conclusion that the dopamine hypothesis is too simplistic.

    Barlow, D. H., & Durand, V. M. (1995). Abnormal psychology: An integrative approach. New York: Brooks/Cole.

    Pahl, J. J., Swayze, V. W., & Andreasen, N. C. (1990). Diagnostic advances in anatomical and functional brain imaging in scizophrenia. In A. Kales, C. N. Stefanis, & J. A. Talbot (Eds.), Recent advances in schizophrenia. New York: Springer-Verlag.

    • sophpsych says:

      In relation to the enlarged ventricles, research has suggested that it may a result of taking antipsychotic medication. Lyon et al. (1981) found that as the dose of medication increased, the density of brain tissue decreased leading to enlarged ventricles. Supporting evidence is also provided by enlarged ventricles not being solely related to schizophrenia, individuals with bi-polar and schizoaffective disorders have also been found to have larger than average ventricles (Roy et al. (1998). Bi-polar and schizoaffective individuals also being prescribed similar medication suggests that this is a valid theory.

      Lyon, K., Wilson, J., Golden, C. J., Graber, B., Coffman, J. & Bloch,
      S. (1981). Effects of long-term neuroleptic use on brain density.
      Psychiatry Research 5, 33- 37.

      Roy, P. D., Zipursky, R. B., Saint-Cyr, J. A., Bury, A., Langevin, R., & Seeman, M.V. (1998). Temporal horn enlargement is present in schizophrenia and bipolar disorder. Biological Psychiatry, 44, 418–422. doi: 10.1016/s0006-3223(98)00105-x

      Jones, P. B., Harvey, I., & Lewis, S. W. (1994). Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis. Psychological Medicine, 24, 995–1011.

  3. An interesting and well-argued blog and I agree that the explanation is a little simplistic, as if this were the only cause of Schizophrenia then it should be much more easily treated than it is, Haracz, (1982) commented that “No comprehensive biological scheme has yet been proposed to draw together the genetic, environmental, and clinical features of schizophrenia” and while dopamine may well play a part in the ways in which a person is affected by Schizoid type illnesses there are many other factors which could also be contributing to the development and persistence of the condition.

    Even if we focus on a purely biological explanation for the condition, several studies have shown that many drugs such as ketamine, MDMA and PCP, can induce psychosis and symptoms similar to Schizophrenia. In examining this Jentsch & Roth (1999) suggest the effects on dopamine transmission in testing of such substances are not matched with similar reductions in other neurotransmitters such as noradrenaline and serotonin, but they do show similar alterations in glutamatergic and GABAergic function both of which have also been suggested have an effect on the development of psychosis.

    Schizophrenia is a complicated condition and I do not think there is a simple explanation as to why this develops, as research gos further it is likely that we will identify several types of Schizophrenia each with a different trigger and once this has been accomplished then perhaps we can get more tailored treatments which would be more effective.

    References:
    Haracz, J.L. (1982) The Dopamine Hypothesis An Overview of Studies With Schizophrenic Patients Schizophrenia Bulletin 8 (3) 438-469 Retrieved from: http://www.psycontent.com/content/03705630222l5314/

    Jentsch, J.D & Roth, R.H. (1999) The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia, Neuropsychopharmacology 20, (3),201–225 http://dx.doi.org/10.1016/S0893-133X(98)00060-8

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