Furthermore, several studies have suggested that the use of Psychostimulant drugs (such as amphetamines and cocaine), which work by enhancing dopamine neurotransmission, have been shown to induce psychotic symptoms such as hallucinations, delusions and disorganised speech and thinking, all of which demonstrate a marked resemblance to the positive symptoms exhibited in patients with Paranoid Schizophrenia (Laruelle, et al., 1996; Breier, et al., 1997; Abi-Dargham, et al., 1998).
Although some research has implicated excess dopamine as a possible cause of schizophrenia, there is still much controversy surrounding this theory. It could be argued that the theory is reliable because research demonstrates that alterations in levels of dopamine either exacerbate or reduce symptoms, however, there are limitations with this theory, as blocking of the dopamine D2 receptor sites will only have an impact on the positive symptoms of schizophrenia, and not the negative symptoms such as apathy, speech and working memory, which are associated with the mesocortical pathway (Wayandt, 2006: 130). It has been suggested by Stahl (2008), that the reason for this may be, that unlike the mesolimbic pathway which is hyperactive in dopamine, the mesocortical pathway may already be deficient in dopamine, therefore blocking of the D2 receptors in the mesocortical pathway could further increase negative symptoms.
Swerdlow (2010: 359) suggests that an argument against the dopamine hypothesis may be that some patients may be unresponsive to the more traditional neuroleptic drugs such as chlorpromazine which acts upon the D2 receptor sites. However, studies conducted by Brier and Buchanan (1996) on the use of a new atypical anti-psychotic drug called clozapine, claimed to show a 40-60% improvement in symptoms for patients of schizophrenia who did not respond to the traditional neuroleptics (Pincus & Tucker, 2003: 119). Clozapine still plays a role in blocking the D2 receptor site but with less intensity than traditional antipsychotics. However, it is also responsible for blocking a variety of other receptor sites including dopamine D4, 5-HT (serotonin), norepinephrine, acetylcholine, and histamine (Moses, 2012). With this in mind, it could be said that dopamine does not operate in isolation, and may form only part of the etiology in the manifestation of Schizophrenia.
What is clear is that the dopamine theory is far from conclusive, which would suggest that much more research is needed to examine the role that other neurotransmitters may play in the disorder. Furthermore, if dopamine does play a primary role in schizophrenia then this leads us to the question, what causes this dysfunction in the dopamine neurotransmitters?
Studies to date have identified that several of the genes which are closely linked with Schizophrenia are directly involved in dopaminergic pathways (Howes & Kapur, 2009); this therefore leads us to a further conclusion that genetics and gene mutation may play a key role in the development of schizophrenia. Evidence suggests that there is a strong genetic predisposition to developing the disorder and the more closely someone is related to an individual with Schizophrenia, the higher the chance of them developing the disorder themselves (Nolen-Hesksema, et al., 2009).
Family, Twin and adoption studies demonstrate that there are higher concordance rates between monozygotic (Identical) twins than there is with dizygotic (non-identical) twins. Studies conducted by Gotteman (1991) found that dizygotic twins had a 17% risk factor if their twin sibling had the disorder; however, for monozygotic twins, the rate increased to a more significant 48%. Further studies have revealed that children of schizophrenic parents showed similar concordance rates of 46%, however, children born to schizophrenic mothers but adopted by non-schizophrenic mothers only showed a risk factor of 17% (Kalat, 2009: 451). These findings suggest that Schizophrenia is not entirely genetic, and that environmental factors may also play a role in the development of the disorder. However, in giving strength to the genetic theory, new research in epigenetics has found that, whilst monozygotic twins share the same DNA, there are variations in the levels of methylation detected in a gene called ST6GALNAC1, which has been found in individual schizophrenic twins (Times, 2011). Whilst these changes in segments of DNA offer some explanations for the discordance in monozygotic twin studies in Schizophrenia, it is suggested that these mutations develop as a result of environmental influences (Coghlan, 2011: 16).
Moving on, it has become apparent, that both dopamine and genetics play an important role in the predisposition towards schizophrenia. However, evidence appears to suggest that, whilst an individual may have a predisposition, this is not a guarantee that they will develop the disorder. Theorists believe that for those individuals who do have a predisposition towards schizophrenia, environmental factors can greatly influence the development and life course of the condition.
One environmental factor which may be linked to the dopamine theory is the associated risk between prenatal exposure to viral infections and adult onset of schizophrenia (Psychiatry, 2011). Research suggests that prenatal environmental insults such as viral induced anaemia in the first and second trimesters, may lead to deficiency in myelination of neurons and dysfunction in the dopaminergic pathways (Brown, 2011). In support of this claim, a study by (Aguilar-Valles, et al., 2010) used rat models to produce viral induced iron deficiency, and found that the biochemical and behavioural changes which occurred in the rats were characteristic of those found in adult schizophrenia.
Moreover, Brown (2011) also suggests that iron deficiency significantly contributes to de novo mutations in DNA, and this may be due to a possible disruption of oxidation in the cells. Consequently, researchers have also identified significant representation of de novo mutations in Schizophrenics (Krebs & Rouleau, 2011). De novo mutations do not occur as a result of hereditary factors, but instead, are alterations which take place around the time of early conception (Reference, 2012). These findings may support the theory that prenatal environmental insults could be responsible for the increased risk in someone developing the disorder. Furthermore, this may also offer some explanation for the manifestation of schizophrenia in individuals who have no family history of the disorder.
In conclusion, schizophrenia still remains one of the most perplexing and misunderstood disorders faced by mental health professionals. It is evident that dopamine, genetics and the environment all play a role in schizophrenia, however not one of these factors appears to work in isolation. In short, it would appear that the environment interacts with both biochemical and genetic factors and determines whether or not an individual is likely to develop the disorder.
Reference List
Abi-Dargham, A. et al., 1998. Increased striatal dopamine transmission in schizophrenia: Confirmation in a second cohort. American Journal Of Psychiatry, 155(6), p. 761.
Aguilar-Valles, A., Flores, C. & Luheshi, G. N., 2010. Prenatal Inflammation-Induced Hypoferremia Alters Dopamine Function in the Adult Offspring in Rat: Relevance for Schizophrenia. PLos ONE, 5(6), pp. 1-12.
Breier, A. et al., 1997. Schizophrenia is Associated with Elevated Amphetamine-Induced Synaptic Dopamine Concentrations: Evidence from a Novel Positron Emission Tomography Method. Proceedings of the National Academy of Sciences of the United States of America, Volume 94, pp. 2569-2574.
Brown, A. S., 2011. The environment and susceptibility to schizophrenia. Progress in Neurobiology, 93(1), pp. 23-58.
Coghlan, A., 2011. 'Twins' genes hint at origins of psychosis. New Scientist, 212(2832), p. 16.
Howes, O. D. & Kapur, S., 2009. The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common. Schizophrenia Bulletin, 35(3), pp. 549-562.
Kalat, J. W., 2009. Biological Psychology. 10th ed. Belmont, California: Wadsworth, Cengage Learning.
Krebs, M.-O. & Rouleau, G., 2011. Increased exonic de novo mutation rate in individuals with schizophrenia. Nature Genetics, 10 July , Issue 43, pp. 860-863.
Laruelle, M. et al., 1996. Single Photon Emission Computerized Tomography Imaging of Amphetamine-Induced Dopamine Release in Drug-Free Schizophrenic. Proceedings of the National Academy of Sciences of the United States of America, 93(17), pp. 9235-9240.
Moses, S., 2012. Family Practice Notebook, LCC. [Online]
Available at: http://www.fpnotebook.com/psych/pharm/Clzpn.htm
[Accessed 19 11 2012].
Nolen-Hesksema, S., Fredrickson, B. L. & Geoff R Loftus, W. A. W., 2009. Atkinson & Hilgard's Introduction to Psychology. 15th ed. Andover, Hampshire: Cengage Learning EMEA.
Norman, I., 2004. The Art and Science of Mental Health Nursing. Berkshire, England: Open University Press.
Pincus, J. H. & Tucker, G. J., 2003. Behavioral Neurology. 4th Edition ed. New York: Oxford University Press.
Psychiatry, F. i., 2011. PMC U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).. [Online]
Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222883/
[Accessed 24 November 2012].
Reference, G. H., 2012. Genetics Home Reference. [Online]
Available at: http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/genemutation
[Accessed 25 November 2012].
Seeman, P., 2011. All Roads to Schizophrenia lead to Dopamine Supersensitiviy and Elevated Dopamine D2. CNS Neuroscience & Theraputics, Volume 17, pp. 118-132.
Stahl, S. M., 2002. Essential Psychopharmacology of Antipsychotics and Mood Stabilizers. Cambridge: Cambridge University Press.
Stahl, S. M., 2008. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York: Cambridge University Press.
Swerdlow, N. R., 2010. Behavioral Neurobiology of Schizophrenia and Its Treatment. Heidelberg: Springer-Verlag.
Taylor, V., 2011. www.schizophrenia.com. [Online]
Available at: http://www.schizophrenic.com/articles/schizophrenia/meaning-schizophrenic
[Accessed August 2011].
Times, I. B., 2011. Epigenetic To Solve Schizophrenia and Bipolar Disorder Mysteries?. International Business Times, 30 September.
Wayandt, L. L., 2006. The Physiological Bases of Cognitive and Behavioral Disorders. Mahwah, New Jersery: s.n.