Dopamine: Schizophrenia and Parkinson's disorder.

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Dopamine and its Relationship to Parkinson’s Disorder and Schizophrenia


            Dopamine is one of the brain’s neurotransmitters (Carlson, 2013). This neurochemical performs an important role in concepts such as movement and motivation. The purpose of this essay is to explore the many functions of dopamine and its influence on behavior.
            The beginning of the subject of this essay starts when tyrosine is synthesized into dopamine (Cumming, 2009). Dopamine has been placed in the category of monoamines and in the subcategory of catecholamines, which is a class of amines that includes the above mentioned neurotransmitter, norepinephrine, and epinephrine. Moreover, the chemical Tyrosine hydroxylase is the enzyme (a catalyst that either breaks or combines components (Encyclopædia Britannica, n. d.)) involved in the biosynthesis of catecholamines (Kuhar, Couceyro, Lambert, n. d.). Its cofactor is biopterin, which is a common cofactor for enzymes, and uses molecular oxygen and tyrosine as its substrates.
 After Tyrosine, which is an amino acid, receives an oxygen and a hydrogen atom it becomes L-DOPA (Carlson, 2013). DOPA decarboxylase, which is another enzyme, removes the carboxyl group from DOPA in order for it to become dopamine (Kuhar et al., n. d.). Later, dopamine β-hydroxylase is used to synthesize epinephrine or norepinephrine, but for the purpose of this essay we are going to stop in the biosynthesis process here.

 

The image above shows the chemical structure of tyrosine. When tyrosine hydroxylase converts tyrosine into L-Dopa the structure changes and ends up looking like the structure below.

After DOPA decarboxylase acts upon L-Dopa, the following changes in the chemical structure take place., thus, becoming dopamine.

       The most important dopaminergic neurons are in the substantia nigra and ventral tegmental area (Carlson, 2012). The former and the latter are in the midbrain. It has been calculated that the dopamine cells in the substantia nigra measure on average 50 μm (Cumming, 2009). The measure that was just mentioned refers to the idea of a micrometer, or the millionth of a meter. In addition, they are usually pigmented, which is caused by neuromelanin granules in the cytoplasm of the cell. Moreover, it has been calculated that there are around 300, 500 dopamine neurons in each side of the substantia nigra and that around 8% is lost per decade due to aging (Cabello et al. 2002).

            The physiology of dopamine neurons is similar to other neurons. For example, they are polarized at -70mV and this is kept this way by the activity of sodium and potassium (Cumming, 2009). Nevertheless, something different is how they temporarily increase dopamine release by firing in bursts, which depends on the depolarization of the neurons (Grace, 1991). The dopaminergic cells mentioned in the paragraph above have their axons pointed towards the neostriatum, which has been accredited to be involved in movement. Another connection that involves movement is between the substantia nigra and the corpus striatum. This is why dopamine cells are connected with Parkinson’s disease. According to the National Institute of Health, when the neurons mentioned above die or become impaired there is less dopamine in the central nervous system, and this is what lead individuals to develop Parkinson’s disease (National Institute of Health, n. d.).

            In fact, it is possible to induce Parkinson’s disorder. Researchers, specifically biopsychologists, are able to explore more about the disease once it is induced in rats. One way of performing this technique is by intracerebral injections of the dopamine analog 6-hydroxydopamine (6-OHDA). This is a neurotoxin that damages dopamine pathways (Hanrott et al., 2005). Another way in which Parkinson’s disease can be induced is when MPTP, or meperidine analog 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, enters the blood-brain barrier. This causes dopaminergic neurons to be poisoned and asphyxiate from the inside (Cummings, 2009).

            Another mental illness that is affected by dopamine is schizophrenia. One of the first connections discovered between dopamine and schizophrenia was with the use of chlorpromazine in 1952 (Ban, 2007). This drug was used by psychiatrists mainly to treat anxiety, however, it was also given to psychotic patients. It was not really efficient in the former, but it was for the latter. This happened because chlorpromazine is a dopamine antagonist, specifically it blocks D2 and D3 dopamine receptors (Carlson, 2012).

If dopamine antagonists are able to remove positive symptoms, then, people that are not schizophrenic would experience them after consuming agonists. This happens when individuals consume drugs such as amphetamine, cocaine, or L-Dopa. The first two block reuptake and the last one stimulates the synthesis of dopamine.

            The use of a dopamine antagonist used to treat psychosis and the idea that dopamine was also a neurotransmitter, and not only a precursor for norepinephrine, strengthen the idea that hyperactivity of dopamine was the cause of schizophrenia, at least for the positive symptoms (Brisch et al., 2014). There are three classifications of schizophrenic symptoms. They are positive, negative, and negative. The first category are symptoms that add something to the individual. This includes delusions, which are false ideals (Delusions, 2016), hallucinations, which are perceptions that are not real (Hallucinations, 2016), and thought disorders, which refer to a confusion in cognition (Thought-disorder, 2016). The negative symptoms refer to an absence or the decrease of a behavior. This includes being socially withdrawn, lack of affect, and reduced motivation (Carlson, 2012). The last category, which is cognitive symptoms, refers to those that add distortion to thinking. These symptoms include problems in memory, attention, learning, and problem solving (Carlson, 2012).

The Three Categories of Symptoms in Schizophrenia

Negative Symptoms
Social Withdrawal
Lack of Affect
Anhedonia
Positive Symptoms
Hallucinations
Delusions
Thought-disorders
Cognitive Symptoms
Problems in Attention
Problems in Learning
Problems in Memory

            The hyperactivity of dopamine theory does not only mean that there is an excess of dopamine, but it can also indicate that the dopaminergic receptors are hypersensitive. This happens for several reasons. One of them is that because D2 dopamine receptors are blocked, usually because of anti-psychotic medication, their affinity increases (Seeman et al., 2014). All of the statements above are related to hyperactivity of dopamine and its relation to positive symptoms. However, the cause of the negative ones has not been explained.

Neurological damage is the believed cause, or at least the most supported theory, for the negative symptoms of schizophrenia. There are several reasons that support this fact. The first one is the similitude between other disorders that are caused by brain damage and the negative symptoms that are present in schizophrenics (Hall, 1998). The evidence of damage to the brain is seen in the large ventricles, which are spaces in the forebrain and brainstem that if large indicate loss of brain tissue (Purves, 2001), that are shown on computerized tomographic (CT) scans. The symptoms that are found in people with large ventricles, not only schizophrenics with negative symptoms, include catatonia, which is a lack of movement (Catatonia, 2016), and poor visual pursuit, which is a lack of ability in following an object with the eyes (Visual Pursuit, 2016).

            Usually, the damage has to occur in the prefrontal cortex in order for negative symptoms to be present (Hall, 1998). Other individuals that have damage in the same areas of the brain perform similarly to schizophrenics in the Wisconsin Card Sorting Test (WCST) (Everett et al., 2001). This test involves sorting cards into three categories: shape, color, and number of figures. If an individual shows no problems in arranging cards into one category, but presents difficulty when asked to change the classification, they would be categorized as being behaviorally inflexible. This refers to the notion that an individual or an animal can or cannot adapt their behavior (Brown & Tait, 2014).

            In addition, it is possible for an individual to present both types of symptoms. This involves both theories, the neurological damage in the prefrontal cortex and hyperactivity of dopamine or hypersensitivity of dopaminergic receptors, working together. This would mean that the brain damage that causes the negative symptoms is actually harming neurons that inhibit dopamine release, and thus causing the hyperactivity of dopamine.





References

Ban, T. A. (2007). Fifty years chlorpromazine: a historical perspective. Neuropsychiatric Disease and Treatment, 3(4), 495–500.
Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H.-G., Steiner, J., … Gos, T. (2014). The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue. Frontiers in Psychiatry, 5, 47. http://doi.org/10.3389/fpsyt.2014.00047
Brown, V., & Tait, D. (2014). Behavioral Flexibility: Attentional Shifting, Rule Switching and Response Reversal. Springer Reference. doi:10.1007/springerreference_169297
Cabello, C. R., Thune, J. J., Pakkenberg H., & Pakkenberg, B. 2002, “Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophy”, Neuropathol. Appl. Neurobiol., vol 28, no. 4, pp. 283-291.
Carlson, N. R. (2012). Physiology of behavior (11th ed.).
Catatonic. (2016). Retrieved from http://www.dictionary.com/browse/catatonic.
Cumming, P. (2009). Imaging dopamine. Cambridge, UK: Cambridge University Press.
Delusions. (2016). Retrieved from http://www.merriam-webster.com/dictionary/delusion
Encyclopædia Britannica. (n.d.). Enzyme. Retrieved March 20, 2016, from http://www.britannica.com/science/enzyme
Everett, J., Lavoie, K., Gagnon, J. F., & Gosselin, N. (2001). Performance of patients with schizophrenia on the Wisconsin Card Sorting Test (WCST). Journal of Psychiatry and Neuroscience, 26(2), 123–130.
Grace, A. A. (1991). “Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia,” Neuroscience, Vol. 10, no. 2, pp. 333-348.
Hall, R. (1998). Potential Causes of Schizophrenia. Retrieved from http://web.mst.edu/~rhall/neuroscience/07_disorders/schizo_cause.pdf
Hallucinations (2016). Retrieved from http://www.merriam-webster.com/dictionary/hallucinations
Hanrott, K., Gudmensen, L., O'Neill, M., & Wonnacott, S. (2005). 6-Hydroxydopamine-induced Apoptosis Is Mediated via Extracellular Auto-oxidation and Caspase 3-dependent Activation of Protein Kinase C. Journal of Biological Chemidstry, 281(9), 5373-5382. doi:10.1074/jbc.m511560200
Kuhar, M. J., Couceyro, P. R., & Lambert, P. D. (n.d.). Biosynthesis of Catecholamines. Retrieved March 20, 2016, from http://www.ncbi.nlm.nih.gov/books/NBK27988/
National Institute of Health. (n.d.). Parkinson's Disease. Retrieved from http://nihseniorhealth.gov/parkinsonsdisease/whatcausesparkinsonsdisease/01.html
Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates. (2001). The Ventricular System.Available from: http://www.ncbi.nlm.nih.gov/books/NBK11083/
Seeman, M. V., & Seeman, P. (2014). Is schizophrenia a dopamine supersensitivity psychotic reaction? Progress in Neuro-Psychopharmacology & Biological Psychiatry, 0, 10.1016/j.pnpbp.2013.10.003. http://doi.org/10.1016/j.pnpbp.2013.10.003
Thought-disorder. (2016). Retrieved from http://www.dictionary.com/browse/thought-disorder.

Visual Pursuit. (2016). Retrieved from http://psychologydictionary.org/visual-pursuit/.

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