Schizophrenia is a severe mental illness that affects an individual’s ability to function normally. The symptoms of schizophrenia resemble the symptoms of psychosis; however psychosis is not a defining feature of schizophrenia. According to the DSM-IV-TR the symptom characteristics of schizophrenia can be described as comprising cognitive and emotional dysfunctions that include dysfunctions of perception, inferential thinking, language and communication, behaviour monitoring, affect, fluency, productivity of thought and speech and attention (Davey, 2008).
Over the past 5 decades there has been a vast amount of research on the etiological causes of schizophrenia, involving Psychological, Biological, Social and Cognitive factors. Some researchers would argue that schizophrenia is mainly due to biology; however there are still aspects of biology that are argued to be more specific than others. Schizophrenia is widely believed to have a neurobiological basis in which a number of neurotransmitters are thought to play a role in the symptoms of schizophrenia in the brain. This has resulted in the production of many hypotheses for the cause of schizophrenia. The biochemical theory of schizophrenia that has been the most prominent for many years is known as the dopamine hypothesis. This theory argues that the symptoms of schizophrenia are related to the increased level or excessive amount of dopamine neurotransmitter in the brain. The dopamine theory originated from observations of the dopamine-blocking actions of early neuroleptic or antipsychotic drugs (Moncrieff, 2009) in which pharmacological evidence indicated, drugs that decrease the dopamine activity such as phenothiazines are antipsychotic and drugs that promote dopamine action such as amphetamine are psychotominmetic. Schneider and Deldin (2001) claimed that antipsychotic drugs act by blocking the brain’s dopamine receptor sites therefore reducing dopamine activity. However the problem with the antipsychotic drugs is that it only alleviates the positive symptoms of schizophrenia thus a possible criticism for the dopamine hypothesis is that it does not solve the problem of the negative symptoms. According to Thomas (1997) there is much evidence to suggest that negative symptoms are associated with reduced dopamine activity. Also another issue with this theory is that the functions of the neuroleptic drugs produce side effects which induce resembling symptoms of Parkinson’s disease as a result of the reduction of the dopamine levels.
Nevertheless there have been a number of factors that have led to the implication of excess dopamine activity in the brain. Grilly (2002) proposed that when individuals who suffered from Parkinson’s disease, were given the drug L-dopa to increase the level of dopamine, they began to show psychotic symptoms. Therefore this may suggest strong evidence towards high levels of dopamine or excess dopamine in the brain, being responsible for many of the symptoms of psychosis. However research by Bradford (2009) found that low levels of glutamate in the cerebrospinal fluid in the brain is involved in the development of schizophrenia involving phencyclidine and ketamine. Together they have been shown to induce psychosis in humans that closely resembles schizophrenia and are representative of not only the positive symptoms and cognitive defects of the disease but also in part the negative symptoms.
On the contrary another support to the dopamine hypothesis is the link between excessive use of amphetamines and symptoms of psychosis. According to Angrist et al. (1974) these symptoms include paranoia and repetitive, stereotyped behaviour patterns. The function of amphetamine drugs is to increase the level of dopamine activity; therefore giving this drug to Schizophrenics would increase the severity of the symptoms. However as mentioned previously, giving antipsychotic drugs such as phenothiazines reverses the effects of drugs such as amphetamines in non-schizophrenics. Therefore this gives great support for the dopamine hypothesis in that dopamine levels influences the intensity of schizophrenic symptoms. However many researchers such as Carlsson (2001) have found that although antipsychotics are usually effective in dealing with the positive symptoms of schizophrenia, they do not start having an effect until about 6 weeks after the treatment has commenced. This seems peculiar as past research has found these drugs to start blocking dopamine receptors in the brain immediately.
Other research on brain imaging studies have also indicated that individuals diagnosed with schizophrenia show excessive levels of dopamine released from areas of the brain such as the basal ganglia – especially when biochemical precursors to dopamine such as L-dopa are administered to the individual (Carlsson, 2001).
Post-mortem findings by Seeman and Kapur (2001) have involved an increased level of dopamine and significantly more dopamine receptors in the brains of deceased schizophrenic sufferers, especially in the limbic areas of the brain. Owen et al (1986) found the same results however in his study on post-mortems; he established that the patients had been on antipsychotic drugs for many years. Wong et al. (1986) on the other hand found that the deceased who suffered from schizophrenia had increased amounts of dopamine receptors but these patients were medication free. Although both these studies give strong evidence for the link between dopamine and schizophrenia, a problem occurs when studies such as these find differences between schizophrenic subjects which appear to be conflicting or inconsistent. Therefore although the dopamine hypothesis gives a good account of the aetiology of schizophrenia, it appears to be incomplete in some aspects of neropsychopharmacology.
A major problem with the dopamine hypothesis is that it only takes into account a single neurotransmitter and therefore does not consider the interaction of other neurotransmitters. For many years, biological research has focussed on the dopamine hypothesis and the effects of antipsychotics in blocking dopamine D2 receptors. It has therefore ignored other hypotheses on neurotransmitters such as glutamate. According to the glutamate hypothesis of schizophrenia, the under-activity of the neurotransmitter glutamate, contributes to psychosis. Therefore to alleviate psychosis, schizophrenia advocates the stimulation of glutamate receptors. Kalat (2007) claims that in many of the brain areas, dopamine inhibits glutamate release or glutamate stimulates neurons that inhibit dopamine release. Therefore an increase in dopamine would produce the same effects as decreased glutamate.
Another major neurotransmitter to play a key role in schizophrenia is that of serotonin. Many researchers have placed emphasis on the role of serotonin whereby the blockage of the receptors by newer antipsychotic drugs, alleviate psychotic symptoms. Iqbal and Van Praag (1995) looked at the effects of compounds such as antipsychotics, blocking serotonin receptors in which they reported potential and established antipsychotic effects. To support this finding, previous several controlled studies found that Ritanserin, a selective serotonin (5HT2a) receptor blocking agent, with no effect on dopamine receptors had been shown to alleviate psychotic symptoms with a preference for negative symptoms (Gelders et al., 1985). However although this research showed positive outcomes much drug development focused on the interaction between dopamine and serotonin of schizophrenia. According to Nordstrom et al. (1995) many new antipsychotic drugs appear to be effective, as not only do they block dopamine receptors but serotonin receptors too. Therefore this has led to many researchers looking into the possibility that psychotic symptoms may not be related to excess dopamine activity alone, but to an interaction between dopamine and serotonin activity. Kahn and Davidson (1993) claimed that preclinical studies have shown that at least some of the clinical effects of neuroleptics may be due to an alteration of interactions between dopamine and serotonin.
Over the years, extensive investigation has given rise to numerous neurochemical hypotheses of the aetiology and pathophysiology of schizophrenia. Dopamine, Glutamate and Serotonin have given significant insight into the cause of schizophrenia, but more emphasis has been placed on dopamine. Schizophrenia is a sufficiently complex disorder but all three neurotransmitters play important roles in this disorder, perhaps to different degrees in different individuals.
Therefore to conclude, although the dopamine hypothesis has been largely researched upon, it is not the only one neurotransmitter to play a key role in schizophrenia. Much research has accentuated the importance of other neurotransmitters such as serotonin and glutamate. The problem with the dopamine hypothesis is that it does not take into account the interactions between different neurotransmitters; therefore it is important to understand that the role of dopamine affects different areas of the brain thus influencing the role of other neurotransmitters.
However the dopamine hypothesis has been the most prevalent theory and neurotransmitter for the etiology of schizophrenia despite its criticisms. Gottesman (1991) quoted that “because the most effective drugs used to treat schizophrenia block dopamine receptors and because agents that make schizophrenia worse increase dopamine levels, the hypothesis has made sense and has had remarkable survival in a rapidly changing bioscience environment”.
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