Controversies about the Dopamine Hypothesis of Schizophrenia - Research Paper Example

?Running Head: Psychology The Dopamine Hypothesis of Schizophrenia: Issues, Questions, and Controversy Essay of Submission Abstract The dopamine hypothesis of schizophrenia remains inconclusive thus far. Numerous studies have attempted to prove that excessive production of dopamine causes schizophrenia. Only a few were able to find evidence for the dopamine hypothesis but still failed to account for the reliability of their findings. A ‘modified’ version of the dopamine hypothesis has been presented to resolve the inconsistencies and weaknesses of the original theory. Yet, even the modified version received hard criticisms from scholars and clinicians alike. All the same, even though largely criticized, the dopamine hypothesis remains widely recognized in the pharmacological field and pharmaceutical industry. This essay presents an overview of the fundamental issues, questions, and controversies about the dopamine hypothesis of schizophrenia. Introduction Brain functioning and emotions are controlled by the intricate processes of nerve cell networks in the brain. Biochemical theories trying to give an explanation for the development of symptoms of schizophrenia have placed emphasis on defects in the functioning of some nerve cells and other chemical neurotransmitters. The dopamine hypothesis, which is a widely recognized biochemical theory of schizophrenia, states that the core defect could be a relative abnormality in the nerve cell system wherein dopamine is the chemical agent (Stone, Morrison, & Pilowsky, 2007, 441). Severe stress, resulting in an abrupt acceleration in dopamine activity, may bring about schizophrenia, or a psychosis attack, in people at risk. An Overview The dopamine hypothesis of schizophrenia was originally introduced by Van Rossum in 1967 (Malenka, 2009, 405): The hypothesis that neuroleptic drugs may act by blocking dopamine receptors in the brain has been substantiated by preliminary experiments with a few selective and potent neuroleptic drugs. There is an urgent need for a simple isolated tissue that selectively responds to dopamine so that less specific neuroleptic drugs can also be studied and the hypothesis further tested… When the hypothesis of dopamine blockade by neuroleptic agents can be further substantiated it may have fargoing consequences for the pathophysiology of schizophrenia. Over-stimulation of dopamine receptors could then be part of the etiology. As the term ‘dopamine hypothesis’ implies, this theory, basically, explains that the source of schizophrenia is a disproportion in the quantity of dopamine in the brain. Interestingly, the dopamine hypothesis emerged from examining how antipsychotic drugs—its primary type of medication—functioned in the brain’s cortex to reduce delusions and hallucinations (Siegel & Brady, 2011). Antipsychotic drugs were discovered to work in that way by preventing dopamine at its receptor areas. This resulted in the assumption that the brain was generating dopamine above normal quantities. The assumed excessive quantities of dopamine were proof of a neurological dysfunction, thus, consequently, there must be a dopamine dysfunction, and such dysfunction brings about schizophrenia. Arvid Carlson, a Swedish neuroscientist, found out in 1957 that dopamine functioned as a neurotransmitter in the brain (Noll, 2007, 137). Solomon Snyder, on the other hand, made public in 1974 the detection of two forms of dopamine receptors: D -1 and D -2. In addition, he and his associates found out that antipsychotic drugs functioned by connecting only to D -2 receptors. Because every antipsychotic drug functioned by connecting to the D -2 receptors, it was believed that there is an irregularity or defect in the D -2 receptor that brings about psychosis. This became the foundation of the dopamine hypothesis (Noll, 2007, 137). Yet, Snyder eventually moved away from this simplistic theory of schizophrenia and disproved this hypothesis. The dopamine hypothesis was presented and approved without any proof that the dopamine systems of people with schizophrenia are dysfunctional. Soon after, a number of postmortems on people with schizophrenia reported indications of over-active levels of dopamine (Howes & Kapur, 2009). Yet, by that time, it has been reported that the drugs administered to cure schizophrenia not just restrict the production of dopamine, but also trigger a mechanism to balance the restriction. This fundamental premise was elaborated by Snyder (Read, Mosher, & Bentall, 2004, 61): Something within the neuron recognizes this sudden absence of neuro-transmitter molecules at their appropriate receptor site and one way or another transmits a message back to the dopamine neurons saying something like the following: “We don’t have enough dopamine. Please send us some more!” Where upon the dopamine neuron in question proceeds to fire at a more rapid rate. Thus, excessive production of dopamine is stimulated by the drugs that should hypothetically cure the disease, which is believed to be rooted in dopamine system dysfunction. Hence, it is important that studies attempting to prove that the development of schizophrenia is rooted in an abnormal dopamine system examine human subjects who have not taken neuroleptic medications. A study in 1982 emphasized that almost all of the subjects with schizophrenia in the postmortem studies exhibiting abnormal levels of dopamine had taken neuroleptics prior to death, and that ‘schizophrenic’ subjects who did not receive any neuroleptic drugs had normal levels of dopamine (Read et al., 2004, 61). It was assumed that “these findings do not support the presence of elevated DA [dopamine] turnover in the brains of the schizophrenics” (Read et al., 2004, 61). A subsequent study claimed that “no consistent differences between drug-free schizophrenics and normals have been found in terms of dopamine levels” (Read et al., 2004, 61). A different method of verifying the dopamine hypothesis is to determine the quantity of dopamine metabolite (HVA) in the spinal fluid. However, this is an uncertain and weak method but does enable the involvement of existing subjects and in so doing facilitates the inhibition of neuroleptics for certain duration of time before looking at the fluid (Siegel & Brady, 2011, 292). As expected, no differences were identified. On the other hand, another method places emphasis not on dopamine quantities but on the dopamine receptors. Elevated levels or reinforced sensitivity of dopamine receptors would substantiate the dopamine hypothesis. Four studies, by 1982, had identified differences, but one study discovered none (Grace, 2010). Still, it had also been found out that neuroleptic medications stimulate hyper-sensitivity in dopamine receptors. Haracz, having emphasized that the four controversial studies “included only a small number of patients who were drug-free for one month or more before death” (Yatham & Maj, 2011, 125), assumed that further research is required to prove whether the findings of the four studies were “secondary to a drug effect or to the schizophrenic disease process” (Yatham & Maj, 2011, 125). Numerous current studies have looked for differences in the different forms of dopamine receptors and have used advanced technologies in neuroimaging, like ‘single photon emission computerized tomography’ (SPECT) and ‘positive emission tomography’ (PET) (Read et al., 2004, 61-62). Currently, four evaluations of the studies on the dopamine hypothesis presented an assessment of the extent of the growth of the field after a century of brain research with an increasingly advanced technology. A particular evaluation recognizes that “few studies have provided convincing evidence of altered dopaminergic activity” (Weinberger & Harrison, 2011, 2034). Another evaluation reports: “While postmortem and imaging studies have identified numerous alterations in brain structure and function in schizophrenia, the fundamental nature of the pathological process associated with this illness remains poorly understood” (Read et al., 2004, 62). Even so, the dopamine hypothesis is still strong and widely recognized. In the absence of it, it would be impossible to validate the importance of the drugs. Yet, without the drugs there could be no disparities to justify the hypothesis. As a component of the current ‘neurodevelopmental theory of schizophrenia’ introduced by Daniel Weinberger, a ‘modified’ form of the dopamine theory has been presented. The ‘modified’ dopamine hypothesis aims to explain cognitive disorder and negative symptoms, acute aspects of schizophrenia that the original hypothesis failed to explain. In the modified version, schizophrenia is linked to, but not automatically rooted in, a dopamine dysfunction relating to a surplus production of dopamine in the brain’s subcortical systems and a low quantity of dopamine in the prefrontal cortex (Noll, 2007, 137-138). Dopamine processes in the subcortical system could be overactive, abnormally triggering D- 2 receptors and generating delusions and hallucinations. Dopamine processes in the prefrontal cortex could be ‘hypoactive’, leading to the excessive activation of D-1 receptors, cognitive disorders, and negative symptoms (Noll, 2007, 137-138). Both the original and modified dopamine hypothesis has inadequate empirical proof. Up to now, there remains no credible finding that shows dysfunctions of the dopamine system in schizophrenia. Postmortem neuropathological research has been unconvincing and questionable. Although the over-activity of subcortical functioning at D-2 receptors has been substantiated, other components of the modified dopamine theory have remained uncorroborated. Hypotheses about dopamine abnormality and the development of cognitive disorder and negative symptoms, and the theory that positive symptoms become separate from the dopaminergic process and self-sufficient in treatment-resistant, chronic schizophrenia, are unsubstantiated with reliable proof (Howes & Kapur, 2009, 555). The modified dopamine theory, similar to its antecedent, will perhaps have a brief existence in the field of science. In truth, as any mental health professional can assert, there is hard proof disclaiming the original and modified dopamine theory: antipsychotic medications do not consistently eliminate delusions and hallucinations. Support for this clinical finding is presented in studies that, in several individuals, delusions and hallucinations develop when, actually, there appears to be evidently normal quantities of synaptic dopamine (Bennett, 2009, 718). Restricting these individuals D-2 receptors with antipsychotic medications has insignificant or no impact on their mental disorder. As stated by Stone and colleagues (2007), this could imply that other neurotransmitter networks working separately from dopaminergic mechanism could also generate positive symptoms. Even though disproved as a causal theory, the dopamine hypothesis of schizophrenia remains widely recognized in the pharmaceutical industry. The theory that certain neurotransmitter receptors can be activated or blocked by certain drugs, and that symptoms of mental disorder would diminish from this process, has until lately drove the pharmacological field and industry to adhere to dopamine hypothesis for schizophrenia and other single-transmitter theories of mental disorder (Boot et al., 2011). Such exact and specific theory is appealing not only to researchers, but as well as to those promoting new treatments (Noll, 2007, 138): single-transmitter medications can be easily understood by people who are generally science-naive. In truth, there are more or less a hundred of neurotransmitter networks discovered in the brain, and if a certain network is modified by drugs, it remains unclear how this impinges on other neurotransmitter networks (Noll. 2007, 138). More recent groups of psychoactive drugs affect several receptors of at least two neurotransmitters, and the impact on the other parts of the brain could be also more difficult to determine (Kruzich et al., 2006). Nevertheless, even though an abnormality in the production of dopamine is no longer believed as the only source of schizophrenia, it is certain that dopamine contributes to the pathophysiology of positive set of symptoms (e.g. delusions, hallucinations, etc). Conclusions In conclusion, it is probable that the dysfunction of the dopaminergic system is rooted in other disorders somewhere else in the brain. The dopamine hypothesis of schizophrenia is corroborated mostly by the findings that antipsychotic drugs work by restricting the D-2 receptor. Nevertheless, due to the discovery of the ‘new’ antipsychotic medications researchers have finally understood that multiple receptors are involved in schizophrenia. Therefore, one of the major weaknesses of the dopamine theory is the fact that it is not founded on identifiable physiological changes in dopaminergic activity. Still, whether dopamine is connected to the development of schizophrenia remains inconclusive. This issue is much more difficult to resolve due to the fact that schizophrenia is classified as a neuro-developmental illness. Further research is thus required. References Bennett, M. (2009). “Positive and Negative Symptoms in Schizophrenia: The NMDA Receptor Hypofunction Hypothesis, Neuregulin/ ErbB4 and Synapse Regression”. Australian and New Zealand Journal of Psychiatry, 43(8), 711-721. Boot, E. et al. (2011). “Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia—relationship with COMT Val Met polymorphism, gender, and symptomatology”. Journal of Psychopharmacology, 25(7), 888-895. Grace, A. 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