The Dopamine Hypothesis of Schizophrenia: An Historical and ...

More documents

Recommendations

Info

Kendler and Schaffner / Dopamine Hypothesis of Schizophrenia ■ 53 Figure 2. Schematic of the revised DHS proposed by Davis et al (1991). DHS – dysregulation of DA in brain Down regulated Mesocortical DA System Up regulated Mesolimbic DA System Due to increased turnover Due to increased postsynaptic receptor function Due to increased turnover Due to increased postsynaptic receptor function tive theoretical approach toward the etiology of schizophrenia have been possible? and (ii) Why has the DHS persisted despite its relatively poor empirical track record? Evaluation of the DHS in the Light of Four Theories About the Nature of the Scientific Progress Karl Popper In their influential review, Meltzer and Stahl (1976) wrote If, as Karl Popper says, the value of a hypothesis lies not so much in whether it is right or wrong but in its capacity to stimulate attempts to refute it, then the DA hypothesis of schizophrenia has been extraordinarily successful. A PubMed search for “schizophrenia” or “psychosis” and “dopamine” yielded 5,880 articles from 1963 to March 2008. If the criterion for success of a theory is its ability to generate research, then Meltzer and Stahl are correct and DHS has been strikingly successful. However, Popper’s work on the evaluation of scientific theory repeatedly stressed not the generativity of a theory but its falsifiability (Magee 1982). Only by examining how a theory could be disproven was it possible, according to Popper, to discriminate a truly scientific from and a pseudo-scientific theory (Popper 1959, 1962). Furthermore, according to Popper, theories could vary in their degree of falsifiability. Theories of greater falsifiability are, Popper argued, of greater scientific value because they make bolder and more informative claims. Scientific progress would consist of a series of conjectures
54 ■ PPP / Vol. 18, No. 1 / March 2011 and refutations, as newer and yet more falsifiable theories were advanced. How would the DHS fare on these Popperean grounds? At its inception, the DHS was highly abstract and nonspecific, postulating that the etiology of a complex neuropsychiatric syndrome was due to hyperactivity in one neurotransmitter system. Even at the time of the articulation of the DHS, neurotransmitter systems were known to be complex and diverse, with the same neurotransmitter being used in different pathways with distinct functional roles. Control mechanisms existed at many levels, both within and between cells. Overactivity of the system could arise in many ways. As scientific understanding of brain functioning advanced, this problem became worse, making it more and more difficult to articulate a single, clear test of the DHS. Because of the complexity of the systems involved, the DHS was elastic in absorbing a wide range of results. The IT version of the DHS predicted that levels of DA and HVA should be increased in the brains of individuals with schizophrenia. However, the IRF version of the DHS could produce a decrease in DA and HVA levels. If abnormalities were not found in global measures of DA function, then it was because the abnormalities in schizophrenia were found only in specific brain regions or pathways. In Popper’s terms, the DHS had a low degree of falsifiability. As Popper might have predicted, given its abstract formulation, if one prediction of the DHS was not confirmed, another easily took its place. This nonspecificity allowed the DHS to take on the protean features that we described. In this process, the DHS has become nearly immune from falsification. Indeed, in its latest incarnation (see quote above), it seems to be more of a general framework than a specific theory. There is a deep irony in the observation that the DHS has fared poorly at the Popperean criterion of falsifiability. The DHS emerged at a time when the nascent field of biological psychiatry argued strongly that psychoanalysis had to be abandoned. One key argument was that psychoanalysis was not a science that was illustrated by the protean and non-falsifiable nature of key psychoanalytic theories. Such theories, they argued, could explain anything. At its inception, early biological psychiatrists would have insisted that the DHS was the antithesis of psychoanalytic theory. However, over time, the nature of DHS as a scientific hypothesis has come to resemble the psychodynamic theories that it was meant to displace. Scientists have frequently embraced the Popperean philosophy and, on deeper reflection, later became more critical of this approach (Katz 1994), in part because the actual flexibility and practice of science go beyond the Popperean model. It is to such alternative approaches we now turn. Thomas Kuhn The work of Kuhn in his classic “The Structure of Scientific Revolutions” (Kuhn 1996) can help us to understand the endurance of the DHS. For Kuhn, Popperean falsification did not accord with scientific practice. Rather, Kuhn suggested that scientists work within broad conceptual frameworks or “paradigms.” Like most human beings, working scientists find it difficult to think outside the framework in which they “grew up.” Indeed, Kuhn suggested that scientists typically strongly resist purported falsifications of their paradigms, and irrationally retain belief in them in the face of increasing anomalies. However, at some critical point, two things can occur together, which unleashes what he termed a “scientific revolution.” First, the accumulation of anomalies in a particular research paradigm becomes unsustainable. Second, another paradigm becomes available that does a superior job at explaining these anomalies. Then the scientific field undergoes a crisis, and experiences a “conversion” as individual researchers (more often the young than the old) switch to the new paradigm. The DHS probably does not rise to the level of a Kuhnian paradigm, which might, for example, be an appropriate description for the “biomedical model” for psychiatric disorders. Nonetheless, some of the insights of Kuhn on the historical process of science can be usefully applied to the DHS. In particular, no revolution has occurred in theories about the etiology of schizophrenia that has resulted in the wholesale abandonment of the DHS. Why? Certainly, many empirical findings, some outlined above, are poorly explained by the DHS. However, one key ingredient has been
Page 1 and 2: The Dopamine Hypothesis of Schizoph
Page 3 and 4: 42 ■ PPP / Vol. 18, No. 1 / March
Page 13: 52 ■ PPP / Vol. 18, No. 1 / March

The Dopamine Hypothesis of Schizophrenia: An Historical and ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?