- Dopamine and Discovery
schizophrenia, scientific discovery, theory change, dopamine hypothesis
Kendler and Schaffner have written an exemplary case study of the rise of the dopamine hypothesis and, if not its fall, at least its stagnation and transmutation. They bring out well both the state of the science and the opportunities offered by the theory to consider some famous philosophical theories of scientific progress. So well, in fact, have they done this, that I do not have a lot to say about it. I will just mention one or two points that I found interesting, and then say a little about what looks to me like an omission from the story that the two Kens recount.
One point they raise is the importance of competitor theories: now, there is supposed to be an old story about a quack who was apprehended during the Lisbon earthquake selling pills: "Pills to stop the earthquake." When outraged bystanders pointed out that you cannot stop an earthquake with pills, he said "I know, but what's your alternative?" It is natural, I think, to feel that a moribund theory, prone to ad hoc modification, should be jettisoned. But it is also natural to think that a theory with even a modicum of empirical support in its neighborhood should be retained and investigated further if there is no apparent alternative: even if you only have ten dollars in the bank, you would not burn it because someone is promising to make you rich at some unspecified point in the future if you do so. The issue they raise is where competitors might come from, and especially how we are to evaluate what look like competing hypotheses generated within the original research program.
One moral of the story here is that as a research program—or what Kendler and Schaffner call a temporally extended theory—changes over time, its core commitments seem to change, too, but somehow not from the point of view of the scientists who are intellectually and materially invested in it. As they note, in some of the cases Kendler and Schaffner describe we have, in fact, substantially different competitor or replacement theories that are advertised as mere variations on the existing dopamine theory. They stress the passage they quote from Carlsson and Lecrubier (2004, 99) in which a theory is presented as a 'new lease of life' for the dopamine hypothesis, even though it substitutes dopamine dysregulation for dopamine hyperactivity and relegates even that to a subsidiary role in a model which sees information-processing deficits in prefrontal cortex as the primary deficit.
Lisman et al. (2008), in a speculative paper rather than a review article, argue that schizophrenia depends on interactions between numerous neurotransmitters—glutamate, GABA, dopamine, and acetylcholine are all mentioned—as well as between those neurostransmitters and numerous genes. They sketch a circuit-based approach in [End Page 69] which a malfunctioning feedback loop between pyramidal cells and fast-spiking interneurons affects the dopamine system, causing a positive feedback loop between hippocampus and Ventral Tegmental Area (VTA) that generates psychosis. They argue for this in part based on recent work on glutamate as well as the familiar findings about dopamine pharmacology that Kendler and Schaffner cite.
This is another example in which dopamine is relegated to a downstream causal role, but the dopamine hypothesis still seems to be going strong—at least in terms of appeals to longstanding belief about its centrality. The original evidence for the dopamine hypothesis, which seems to have led nowhere, is still being appealed to by Lisman et al. In general, it seems that any dopamine abnormality at all will end up being cited as evidence that the dopamine hypothesis was right all along; the problem is that just about everything seems to be abnormal in the brains of schizophrenics, so the theory, in that most general form, is pretty much bound to be true.
Scientists are not often intellectually conservative. Some are notorious for claiming that they have come up with some radical new idea when all they have really done is to rearrange things. Yet here is a manifesto for a replacement of a core commitment of psychiatry, and...