Further Thoughts on the Dopamine Hypothesis of Schizophrenia

We are gratified at the largely positive comments on our essay on the dopamine hypothesis of schizophrenia (DHS) by these two distinguished commentators from the fields of biological psychiatry (Dr. Tamminga) and the philosophy of psychiatry (Dr. Murphy). There is little that they have said with which we disagree. Rather, we want to expand briefly on their commentaries.

We found Dr. Tamminga's reactions to be particularly fascinating because she has been an "insider" to the story of the DHS as it has unfolded. She provides substantial insight into the "extra-scientific" reasons for the persistence of the DHS despite its poor empirical record.

She validates our impression that the DHS was in its first years of existence closely intertwined with the identity and pride of the then new biological psychiatry movement. She reemphasizes our concept of biological psychiatry as a young science with excess avidity for its hypotheses that extend beyond their empirical base. The rest of medicine and neurology were developing pathophysiological theories. She writes "How could we say that we had no idea at all about the disease pathophysiology of something so florid as schizophrenia? Having the DHS supplied a need to know" (2011, 66). At this time in the history of psychiatry, the threshold for proposing a model of disease etiology was low. Enthusiasm was high and the bare outlines of a theory were adequate. She comments with poignancy how terribly simple the DHS now looks given the subsequent developments in neuroscience.

In a further elaboration of that simplicity, Tamminga suggests that the DHS "was never exactly a hypothesis—it was more like an Idea. Because we had not previously had such specific hypotheses to explain our illnesses, our criteria for developing one were weak and fluid; perhaps our excitement about the idea led us to label it 'hypothesis' much too quickly. Today, we might call this a speculation" (2011, 65). We attempted to capture this notion of a simple and fluid idea in our notion of a "high-level central hypothesis," to be distinguished from more specific, lower-level hypotheses that amplify the central hypothesis. It is the high-level central hypothesis that typically differentiates a theory from competitive theories that contain contradictory, high-level central hypotheses, and provide an ongoing "temporally extended theory" (our term) or "research program" (to use Lakatosian terminology) with its long-term identity (as also noted by Murphy in his commentary).

Why did the DHS persist? Tamminga sensibly suggests that the longevity of the DHS can in part be explained by the absence of a clear competitor with superior or even equal empirical support. She also emphasizes what might be described as emotional factors when she writes

I wonder to myself why we were so resistant to "facing facts," so blind. Of course, it deserves being said that for many years, the Dopamine Hypothesis represented every shred of neurobiological knowledge that we possessed about schizophrenia; it organized our approach to the illness.

(2011, 65)

The DHS was central to the field of biological psychiatry. Objectivity was, we suggest, sacrificed by the strength of this attachment. One of us (KSK) has had the experience of presenting, before a psychiatric audience, parts of our paper that are critical of the underlying validity of the DHS. Several members of the audience reacted with vigor, literally rising out of their seats in anger. It was as if the dignity of their mother was under attack.

We enjoyed her retrospective thoughts. Looking back now, she writes

A perspective from current neuroscience discovery might suggest that posing hypotheses before knowledge (especially the paradigm-shifting discoveries in neuroscience of the late twentieth and early twenty-first centuries) would generate only superficial, incomplete, and weakly supported concepts.

(2011, 66)

We pondered her final discussion about whether the DHS "perverted advances" or not? She seems to argue that it did not, suggesting that we were simply too ignorant in those days to formulate any theory that had the possibility of being correct (except by chance). We wish she had outlined her line of...