Explaining Biological Depression Theories

I am grateful to Dien Ho and James Phillips for their comments on my article (Mulinari, 2018). Although they approach the topic from different perspectives, they both seem to find my account of the evolution of monoamine theories into neuroplasticity theories to be compelling. They especially seem to find my principal argument to be persuasive: Until quite recently, the use of drugs to generate and test pathophysiological hypotheses—the pharmacological bridge—has been a paramount driving force in psychiatric research.

In his thoughtful commentary, Phillips is right to draw attention to the role of "nonbiological" factors, which tend to be overlooked by biological psychiatry, in the etiology of depression. He suggests that concepts from neuroplasticity research may provide an opportunity to link the nonbiological and biological levels. Specifically, he suggests that via epigenetic mechanisms, "developmental and environmental etiological factors may elude the pharmacological bridge but still be connected to neuropathophysiology." Indeed, this is the position held by proponents of neuroplasticity theories, as described in my article. These researchers posit that environmental exposure interacts with individual genetic constitution to determine risk for depression throughout life and use various animal stress models to test this thesis.

By contrast, the earlier theories that I reviewed did not explicitly incorporate social or environmental triggers, but this omission was not necessarily due to a lack of conviction among researchers and clinicians concerning the relevance of nonbiological factors. In fact, in his original catecholamine hypothesis paper, Schildkraut (1965, p. 517) emphasized "the significant effects which social and interpersonal factors have on the clinical response to antidepressant drugs," even though he excluded them from his theory.

This quote suggests that the disregard for nonbiological factors was not due to genuine commitment to biological reductionism. Instead, such neglect at this point may stem from various sociological factors, such as disciplinary and professional interests and constraints (Mulinari, 2012), as well as from the availability of particular technologies (e.g., drugs) that seemed useful for advancing research (and researchers).

Yet the more recent incorporation of social and environmental factors into biological research and theories may pose its own problems. Current theories of depression conceptualize social and environmental factors as external stressors, but this arguably represents too narrow an understanding of the (human) social environment (Choudhury et al., 2009). Again, however, this conceptualization may possibly be contingent on the availability and convenience of specific technological configurations (e.g., animal stress models), rather than reflecting a philosophical commitment among neuroscientists.

Toward the end of his piece, Phillips seems to suggest that ultimately the "social" and "biological" realms might be fundamentally separate and that consequently, studies of the "social" and "biological" may be incommensurable. Although fascinating, this enduring issue is beyond the scope of my paper. Nevertheless, Phillips's suggestion of incommensurability between social and biological ontologies and epistemologies does point to what I described as the "hard core" principles of a mainstream biological psychiatric research program: 1) distinct psychiatric disorders reflect distinct alterations in brain function, and 2) effective psychotropic drugs counteract these alterations. A particularly clear explanation of this "hard core" was provided by Nancy Andreasen (1984), a prominent psychiatrist with close ties to the DSM III task force responsible for drafting the manual, when a few years after its launch she wrote:

The major psychiatric illnesses are diseases… caused principally by biological factors, and most of those factors reside in the brain…As a scientific discipline, psychiatry seeks to identify the biological factors that cause mental illness… This model assumes that each different type of illness has a different specific cause…Because these diseases are considered to be of biological origin, the therapy is seen as correcting an underlying biological imbalance.

(pp. 29–30; emphasis in original)

This quote from Andreasen, and the discussion regarding the "hard-core" principles of biological psychiatry, brings me to Dien Ho's commentary. I am greatly indebted to Ho for contextualizing Lakatos's theory of research programs and for highlighting some limitations in his theory, as well as in my particular use of Lakatosian concepts. In the paper, I argued, despite the many wellrecognized problems, that "research programs" could still be of significant heuristic...