From Chaos to Consilience

What does mind–body neurobiology contribute to the diagnosis of depression?

As with the various classification strategies for cancers in Tumor Town, our current diagnostic schemas do not “cleave nature at the joints.”^9,10 Said another way, given the current state of our brain–body science, conditions such as major depression are better thought of as smaller pieces of larger and more physiologically coherent wholes, not as discrete disease states. This idea is not new to this article, of course, but has been articulated many times in concepts such as “affective spectrum disorder,”¹¹ which marries mood disorders to an array of other frequently comorbid conditions (eg, chronic pain and fatigue, attention deficit disorder, posttraumatic stress disorder, and social anxiety disorder).

But these discussions frequently give short shrift to 3 key implications of recent scientific findings. The first implication is that swapping a smaller rigid diagnostic category for a larger rigid one misses the important truth that all conditions such as major depression are probabilistic in their presentation and very likely probabilistic in their underlying pathophysiology as well.¹² They are not the hard–and–fast certainties that DSM diagnoses have become over the years but rather like Darwinian species that blend into each other at the edges and show significant variations between individuals in the same groups. From this perspective, asking where major depression ends and anxiety begins is biologically meaningless. They fade into each other at their edges and coexist in each other’s centers.

The second implication is that grouping of conditions such as major depression, anxiety disorders, and states of pain and fatigue into a larger whole doesn’t just parsimoniously account for high rates of comorbidity between these syndromes and symptoms.^13,14 Rather, viewing these conditions as components of a larger whole more accurately reflects the astounding similarities that have been uncovered between these syndromes in terms of shared genetic and environmental risk factors, as well as underlying brain and body pathophysiology.⁵ Indeed, the fact that no 2 depressions look exactly alike or that depression bleeds into many other diagnoses is no accident but rather reflects the neurobiology of depression itself.

The key point here is that there is no simple land bridge between specific genes and specific symptoms or syndromes. Lying between these twin shores on which psychiatry has staked its reputation is a churning sea of widely disbursed, highly complex, interactive brain–body danger/adaptation pathways that must be comprehended if we are to understand why depression is the way it is.¹⁵

A final implication of the new science—which we will return to at some length in the third part of this series—is that specific symptoms are more real and more therapeutically meaningful than the syndromes to which they contribute. Rather than focusing on disease states when we treat mood disturbances, the new science tells us that we would do better to focus on the specific symptoms that any given patient actually has. As a direct result of the neurobiology of depression, all diagnostic categories are part myth and part probability. While these categories simplify our communication with each other, and can aid scientific research when not taken as delivered directly from the hand of God, they are not as real as the unique combination of symptoms that each individual patient has at any given time. It is these symptoms (not the categories they form) that must be resolved if a person is to gain the benefits of remission. Each symptom that a patient has is a marker that his or her underlying physiology remains in a state known to produce long–term emotional, functional, and physical damage.⁵

Is our view of major depression too big or too small?

As is often the case with these types of questions in psychiatry, the answer is “Yes!” And here our analogy to Tumor Town breaks down, as all analogies eventually do. Tumor Town is a good way of thinking about ways in which our view of depression is too small and too rigid. Our current views are too small because major depression is only one probabilistic syndromic manifestation of underlying patterns of mind–body dysregulation that also give rise to many closely related diagnoses.

What Tumor Town doesn’t capture is the fact that what we currently call major depression—while associated with typical abnormalities at the level of brain–body function—is almost certainly not a single disease process. (Here we are assuming that disease means a condition with a specific biological cause(s) that, when corrected, leads to disease eradication. In this regard, the old disease of dropsy is a better analogy for major depression than is Tumor Town. Before we understood transudative and exudative processes in the lung, before we understood that pulmonary edema could be caused by failures in very different organ systems (ie, heart versus lung), we had dropsy—a single condition that accounted for all cases of “water on the lung.”