An expanded neurobiology of depression?

Jeff Oristaglio is a neuroscientist at Drexel University with whom I share an interest in better understanding the brain and its relation to human experience generally.  The continuing conversation here is excerpted from an ongoing email exchange between Jeff and me, and made available to encourage further thinking about possible future directions for productive research on the neurobiology of depression.  Others interested are invited to add their thoughts in the on-line forum below. 

PG - 11 June 2009

Meeting announcement: "To think more about what depression is."

Jeff - 11 June 2009

Just curious- what, precisely, is the question regarding 'what depression is'?

Paul - 11 June 2009

That's a seriously interesting question. My hunch is that there is a way to make sense of depression other than the generally understood ways (sadness, lack of interest/motivation, chemical imbalance), that there is a richer "story" of what is going on in terms of interactions between unconscious and story telling brain functions. See, for example, /exchange/node/2175 and /exchange/mentalhealth/fromtheinside/depression. So, "what depression is?" means let's drop some of our explanatory presumptions and see whether there are new things to learn by looking more carefully at descriptions people provide of their own experiences. 

Jeff - 11 June 2009

If I read you correctly, you're interested in the different ways depression manifests itself across individual psyches, and, presumably, what you can learn about other people (or introspectively from yourself) by examining idiosyncratic responses to the illness.

To me, that's a much different question than 'what is depression'? What you have, in essence, is a psychiatry forum- minus the heavy focus on treatment strategy.

Paul- 12 June 2009

Do I detect a note of dismissal in "a psychiatry forum - minus the heavy focus on treatment strategy"? And a sense that "depression" is already understood, with only the problems of "idiosyncratic responses," variations in the way it "manifests itself across individual psyches" left to be explored? From my perspective (as both neurobiologist and experiencer), depression is very far from "understood" and the most likely path to better understanding (for both neurobiological and therapeutic purposes) is to take a closer look both at variations AND commonalities across the experiences of individuals.

Jeff - 14 June 2009

Not being dismissive. Like you, I understand all too well significance of 'idiosyncratic responses.'  However that's a separate issue from depression as a disease. In latter case, I don't agree with 'very far' from understood. I think we understand it pretty well. Details still to fill in, of course, but the pieces are coming together.

No different than the consciousness issue, or the evolution of life for that matter. I think you'll agree that the fact we cannot definitively explain, beyond any doubt, why dinosaurs went extinct doesn't mean we don't understand natural selection, and the role contingency plays in the process.

Likewise, there is a neurobiological explanation of consciousness. But understanding it will not give you access to another's subjective experience, nor will it explain why their experience has the particular quality it does. But given a scientific explanation, all of these things can be understood 'in principle' (i.e., complete access to person's life experiences, etc.).

Conway's 'Life' comes to mind here, no? The rules are simple, but understanding how something like a glider comes around (or some of the bistable patterns) pretty hard to fathom without tracing the history step-by-step. Does this mean we don't understand the game? Depends what your criterion is I guess. But be careful here. If you equate 'understanding depression' as comparable to predicting gliders given only basic rules, your whole effort may be doomed to failure.

To me, knowing the underlying rules (or causes- physiological, psychological, environmental,...) and being able to look at, listen to, depressives and say realistically, "yeah, I can see how you might have felt that way, given the fact that your cortisol was spiking, the messy divorce, your compulsive, pessimistic disposition, ..." IS understanding, as best we can get it- ever, I think. From my perspective, factoring out the commonalities not only best way to understand, but IS what constitutes understanding. But I would argue that we're very far along on this road.

PG - 24 June 2009

Lots of interesting stuff here.  Yes, emergent systems relevant.  And yes, is likely that any particular depression is not only "pretty hard" to predict "without tracing the history step-by-step" but literally impossible to predict otherwise.  And yes, there is additionally a "contingency" factor.  So "understanding" depression certainly does not mean to either of us having a detailed mechanistic explanation of any given case.  Many of the idiosyncracies of given cases  are indeed ... idiosyncracies, of considerable interest in better understanding individual lives but of less interest in understanding depression as a general phenomenon.

The remaining issue is whether our current knowledge of the "underlying rules" is understanding "as best we can get it - ever."  And my hunch is that the answer is no, that there is more involved than pharmacological status, life experiences, relatively stable "personality characteristics" and the interaction among those.  No, I am not suggesting that there is something more than neurons and their interactions but yes, I suspect there are features of the higher order organization of neurons that need to be included among the "underlying rules" to achieve a better understanding of depression, both conceptually and for therapeutic purposes.  And my bet is that we can get a better handle on those by paying more attention to peoples' accounts of their internal experiences with depression, by not dismissing these as wholely idiosyncratic but rather taking them as "data" and looking for commonalities among them.

All this is, again, a hunch, and the proof of course is in whether one actually finds such commonalities and whether they in turn point to relevant but underappreciated features of nervous system organization.  The jury is, of course, still out on that, but my sense is that the answer to both questions is turning out to be yes (cf /exchange/mentalhealth/workinggroups09/june15#comment-106526; your initial question and our exchange was an important background to the conversation from which this came). There are indeed common features to peoples' accounts of their internal experiences with depression, and they in turn suggest that internal experiences are not only not completely idiosyncratic but that internal experiences are not simply epiphenomena either. Internal experiences (what I call "stories") increasingly seem to me to be one component of a web of reciprocally interacting nervous system components out of which depression emerges.  On this account, internal experiences are not only useful data for better understanding depression but as causally significant in it as are pharmacological status, life experiences, and "personality."  And offer as much of a target for therapy as any of the other interacting elements.

A "less wrong" neurobiology of depression?  What do you think?