Emotional pain without context

MRI coronal view of the hippocampus
MRI coronal view of the hippocampus (Photo credit: Wikipedia)

Siddhartha Mukherjee provides a brief history of the serotonin hypothesis of depression, its demise and why dismissing serotonin may be an “overcorrection.”

Part of this story is an emerging theory of depression:

A remarkable and novel theory for depression emerges from these studies. Perhaps some forms of depression occur when a stimulus — genetics, environment or stress — causes the death of nerve cells in the hippocampus. In the nondepressed brain, circuits of nerve cells in the hippocampus may send signals to the subcallosal cingulate to regulate mood. The cingulate then integrates these signals and relays them to the more conscious parts of the brain, thereby allowing us to register our own moods or act on them. In the depressed brain, nerve death in the hippocampus disrupts these signals — with some turned off and others turned on — and they are ultimately registered consciously as grief and anxiety. “Depression is emotional pain without context,” Mayberg said. In a nondepressed brain, she said, “you need the hippocampus to help put a situation with an emotional component into context” — to tell our conscious brain, for instance, that the loss of love should be experienced as sorrow or the loss of a job as anxiety. But when the hippocampus malfunctions, perhaps emotional pain can be generated and amplified out of context — like Wurtzel’s computer program of negativity that keeps running without provocation. The “flaw in love” then becomes autonomous and self-fulfilling.

He proposes an alternative understanding of the role serotonin may play:

An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire. Rather, it appears to change the wiring itself. Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits.

This still doesn’t explain the variation in responses to psychotropics. He acknowledges as much and alludes to the need for new typologies of depression. (Remember the dark ages when we talked about endogenous vs. exogenous depressions?)

The layers of speculation can obscure or illuminate just how crude our understandings of depression and the brain are. This, along with the history of psychiatric fads and abuses, makes one wonder if we should proceed a little more cautiously and work a little harder to capitalize on non-pharmacological tools like exercise and social support.

9 thoughts on “Emotional pain without context

  1. Very informative blog and effective news on Hippocampus. When I look into addiction, something this brain organ is responsible. I have read so many books and wrote content specifically on brain and psychology. Dentedego.com is such a place that spreads content on multiple subject maters.

  2. Interesting–we seem to have taken away different messages from Mukherjee’s article. Your take: this is more evidence that we should be putting the brakes on drug use when it comes to depression. My take: We threw the baby out with the bathwater, and the serotonin hypothesis of “chemical imbalance” as a cause of depression is alive and well and becoming more sophisticated and robust. Better medications that will take advantage of the revivified serotonin hypothesis are in the offing.

    1. Dirk,

      Thanks for sharing your thoughts.

      I’m open to his suggestion that we may be in the middle of an over-correction and I’m hopeful that a better understanding of the problem and treatments will emerge from this.

      I look at this history and see a lot of wasted money, time and cultural capital. If building understandings of these complex problems is an iterative process, we hung on to this iteration for too long, over-sold it and failed to recognize that these medications are not very helpful for most and harmful for some.

      My closing thoughts were meant to suggest that we learn from these mistakes as the next iteration emerges.

      All the best,


      1. We basically agree, then. But we do need to balance the “wasted money, time and cultural capital” against the uncounted lives saved when many people suffering from Major Depressive Disorder found a medicine that worked for them. It’s hardly their fault that, for various reasons, people who had no business taking these pills ended up on the medications anyway.

      2. I agree, it’s absolutely not the patient’s fault and it’s a very good thing that people who have benefited from those drugs have had access to them.

        I’m reading the book Crucial Confrontations and just something that seems germane and also indicates that this problem is not limited to depression treatments:

        “Last year 41 million colds were erroneously treated with antibiotics because doctors were unwilling to confront patients who demanded drugs. Patients show up with a cold, don’t like to be told that their illness will just have to run its course, demand antibiotics, and get them—even though they won’t help. Why? Because the doctors can’t “just say no” to drugs.”

        Doctors haven’t been asking the questions they should ask and “owning” the treatment they provide.

        Drug companies have been muddying the pool of information for prescribers and patients and they have been marketing directly to patients.

        You often hear depression referred to as the common cold of mental illnesses. Maybe that expression fits in more ways than one! (Recognizing the colds can progress into pneumonia and be a more serious threat to people with other health problems.)

        Between the explosive growth in medical spending and the looming implementation of the Affordable Care Act, I’m increasingly concerned about maximalist medical care across the board. Whether it’s C-sections, CT scans or statins.

        It’s tough to balance these


        All the best,


  3. Please help I cry and can’t stop I support my family and can’t crumble but I’m gone I hate the pain and can’t get escape I’m in need of relief and am thinking of resorting to drug abuse. I can’t do this and survive.

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