Neuroscientists Report Depression Cause: Stress, Even Traumatic Stress

Karen Wager-Smith, PhD and Athina Markou, PhD of UCSD conducted a thorough review of the literature. It was published in Neuroscience and Biobehavioral Reviews 35 (2011) 742-764.  They report evidence that stress, including traumatic stress is an unrecognized cause of depression.  Dr. Wager-Smith is a neuroscientist who contacted me to ask if I could help advertise this to the public.  I am happy to do so, through this article and interview with Dr. Wager-Smith.

DT:     Can you please let us know what initially inspired you and your colleague to look into this issue so deeply?

Dr. Wager-Smith:  In the biomedical field, our model for what causes psychiatric problems was that certain individuals carry some sort of pre-existing vulnerability, which causes some aspect of brain biology to eventually malfunction, it is this malfunction that causes depression, and that drugs are required to correct this problem.

Stress was thought to be a nonspecific factor that can hasten the detonation of this hidden time bomb.

But as Athina and I were studying animal models of depression, we kept finding hints that this whole premise was wrong. It started when we found that in our experiments, stress was inducing a tissue repair response in the brain. This was a very unexpected finding for us. Why was stress inducing a brain repair mechanism? I looked through the biomedical literature to try to find answers.

To my surprise, I found overwhelming evidence within the published biomedical literature that stressful events cause microinjuries and remodeling in the brain, that the brain’s inflammatory system is activated in this situation to repair the damage, and that the molecules released during this response can cause depressive symptoms in people and animals because these symptoms promote convalescence.

Furthermore, different types of stressors seem to injure and remodel different parts of the brain, and this neuronal plasticity is accompanied by development of different long term behavioral solutions that cope with the stressor.  After reading all the literature, we had the impression that what we were observing as an injury-repair cycle was actually concerted neuronal remodeling process that enables the individual to adapt psychologically to the unique stressful event.

It’s very similar to the way bone is shaped by experience. Unusual or repeated physical stresses cause the bone to develop microfractures in weak areas. These microfractures are repaired in a way that bolsters the strength of the bone in that area. In this way the bone is continuously remodeled in accord with the demands placed on the working tissue. The deeper I looked into the issue, the more data supported that idea for depression.

DT:  What are the implications of your literature review for depression sufferers?

Dr. Wager-Smith:  Like others in my field, before I began this research, I assumed that depression was a biological malfunction and the solution was medication that influences neurochemistry. After doing this research, I now think the data more strongly supports an alternative idea. Depression is a natural convalescent period that occurs while a neurobiological plasticity process is accomplishing a major revision of an individual’s psychology and behavior that is necessary to properly adjust to life events or situations.  So I think the most important implication for depression sufferers is to consider supporting their depression as a healing response to a damaging life circumstance, rather than attacking their depression as a brain malfunction. Now this is not to say that this natural healing process doesn’t occasionally go awry and become pathological.

DT:  What do you think is an urgent need for these people?  For the therapists who treat them?

Dr. Wager-Smith:  If you had an injury elsewhere in your body, you wouldn’t expect a drug to heal it. You would use splints, sutures or casts to help support proper healing, and these interventions would reduce the risk of ending up with chronic pain and disability. You would accept that the injured body part is going to be out of order for a period of time, and that concerted rehabilitating exercises might be necessary after healing has completed in order to regain full strength and flexibility.

I think it would be fruitful to apply these same therapeutic concepts in depression. A good therapist may function as a psychological cast to guide the client through the process of recovery from the stressful life event that triggered the depression. I think a period of incapacitation should be expected during healing. After healing, it makes good sense for therapists to emphasize small homework tasks that function to rehabilitate the client into full functioning.

DT:  I know you are also concerned about the person who simply complains to their primary care physician that they are feeling blue, and just gets a prescription for anti-depressants.  Please tell me your concern about that person.

Dr. Wager-Smith:  Yes the pharmaceutical industry has deluged the public with direct to consumer advertising telling them that if they feel depressed, they have a chemical imbalance, and that their physicians can prescribe medications that will effectively correct this imbalance for them. What these ads don’t say is the shocking finding that several very large, thorough, definitive studies have now been done that conclude that antidepressants are actually no better than placebo for mild to moderate depression. Only in the very most severe cases can antidepressants be shown to be more effective than placebo. At the same time as these data for antidepressants were falling through, data have been accumulating showing with the most stringent technique, the randomized clinical trial, that several types of psychotherapy have efficacy for depression.

DT:  What referrals do you believe that primary care physician should give?

Dr. Wager-Smith:  Based on the evidence base of clinical trials, I think primary care physicians should now refer their mildly and moderately depressed patients for psychotherapy rather than prescribing antidepressants.

However, I think this will be slow to happen for three reasons.

First, the preponderance of the evidence base has only recently shifted from drugs in favor of psychotherapy and I think many physicians are not up to date on that issue. The National Institute of Mental Health has contracted a website and continuing medical education (CME) course detailing the evidence base for psychotherapy (, so hopefully MDs will start to get updated.

Second, these physicians are continually bombarded in their offices with misleading propaganda from pharmaceutical reps, and there is no equivalent institution of representatives relentlessly promoting the case for psychotherapy (although I think we should consider creating such an institution!).

Third, the biological malfunction model has gained dominance with people, in part because I think having a biological (as opposed to purely psychological) explanation seems more solid, more objective, more believable. But now that our article offers a plausible biological scenario for how stressful events rather than biological malfunctions may cause depression, I’m hoping it will encourage a paradigm shift. I’d like to see people thinking that since psychosocial events can cause biological damage, it makes scientific sense that psychosocial treatments can support the natural healing process.

NOTE:  Dr. Wager-Smith is discussing unipolar depression.  Bipolar depression is different, and does respond well to medications in many cases.

Additional Note:  EMDR treatment has been used for depression with positive results, though it has not been directly researched.  Thus, EMDR is considered an experimental treatment for depression.

However, the following information which I shared recently with an insurance case manager convinced her to allow EMDR treatment for Bipolar Depression.  Research has demonstrated that EMDR can eliminate the symptoms of depression that are part of PTSD, which is a promising result.  Also, Cognitive Behavioral principles are integrated into the EMDR protocol.  Clients do experience spontaneous new positive beliefs arising within them after the distress from a negative experience is desensitized.  This occurs without doing the homework that is a required part of CBT therapy.

There is a great need for more research on depression, particularly EMDR treatment for depression.  It is our sincere hope that further research will arise from the excellent work already done by Drs. Markou and Wager-Smith.

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