In May 2016, the Library of Congress and the John Kluge Center hosted a symposium on Can Depression be Cured? at which four of the top medical researchers into depression and its treatments presented their latest research findings. A full unedited transcript of the presentations can be found here and the video is here

The first presentation was given by Dr. Philip Gold who has been a member of the Library of Congress’s  Scholars Council since 2004. He received his undergraduate medical degrees at Duke University and his post-graduate medical training at the Harvard Medical School.  He has been at the NIH Clinical Center since 1974 where he served as chief neuroendocrine research in the NIMH intramural research program. I’ve summarized his address below and over the coming days, I’ll try to do the same for the other addresses, before summing up with a reflection on the research.

The main findings in Dr. Gold’s research are really quite stunning and should result in a major re-evaluation of the understanding of depression. Here’s a simplified summary of the findings followed by a brief explanation of each one:

1. Depression is a disorder of the human stress response.

2. Depression is a disease which involves brain tissue loss and damage. 

3. Anti-depressants work by increasing the growth of brain cells and the connections between them.

4. Depression causes serious damage to the rest of the body

5. The best treatment for depression at present is a mix of talking therapies and medication

Main Finding 1: Depression is a disorder (dysregulation) of the human stress response

The stress response is our reaction to stressors in our life (physical, psychological, spiritual, etc.). For example, if you are being chased by a bear the stress response should kick in to maximize chances of survival. The stress response includes:

  • Fear-related behaviors and anxiety.
  • A decreased capacity for pleasure (in order to focus attention on the threat).
  • Inflexible mood and cognition.
  • Stress hormone production (especially of cortisol and norepinephrine).
  • Redirection of fuel to the bloodstream and the brain through development of insulin resistance.
  • Increase of inflammation and coagulation (blood clotting), both priming the system to respond to possible injury.
  • Inhibition of neurovegetative program, meaning suspension of appetite, rest, sleep, sexual desire.
  • Increased neuroplasticity (the brain’s ability to form new neural connections) and neurogenesis (growth of brain cells).

In melancholic depression (which affects 35% of those with major depression), the stress response is disordered in that when triggered it does not terminate quickly enough or sufficiently enough. It gets stuck in the “on” position, resulting in:

  • Increased and prolonged fear-related behaviors and anxiety.
  • Inhibition of the capacity to anticipate or experience pleasure.
  • Inflexible mood and cognition (mood and thinking patterns are in a rut).
  • Increased and prolonged stress hormone production.
  • Increased insulin resistance in order to redirect fuel to bloodstream and brain.
  • Increased and prolonged inflammation and coagulation.
  • Increased and prolonged inhibition of neurovegetative programs (appetite, rest, sleep, sex).
  • Decreased neuroplasticity and neurogenesis.

Main Finding Two: Depression is a neurodegenerative systemic disorder rather than a chemical imbalance.

There is chemical imbalance in depression but the primary cause is a loss of brain tissue in key areas (and abnormal increase of brain tissue in one key area).

A number of areas in the brain are physically changed in this disorder of the stress response.

1. The subgenual prefrontal cortex is reduced in size by as much as 40% in patients with familial depression. The subgenual prefrontal cortex:

  • Regulates and restrains the brains fear system.
  • Plays a large role in self-assessment.
  • Estimates the likelihood of punishment or reward.
  • Modulates the pleasure and reward center.
  • Restrains cortisol secretion.

When the subgenual prefrontal cortex is decreased in size all of these functions are similarly decreased resulting in excessive anxiety, feelings of worthlessness, decreased pleasure, and increased production of stress hormone.

2. The amygdala increases in size and goes into overdrive in depression and this further restrains the working of the subgenual prefrontal cortex.

3. The ventral striatum is significantly reduced in size during depression. This area is the pleasure and motivational center.

4. The hippocampus serves multiple memory functions and is the main place where neurogenesis (growth of new brain cells) occurs. Its size is significantly reduced in depression.

Summing up the loss of or damage to brain tissue, Dr. Gold said: “There’s more loss of tissue in depression than there is in Parkinson’s disease!” “Depression as a full-blown disease,” he warned, “a systemic full body disorder with neurodegenerative aspects and is a progressive disease, much more serious, I think, than we had previously appreciated.”

Main Finding Three: Anti-depressants work by improving neuroplasticity and neurogenesis

Almost all antidepressants significantly improve neuroplasticity and neurogenesis.  There are few other (if any) compounds which actually increase neurogenesis, and people are experimenting using antidepressants to try to treat disease of the retina, for instance, to get neurogenesis active there and other sites of the body. The challenge for the next generation of anti-depressants, then, is to develop compounds that promote neurogenesis and neuroplasticity.

Main Finding Four: Depression damages the rest of the body

The pathological losses or gains in tissue in specific sites set into motion pathologic changes outside of the brain:

  • They’re responsible for the premature onset of coronary artery disease, stroke, diabetes, and osteoporosis.
  • Increased cortisol (growth hormone) secretion affects every cell in the body.
  • Increased insulin resistance and cholesterol levels increases inflammation, produces bad lipids, and increases clotting.
  • Premenopausal women with major depression have much higher incidence of osteoporosis
  • Depression is really the tip of the iceberg. The syndrome is serious and systemically widespread.
  • Patients with untreated depressive illness lose approximately seven years of life, much as untreated hypertension predictably shortens a life.

Main Finding Five: The best treatment for depression at present is a mix of talking therapies and medication

Depression is a serious disorder that impacts the whole body, it is progressive, and it needs to be treated.

60% of people with depression in the United States remain untreated.

The most effective way to treat depression at present is a combination of talking therapies and medication.

Data shows that people who successfully respond to talking therapies have positive physical changes in the three key areas of the brain that are affected in depression: the subgenual prefrontal cortex, the amygdala, and the ventral striatum.

As for the future, there are trials ongoing of new medications (like ketamine) which are producing rapid remission of depression (within 1-2 hours).

There are also psychosurgery trials involving the implanting and stimulating of electrodes in the subgenual prefrontal cortex which are producing immediate and sometimes lasting response.

Magnetic resonance treatments (MRI) are also being used to treat areas of depressed patients brains in a non-invasive way.

Training in resilience is also proving helpful:

  • The American Psychological Association defines resilience as the process of adapting well in the face of adversity, tragedy, trauma, threats, and even significant sources of threat.
  • Mild to moderate controllable stress early in life can have an inoculating effect.  Such experience leads to increased neuroplasticity and neurogenesis, and increases the size of the subgenual prefrontal cortex.
  • An enriched, nurturing environment in early life with exposure to manageable novelty increases resilience later in life.
  • Positive emotion, optimism, loving caretakers, flexibility, the capacity to reframe adversity, and strong social support also increase resiliency.
  • Altruism, commitment to a valid cause, a capacity to extract meaning from adverse situations, and a tolerance for emotional pain and sadness promote resiliency as well.
  • Annette

    Dr Murray.
    I cannot overstate how helpful it has been that you are “curating” these different sources of depression research and posting them here!!! I have a number of people in my life who suffer from severe depressive disorders and GAD. This type of information helps me to build empathy and allows me to inform others of how terrible depression is. It has astonished me how little we speak of depression (and other disorders) in our church and how little the average Christian knows about this, let alone knows how to come along side a sufferer of depression.

  • Cameron Shaffer

    Dr. Murray,

    Thank you for this. I have a couple of questions about this and would love to hear your perspective.

    1) If a combination of talking therapies and medication is the best current treatment, do we know how talking therapy repairs damage or loss of brain tissue? It seems counter intuitive to me that talking therapy could have that kind of measurable effect.

    2) Since the depression described has such significant, measurable medical effects, does that mean that the vast number of people currently taking medication for MPP, PDD, and similar disorders are suffering these effects? Or are there a significant number of people who express “subjective” symptoms, but do not possess the “objective” brain tissue deterioration?

    3) As a pastor, what counsel would you give me for assisting people suffering from depression either in developing resistance and/or in being a source of talking therapy? Or would you recommend not at all?

    Thanks again for posting this.

    • David Murray

      Good questions, Cameron. I hope to answer them when I write a post reflecting on this and the other research from this symposium. Just briefly, though, on your first point: in other research, PET scans have shown that the brains of abused children are physically different to those of children raised in loving homes. However, after these children have received loving care and counsel over a period of time, their brains show signs of repair and of returning to normal. So it shouldn’t surprise us that talking therapies for depression can also impact a damaged brain in a positive way. I know it seems counter intuitive but if there’s one thing that brain research teaches us to expect, it’s the unexpected. There is much that remains mysterious about the brain and its connections to the body and the soul.

      • Cameron Shaffer

        Dr. Murray,

        Thanks for the reply. I’m looking forward to the rest of the summaries and your reflections.

      • Angelina

        We are created for relationships – talk therapy needs to be done with caring individuals that you have formed a safe bond with.
        Just my experience and 2 cents :)

  • Simon Agar

    Hi Dr Murray

    Thanks for another great article. I became an instant fan of you and your work when i discovered the Double Dangers: Maximizing and Minimizing Mental Illness blog and it’s predecessor The problem with “mental illness”. I look forward to more. I have bipolar disorder and GAD and run a support group in Port Elizabeth, South Africa for people with mental illnesses. I will forward this link to everyone i can.

    God bless

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  • antione johnson

    I am a cognitive educator for children and youth diagnosed with serious emotional and behavior disorders. I first learned of Neuroplasticity in 2005 while researching information to help veterans suffering from PTSD; I read several books (How God Changes the Brain) Andrew Newberg and (Train your Mind Change your Brain) Sharon Begley. I’m very excited to be able to encourage my young students about this new research, whom many have been told that there is no hope for their many issues resulted from abuse and neglect. Neroplasticity is the hope of thier future.

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