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 percent 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 percent in patients with familial depression. The subgenual prefrontal cortex:
- Regulates and restrains the brain’s 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 that 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.