Darkness Visible

13 August 2014 by Susan E. Swanberg, posted in Blog Posts

No light; but rather darkness visible

Served only to discover sights of woe

—John Milton, “Paradise Lost”

Moon Over the Santa Catalinas

Full moon over the Santa Catalina Mountains. Credit: Susan E. Swanberg

A Terrible Toll

I couldn’t help but gasp when I heard about the death of the well known actor/comedian. In the throes of the malady author William Styron called “darkness visible,” the beloved figure apparently took his own life. We knew he’d faced his nemesis before, that Caliban called depression, but the man would always recover—or seem to recover—smiling and miming and acting his way back to life’s roiling heart again. This time it wasn’t to be.

According to the World Health Organization, more than 350 million people across the globe suffer from depression, the world’s leading cause of disability. More women than men suffer from depression, but men are more like to die by suicide than women. More than 1 million people around the world commit suicide each year.

What is Depression?

Depression is a disorder of the brain, probably caused by a complex interaction of biological and environmental factors—nature and nurture. Depression is moderately heritable, that is the tendency to become depressed is influenced by your genes, however environment stressors are also risk factors for depression.

Depression is not just “feeling blue.” It’s a persistent emotional state, lasting longer that a couple of weeks, that interferes with your ability to cope with the usual challenges of life.

You can’t make someone get over depression. Comments like “think of all the good things in your life” or “buck up, it’s not that bad” aren’t helpful. People with depression are not cowards nor are they weak or morally deficient. They have a biologically based disorder influenced by social, psychological and other external factors.

Symptoms of Depression

Gracie in the Moonlight

Horse in the moonlight. Credit: Susan E. Swanberg

Symptoms of depression can include:

  1. Persistent sad feelings sometimes accompanied by anxiety or feelings of emptiness
  2. Feelings of guilt, worthlessness, helplessness or hopelessness
  3. Irritability or restlessness
  4. Loss of interest in one’s usual occupations
  5. Fatigue, decreased energy, lack of concentration, memory problems, problems with decision making.
  6. Insomnia, early morning wakefulness or excessive sleep
  7. Change in appetite—either overeating or appetite loss
  8. Thoughts of suicide or suicide attempts
  9. Physical complaints including pain, headaches, aches or digestive problems

(Based upon an NIH publication on depression)

Depression’s a hard nut to crack because the causes are so complex. There’s been quite a bit of research on depression, and more studies are underway, but as with many complex biological conditions, the cure has been elusive—in part because the stigma associated with depression often keeps people from seeking treatment.

The National Institute of Mental Health (NIMH) funds research on depression. You can read about ongoing NIMH depression studies here.

Common laboratory mouse. Shutterstock http://tinyurl.com/ljyqeqv

Common laboratory mouse. Shutterstock

The Link Between Learned Helplessness and Depression

In May of 2014 Bo Li, a researcher at Cold Spring Harbor in New York, published his group’s research on resilience and the brain. Using a mouse model for depression, the “learned helplessness” (LH) mouse, Li and his team examined neurons at the front of the brain in the medial prefrontal cortex (mPFC)—neurons that were known to become overactive in the brains of depressed people.

Learned helplessness (LH) is a behavioral reaction to stress. If an animal is forced to endure an unpleasant stimulus, like an electric shock, for a long enough period with no means of escape, that animal will continue to endure the shock even when an escape route later becomes available. Learned helplessness is associated with depression in people. The mouse is not a perfect model, but mouse studies can be a good starting place for research.

In an intricate series of experiments, Li’s team linked activation of mPFC cells to learned helplessness behaviors. The mPFC cells of mice that stopped seeking relief from a series of electric foot shocks, even after an escape was provided (LH mice) were activated compared to mPFC cells of resilient mice—mice that sought a place of safety. Most tellingly, when the mPFC cells of resilient mice were artificially stimulated, these mice also exhibited learned helplessness behaviors.

There’s still a long way to go before we fully understand how the brain functions in a depressed person, but Li’s study suggests that the mPFC pathway could be a good target for depression drug development.


The Santa Catalina Mountains during monsoon season.

The Santa Catalina Mountains during monsoon season. Credit: Susan E. Swanberg

None of this research will bring him back, but for the 1 million people every year who will suffer from depression, perhaps there is some sunlight on the horizon.

What Can You Do About Depression?

If you’re depressed, there are treatments that can help. Medication, cognitive behavioral therapy or a combination of the two can make a difference.

If you or someone you know needs help dealing with depression, call the National Suicide Prevention Hotline at 1-800-273 TALK (8255).


Wang, M., Z. Perova, B.R. Arenkiel, B. Li, “Synaptic modifications in the medial prefrontal cortex in susceptibility and resilience to stress,” The Journal of Neuroscience 34(22): 7485-7492.

For an excellent article on the science and history of treating depression, see Siddartha Mukherjee’s 2012 New York Times article.


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