Treatment-Resistant Depression (Part 3): Maybe It's Time for a 'Noble' Prize

NEW YORK - NOVEMBER 16: HDRF Founder and Chairman, Audrey Gruss attends the Hope for Depression Research Foundation Seminar a
NEW YORK - NOVEMBER 16: HDRF Founder and Chairman, Audrey Gruss attends the Hope for Depression Research Foundation Seminar at Time Warner Center on November 16, 2009 in New York City. (Photo by Henry S. Dziekan III/Getty Images)

Alfred Nobel's decision to transform the vast fortune he earned by inventing weapons of destruction into a force for good has proven to be one of the most important philanthropic acts in history. Honoring scientists, writers, and activists who labor in obscurity for years inspires countless other people to do so. It also reflects the innate human drive to be the first, a drive that has fueled scientific research since well before Archimedes shouted, "I have found it!"

That drive may be innate, but it may no longer always be in our best interest, particularly not that of those who stumble from doctor to doctor, psychiatrist to psychiatrist, and even acupuncturist to acupuncturist, desperately trying to lift the veil of depression that haunts their every waking hour.

There is definitely more information sharing among researchers than ever before. But even with the Internet, which we thought was going to level the playing field, scientists continue signing nondisclosure agreements as fast as you can say "dotted line."

This has led to what is called the "silo" effect -- a myriad of individual projects with very specific parameters. While other researchers may be aware of your work, major breakthroughs are closely guarded until they are published. These projects are also constrained by whoever's funding it -- the university, a government agency, a pharmaceutical company, and/or a foundation. They are all fully vested in seeing you make a significant discovery that will justify their financial investment and enhance their reputation.

Research into treatment-resistant depression -- which affects the approximately 50 percent of people who don't respond to existing antidepressants -- is particularly hampered by this "silo" effect, because mental "disorders" manifest in so many different ways in so many different parts of the brain, all of which are connected: neurotransmitters, receptors, synaptic action, cellular structures, genetic sequencing, communication pathways, mysterious neural circuitry deep in the brain, and a wide range of other influences, particularly stress and hormonal changes. To study each individually without real-time awareness of progress in other areas seems narrow-minded.

If you're a neuroscientist who's fought for some of those limited research dollars so you can spend years working with enthusiastic grad students and not-so-enthusiastic mice to test a specific group of molecules that you suspect might cheer some the latter up a little bit, it has to be distressing to learn that a researcher across the country is about to publish a paper about a similar group of molecules or gene therapy that makes a lot of his mice deliriously happy, thereby making your findings far less significant.

What no one mentions is the fact that if the two of you had been sharing results from Day One, you might have found synergies between the two approaches that would have resulted in more mice jumping for joy in way less time.

In 2010 a woman named Audrey Gruss decided to do something about this seemingly intractable dysfunction. She created a new paradigm for research into treatment-resistant depression.

Like many impassioned philanthropists, Mrs. Gruss is driven by a personal story: her mother's decades-long struggle with major depression. Unlike many impassioned philanthropists, however, she has the medical and business background to hold her own in complex scientific discussions.

So, rather than simply enabling researchers to go off and follow their own individual research, her HOPE for Depression Foundation (yes, named after her mother, Hope) has created a special task force of world-renowned neuroscientists who work together on a common path toward specific benchmarks and goals. Most importantly, they share their ongoing results on a real-time basis. This enables them to identify weaknesses in each other's experiments and use each other's successes to refine and even redirect their own work -- without having to worry whether their funding organization will question their every move.

The search for treatments has always been hampered by the fact that we still don't really know what causes depression. So the first goal of Mrs. Gruss' HOPE Task Force -- before even trying to develop a cure -- is to find that cause. The distinction is significant and often overlooked.

The fact that some people respond to medications that change the way certain messages zoom around the brain doesn't mean that the cause of depression is always misbehaving neurotransmitters (e.g., serotonin, norepinephrine, or dopamine). That may just be one of the symptoms.

The fact that other people respond to supplements and meditation doesn't mean that malnutrition and stress are the cause. It may just mean those are two potential triggers for depressive episodes.

The fact that a good number of depressives have a little abnormality at the 5-HTT or some other gene doesn't mean that's the cause of depression. It may simply mean that they are more predisposed to depression, especially when under stress, than someone else might be. Many other people with those abnormalities aren't depressed, and many who are depressed don't have it.

The fact that stimulating one specific area of the brain helps some people doesn't mean that the same circuit is out of whack in others.

Cancer researchers in the 1970s faced a similar dilemma. After a century of looking for cures, they still didn't really know the cause of different cancers. Since then, they have made such great strides in their understanding of fundamental cell biology that they are often able to identify early indicators (biomarkers) of different cancers before the cells become dangerously malignant.

Hope for Depression would like to do the same for treatment-resistant depression: identify its biological origins, develop diagnostic tests to identify its subtypes, and eventually help develop personalized cures.

Mrs. Gruss' determination to cure treatment-resistant depression once and for all may be a bit quixotic, as all true quests for medical breakthroughs must be. But the fact that her organization recognizes the importance of getting leading scientists to work together to get to the true bottom of things is, in itself, noble, in a way that I think would have garnered Alfred's approval.