"What's most hopeful about our field today is the fact that we have the technologies in hand that will get the answers to mental illness in ways never before possible," says Bryan Roth, M.D., Ph.D., and member of the Brain & Behavior Research Foundation Scientific Council. "We're going to know all the genes involved, and the circuits that regulate complex behaviors. And from the intersection of those two areas, I believe new treatments will become obvious. The insights we obtain will lead to discoveries that will transform the lives of people with these illnesses."
Dr. Roth speaks from the perspective of one who spends long hours in the lab, conducting research on how to design more effective drugs, based in part on technologies that he and his protégés have invented. NARSAD Grants have helped support new projects conceived by some of the lab's most promising doctoral students.
One technology invented by Dr. Roth and colleagues, based on Dr. Roth's 2008 NARSAD Distinguished Investigator Grant, goes by the acronym DREADD, for Designer Receptors Exclusively Activated by Designer Drugs. These manmade receptor molecules can be genetically introduced into any cell in mice, which are used to model human illnesses. The DREADDs enable scientists to switch "on" and "off" specifically selected nerve cells in the brain. In this sense, DREADDs are akin to a revolutionary method devised by another Brain & Behavior Research Foundation Scientific Council Member, Dr. Karl Deisseroth, whose optogenetics technology enables researchers to activate and deactivate specific neurons with beams of colored light.
Dr. Roth's DREADDs - which his lab has synthesized and bred into a line of mice, now available to researchers worldwide - provide a means of determining precisely which effects of a drug to attribute to the drug's action on its intended target(s), and which (if any) are generated by so-called "off-target effects," i.e., impacts on parts of the cell or neural circuitry that are not expected. Using DREADDs, Dr. Roth's team recently reported success in teasing out the details of neural circuitry that had long eluded scientists' best efforts - one that connects several brain regions involved in the biology of addiction.
Another of the lab's major efforts addresses the problem of how to optimally design drugs that hit multiple targets - the "shotgun approach." In designing a drug to hit a single target, it's relatively simple to set up screens that will show which molecules adhere best to the target. Multiple-target drugs present a much deeper challenge, since rational design implies biological knowledge of interactions among multiple parts of one or more neural circuits. The Roth team's approach turns the traditional drug discovery process on its head.
"Rather than screen every proposed drug molecule against every known target, we asked, 'Is there a way to predict the target?' With some colleagues, including my longtime collaborator Brian Shoichet at UCSF and his brilliant student Michael Keiser, we came up with computer programs that explore possible drug interactions mathematically." It's part of a field called chemo-informatics, and what excites Dr. Roth is that with it his team was able in a 2009 demonstration to sift 3,665 known drugs against hundreds of known targets and identify many interactions that no one had ever seen or anticipated. Even better, he said, the team actually validated 23 of these experimentally, and one was successfully tested in a mouse model.
In the context of the nation's impending research funding cutbacks and being at the brink of applying fabulous neuroscientific discoveries to treatment, Carol A. Tamminga, M.D., member of the Brain & Behavior Research Foundation Scientific Council, talks about the state of mental health research today.
"I believe we're really on the brink of being able to take the fabulous discoveries of neuroscience and apply them to the treatment of diseases," she says. "Our basic knowledge of the brain and how it works is growing by leaps and bounds, and opportunities for advancing our understanding of mental illness have never been better. But I worry about a precipitous loss of federal funding. I fear that psychiatry is one of the fields most vulnerable to cutbacks." She also worries about an either-or mentality regarding the allotment of resources for research and treatment development versus care of the mentally ill. "The two should be paired, not opposed, and we simply have to find a way to be able to do both."
Dr. Tamminga is chief of translational research in schizophrenia and head of the department of psychiatry at the University of Texas Southwestern Medical Center at Dallas, where she holds the Communities Foundation of Texas Chair in Brain Science. A major thrust of translational research in neuroscience now, she says, is toward "conceptual advances," approaches that go beyond simply trying to modify or improve existing modes of treatment.
Most existing treatments for mental illnesses, including antipsychotic and antidepressant drugs, target neurotransmitters, such as dopamine and serotonin that relay information between nerve cells across the synapses in the brain.
"These days our focus is moving to what happens after neurotransmission, to postsynaptic cell signaling and the relationship of those signaling systems to the functions of neuronal populations and, in turn, to the alterations in those functions that occur in psychiatric illness," Dr. Tamminga says. "As we learn more about neuronal population effects, we'll be able to close in on which particular effects are associated with which symptoms, and how we can modify those effects to relieve the symptoms."
Creative, novel approaches are what Dr. Tamminga looks for each year as she helps to screen the hundreds of applications for NARSAD Grants, which she's been doing since 1994. "We've never wanted to fund the same old thing, or projects for which other funding is readily available. We like areas that may be risky, but if they succeed might bring real change as has often happened with research initiated with NARSAD Grant support."
Throughout her years of association, and particularly at the present moment of uncertain funding, Dr. Tamminga has been a strong advocate for Brain & Behavior Research Foundation. "The Brain & Behavior Research Foundation funds people who are creative, people who bring in new methodologies and points of view," Dr. Tamminga says. In her view the combination of sufficient funding and a new generation of researchers "asking the right questions" are what will bring us to a new place in scientific discovery.
While scientists work toward a future in which mental illness is better understood and better treated, another hope long harbored by people with mental illnesses is being fulfilled - real jobs with real paychecks in safe and welcoming workplaces. J. Randolph (Randy) Lewis, Senior VP of Supply Chain and Logistics, Walgreen Co., spoke about a thoughtfully designed and highly successful program that he spearheaded to provide employment opportunities for disabled workers, including people with mental illnesses. When asked if he saw this as a responsibility for corporations - to offer employment opportunities for all people - he responded that, "Corporations only live on paper. It's the people in the corporations. Most people want to do the right thing, most people want to help."
Randy Lewis may be right. His program was launched in 2004 by Walgreen Co., and beyond the success within the company, it has become a model for other organizations and is being implemented by a number of major corporations, including Lowe's, Best Buy, Sears, Clarks and GlaxoSmithKline. "And the list keeps growing," he says.
Today he finds himself with a dual career, in his "day job" leading logistics and distribution centers at Walgreen Co. and as a trainer of this innovative and highly successful program to other corporations, even arch rivals in the marketplace. His division leads "boot camps" where managers of other corporations can come spend a week or two to learn the ropes of how it all works. "AT&T has gone through boot camp," he says. "Pepsico brought in a group of their international operators. A Brazilian company came and is starting a program in Sao Paulo, and I've spoken a couple of times to businesses in Germany."
What these executives see when they visit one of the Walgreen sites where the program is in operation are state-of-the-art, highly effective and cost-efficient distribution centers. What they may not initially see or realize is that there are disabled and able employees working side by side, often doing the same jobs, earning equal pay. At the company's distribution center in Anderson, S.C., the first site built specifically with the program in mind, 40 percent of the 600 workers are disabled, and, Mr. Lewis says, "It's the most cost-effective building in our chain and in the history of the company."
Randy Lewis's motivation for starting the program was personal. He has a son with autism, and like every parent with a child with a disability, he worried for his son's future. "Where is he going to be? Is he going to be engaged in the world, or is he going to be sitting alone all day staring at a TV or computer screen?" Mr. Lewis was certain that in his own company there were any number of jobs that his son and other disabled people could perform, "but," he says, "first they had to be able to get in the door.
"We've learned that sometimes a job is a lot more than a job," Mr. Lewis says. "Some of these folks never knew what a weekend was. For them every day was like every other day. Now they have weekends, they have income, they're like everyone else."
May is Mental Health Month
May 26 in Toronto, Canada
Frontiers in Mental Health
Co-sponsored by the Graham Boeckh, Gairdner and Brain & Behavior Research Foundations with presentations by Foundation Investigators and Scientific Council members. Benita Shobe, Brain & Behavior president and CEO, will give opening remarks.
June 22 in Cold Spring, N.Y.
Brain & Behavior Research Foundation, St. Johnland Nursing Center and Cold Spring Harbor Laboratory Research Event
Presentations by Brain & Behavior Research Foundation Scientific Council members on Depression and Bipolar Disorder with Q&A. Details: 7 p.m. at Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, N.Y. Refreshments following Q&A.
Fight Teenage Depression: Raising Awareness That 'It's not a phase'
To date, more than 500 "It's not a phase" wristbands have been sold. To purchase a wristband and support brain and behavior research go to www.itsnotaphase.org. Follow the cause on Facebook:www.facebook.org/fightteenagedepression.
June 13 in Harrison Township, Mich.
19th Annual Michigan NARSAD Grants Golf Classic
Gowanie Golf Club
For more information contact Elizabeth Puleo-Tague at 313-882-1482
July 22 at Rock Hill Golf & Country Clubin Manorville, N.Y.
5th Annual Chrissy’s Wish Memorial Golf Outing
Chrissy’s Wish was established in memory of Christina Rossi, and to honor all those who continue their struggle with mental illness. Chrissy passed away at the age of 26, suffering from depression and bipolar disorder. As a result of several fundraising events, Chrissy’s Wish has raised more than $170,000 for the Brain & Behavior Research Foundation.
July 23 in Pleasant Grove, Utah
Silver Linings For Loved Ones Family Hike in memory of Brian Taylor
Click here for more details on Team Up events and instructions on how to host your own event!