Saving Troubled Minds

Whenever Patient A is close to a sharp object, he has violent mental flashes. He is afraid he will get cancer by touching certain objects, so he compulsively washes his hands. He hears loud buzzing noises, which he silences by pressing his flattened palms hard against his ears. Sometimes, crosswalk lines look incorrectly drawn, so he'll walk outside the lines as a form of protest. He used to do well in school, but now in the 10th grade, he's failing all his classes. His mother is beside herself with worry.

Patient A isn't real, but he might as well be. He's a composite of young people who seek treatment at UCLA, where researchers and clinicians are breaking new ground in the battle against schizophrenia. The war is being fought on two fronts: the clinic, where mental health professionals are helping teens like Patient A learn to cope in a world turned cruel and chaotic, and the lab, where researchers are examining molecular changes in the brains of young people at high risk for schizophrenia.

If this lab research goes well — and there are early indications at UCLA and elsewhere that it will — a 12-year-old who is sliding toward psychosis may be able to take drugs or undergo gene therapy to significantly alter the course of the disease or perhaps forestall it entirely.

"That's many years off, but what we have accomplished already gives us some clues that make it sound not so science fictiony," says Tyrone D. Cannon, lead researcher in the effort and director of UCLA's Staglin Family Music Festival Center for the Assessment and Prevention of Prodromal States, or CAPPS. The first part of the center's name comes from the Northern California family of winemaker-venture capitalists and the music festival they host each year to raise money for research into schizophrenia and other serious mental disorders.

Schizophrenia is shockingly prevalent. One out of 100 people will develop the disease at some point in life, usually between the ages of 16 and 25. Many live with family members or in assisted living centers; others bounce from the streets to jail to psychiatric wards. Side effects of antipsychotic drugs available today — lethargy, weight gain, muscle stiffness and a deadening of facial expressions — add insult to injury. Fully three-quarters of patients fall off their medications. Many sufferers never get drugs at all.

Most people with schizophrenia are diagnosed after a psychotic episode, when the disease is full blown and harder to treat. At this point, explains Cannon, patients have an unshakeable conviction in the reality of their delusions and hallucinations. Appeals to reason are futile.

So researchers in recent years have turned their attention to younger people with early-onset symptoms that precede the transformative psychotic episode. (Fifty percent of these patients will go on to develop full-blown schizophrenia.)

At this early stage of the disease, known as the prodrome, tweens and teens are mostly aware that the vexing sounds and sensations are just their mind playing tricks on them. For these early-onset patients, new scientific studies suggest that antipsychotic drugs, despite their unpleasant side effects, "seem to make a difference in reducing the rate of transition to psychosis," says the center's clinical director, Mary Patricia O'Brien. Moreover, anecdotal evidence indicates that young people experiencing pre-psychotic symptoms benefit from psychosocial interventions, explains O'Brien, who is married to Cannon.

Worldwide, there only are a handful of research clinics devoted to the prodromal phase of schizophrenia. One of the most highly regarded is CAPPS, which is part of UCLA's Neuropsychiatric Institute. Cannon, 43, established the clinic shortly after he came to UCLA in 1999 as an up-and-coming researcher. Tall and boyish-looking, Cannon is a Boise, Idaho, native who favors blue jeans in the office. He is articulate, soft-spoken and familiar firsthand with the consequences of the disease he fights.

One of the scientist's relatives suffered from schizophrenia and another from bipolar disorder, which, like schizophrenia, is probably related to a biochemical abnormality in the brain. Listening to his parents, Doug and Jan, talk about these relatives, and later meeting them, excited Cannon's youthful curiosity about how they came to be so different from everyone else in his family.

Cannon attended Dartmouth, where he read the classics and studied psychology, paying particular attention to severe psychopathologies like schizophrenia, which he found especially fascinating. Intending to pursue a career as a clinical therapist, he studied at USC under Sarnoff Mednick, the scientist perhaps best known for his study of Danish children born to schizophrenic mothers. After USC, Cannon came to Westwood to do clinical training at the Neuropsychiatric Institute. But he became increasingly skeptical of the ability of psychological treatments like talk therapy to do much good for very sick people whose illnesses were tied to neurochemical imbalances in the brain.

What really interested Cannon was finding a cure. He left the therapist's office for the research lab and began his quest in earnest.

Despite intense investigation over many years and across many continents, little was known about the underlying causes of schizophrenia, aside from the fact that the disease was linked to both genetics and disruptions in utero, such as a viral infection in the mother or a shortage of oxygen to the fetal brain. One of Cannon's first research projects, at the University of Pennsylvania, was a study that looked at genetic and environmental causes of schizophrenia in same-sex twins born between 1940 and 1957 in Finland. Cannon's team showed that genetic factors accounted for more than 80 percent of schizophrenia cases, while less than 20 percent were due to environmental factors such as in utero disruptions.

The results of the study were just beginning to seep into the medical and research communities when UCLA began looking for a schizophrenia researcher for a new professorship endowed by Garen and Sharalyn Staglin, both 1966 UCLA graduates. Like Cannon, the Staglins know all too well the toll schizophrenia takes on a family. And, like the man who would soon run their eponymous center, they wanted to help find a cure.

Garen and Sharalyn, who goes by Shari, met at a dorm party at UCLA in the mid-1960s.

Garen was studying engineering, Shari international affairs. After finishing their studies at UCLA, the couple moved to Northern California so that Garen could pursue a business degree at Stanford. They married right after graduation. At the ceremony, a friend locked their wrists together with handcuffs.

Shari, who went on to earn an M.P.A. from NYU, worked as a legislative aide and ran her own welfare-to-work nonprofit. Garen served on a destroyer in Vietnam and made his mark in information technology. In 1985, Garen and Shari bought a 50-acre vineyard on Rutherford Bench, not far off the main highway that runs through Napa Valley. They had two children, Brandon and Shannon '01.

When schizophrenia happens in a family, it's like being struck by lightning, says O'Brien. In the summer of 1990, lightning struck the Staglin family. Brandon, then an 18-year-old freshman at Dartmouth, had a psychotic break.

In 2004, writer Julian Guthrie of the San Francisco Chronicle interviewed Brandon and his parents about what happened. The story she wrote was painstakingly detailed and "completely accurate," Garen says. Today, Brandon, 34, is on medication and doing well. He works for the family business as a writer and Web designer. He is also a poet. He wrote a paean to Napa Valley wine country that appears on the home page at www.staglinfamily.com. Brandon is trying to move on with his life, so the family lets the Chronicle story stand as the official record.

In 1990, Guthrie wrote, Brandon had everything in the world going for him. He had a 4.0 grade point average in high school and scored a perfect 800 in the English portion of the SAT and a 785 in math. He played soccer and hoped to become an astronautical engineer.

That summer, Garen and Shari rushed home from a business trip in Paris. Brandon had been picked up by police and placed in a psychiatric hospital. In the days leading up to his hospitalization, Brandon told Guthrie, "half of my identity vanished." He wandered the town of Lafayette east of San Francisco, "covering his right eye as he walked, fearful another personality would fill the void."

Garen and Shari were determined to help their son beat the illness. They sought out the best doctors, read scientific literature and met with researchers. As the Staglins learned more, they decided to make the search for a cure their life's work.

In 1994, the couple put on a music festival at their vineyard to raise money for research and treatment of physiological brain disorders. The Staglin Family Music Festival for Mental Health was a huge hit. Now in its 12th year, the annual festival has raised more than $30 million for treatment and research. The event is a feast for epicures and music lovers but also a forum for discussion of the latest research in mental health. Roberta Flack and Brian Wilson of the Beach Boys have performed. Top chefs prepare five-course dinners, served poolside under the stars in the Staglins' lusciously landscaped backyard. Winemakers donate their best vintages. Leading mental health scientists discuss their latest research. The Staglins underwrite all expenses.

In the late 1990s, Garen and Shari gave $1 million to UCLA to endow a professorship that would focus on finding the causes and cure for schizophrenia and other mental disorders. They set conditions: The appointment had to go to a "walk-on-water scientist" who would push hard at the boundaries of knowledge. "The projects we like to fund are these high-risk, high-reward things," Garen says. Convinced that the fight against mental illness must involve a multidisciplinary, holistic approach, the Staglins also wanted someone who would work collaboratively with other UCLA departments and schools, as well as peers around the world.

"Have you met him? Isn't he totally that person?" Shari asks about Cannon.

Newly installed at UCLA, Cannon began thinking about how to focus his work. "He came to us and said, ‘How about if we prevent this stuff before it even starts,' and I said, ‘Yes!' " Shari says, nearly jumping out of her chair.

The Staglins gave $1.2 million in seed money for CAPPS. The funds went for early research that would enable Cannon to win awards of $11.5 million from the National Institute of Mental Health. The Staglins have since endowed CAPPS with $3.5 million and contributed $4 million to the Staglin Music Festival Center for Cognitive Neuroscience at UCLA. The center explores the human brain in order to understand the workings of the mind. All told, the Staglins have given about $10 million for mental health research and treatment at UCLA.

In the seven years since he has come to UCLA, Cannon has "dramatically exceeded our expectations," Garen says. The researcher's first major breakthrough was reported in 2002. Working with the same brain maps of the Finnish twins, Cannon found that schizophrenia patients have significant reductions in gray matter in regions of the brain that synthesize information. The reduced gray matter indicates that neurons are making weaker connections in these areas that integrate, interpret and organize information.

Three years later, Cannon published findings that moved research closer toward finding a way to prevent schizophrenia. Susceptibility to the disease is associated with several genes. One is called DISC1. Looking again at the brain maps of the Finnish twins, Cannon discovered a DNA sequence variation in a region partly in DISC1 and partly in a neighboring gene called TRAX. Someone who has the sequence variation is at 10 times the normal risk for schizophrenia. Cannon's hope is that one day it may be possible to fix the sequence variation so that the DISC1 gene functions normally.

Just one of the many reasons why the Staglins' walk-on-water scientist sounds so hopeful.

"I have to say I'm really excited by what we're doing these days," Cannon says.

Published Oct 1, 2006 8:00 AM