Unraveling a Cruel Mystery of the Mind

Meggin Hollister had longed to unlock the secrets of her big sister’s mind.

For 18 years, she wondered why schizophrenia snatched away Annick, the pretty sister she adored, the A student, the sophomore class vice president. Meggin was only 12 when the Greek chorus started in Annick’s head, when the demons drove the 16-year-old to the streets, then to padded solitary confinement cells.

As a high school student in La Habra, Meggin looked for answers to what caused her sister’s illness in college biochemistry texts. As an undergraduate at USC, she hung on the words of noted researchers. Finally, as a graduate student there, she got to test a theory of her own, based on a medical complication her mother had while carrying Annick in her womb.

Meggin suspected a possible link between schizophrenia and a pregnant woman’s immune system, which can produce antibodies that harm the developing baby’s brain.

She spent months looking for that link in a sample of medical records of pregnant women and their children. Finally, in February 1995, Meggin waited impatiently in a crowded research lab until the computer spit back her statistical analysis. She stared at the screen in disbelief.

“Oh, my God,” she thought. “The implications. . . .” She checked and rechecked her data, then burst into her professor’s office with the news of her discovery.

In January, the Archives of General Psychiatry published Meggin’s finding.

The major medical journal hailed her paper as a “landmark study.” Experts say Meggin’s work could help to pinpoint one of the causes of schizophrenia and lead to possible ways to prevent it. Hers is part of a growing body of research indicating that obstetrical complications, rather than social conditions, can lead to the disease.

Meggin’s finding is a remarkable coda to her family’s long struggle to help Annick. She, her parents and her brother have fought through their anguish and are now in the forefront of the battle against schizophrenia.

Patsy and Hal Hollister had expected to spend their retirement in the south of France and on their eight-acre property in La Habra Heights, which includes a vineyard and an avocado grove. Now, they work full-time overseeing a national organization in Brea that has raised nearly $500,000 for research into mental illness and for mental health groups in Orange and Los Angeles counties.

Their son, John, 35, became interested in medicine because of Annick and works in marketing for a large Philadelphia-based pharmaceutical company. He helps his parents and Meggin in their work.

And Meggin, 30, recently won a $60,000 “Young Investigator” grant from the country’s largest public donor of mental health research funds.

“It’s an amazing story,” said Constance E. Lieber, president of the National Alliance for Research on Schizophrenia and Depression, which awarded the grant. “[Schizophrenia] can be very destructive in some families--husbands and wives [can] blame each other for their child’s problems. . . .

“This is a most unusual story because it reaches into the [Hollisters’] other children. . . . They are people who have given their lives over to trying to find the cause.”

The Hollister family is ecstatic about Meggin’s finding.

“I thought, ‘Oh, Meggin does care a lot about me,’ ” said Annick, 34, who lives at a board-and-care home in the Eagle Rock area of Los Angeles.

Patsy and Hal said they had known in their hearts that a biochemical glitch caused Annick’s mental illness. But every bit of confirmation helps.

“We were so far beyond considering the guilt,” said Patsy, 62, a nationally recognized mental health advocate. “But there’s always a feeling of, ‘If we had just done that or just done this. . . .’

“[Meggin’s finding] was a wonderful, happy irony. . . . It made you that much more pleased at being a parent. You know, just ‘oooooooh.’ ”

Schizophrenia is a severe mental illness that afflicts about 2.5 million Americans, usually striking in the late teens or early 20s. It torments its victims with scary voices, hallucinations and irrational thoughts.

There is no cure, but new antipsychotic drugs and rehabilitation programs--including psychotherapy and job training--can help schizophrenics lead manageable lives.

The Hollisters never bought the theory popular in the late 1970s that blamed bad parenting for causing schizophrenia. They didn’t listen to the psychiatrist who faulted John because he appeared “controlling” in a personality test that required him to make a crayon drawing.

But you never stop wondering what snapped, said John, who now is married and has a 2-year-old daughter. Not after you see your disheveled sister in the padded cell of a mental hospital, with nothing for company but a mattress.

“You ask, ‘Why was it my wonderful sister? Why was it our family?’ For the retrospective, and for the prospective. I look at my little daughter and say, ‘I hope we haven’t passed something on to you.’ ”

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Annick was difficult. She was the sort of child who pushed when she should have pulled, who touched a hot stove twice. She threw tantrums.

But it was nothing she wouldn’t grow out of, her parents thought.

Patsy and Hal, who have no family history of mental illness, never considered schizophrenia.

Annick was born in Paris, the city that inspired her French name. Her father was an oil industry executive whose business took the family all over the world.

When she was born, her mother thought she looked perfect, with delicate features and olive skin. But she was a colicky baby who cried nonstop.

Growing up in Houston, then La Habra Heights, Annick’s artistic side emerged. She cut strings of paper dolls for her little sister, and the two played on her bed for hours. She loved to dance in her pink tutu and satin leotard, and draw her own picture books.

As a teenager, Annick was leggy and tan, funny and smart. To her parents’ dismay, she started to smoke marijuana and ditch school.

In 1978, she dropped out after serving one day as sophomore vice president. Later that year, she had her first psychotic episode at a Halloween party. She was howling at the moon when the police came to haul her home.

Her bewildered parents put her to bed, but Meggin’s screams soon brought them running. Annick had tried to slit her wrists.

For the next 10 years, she was out of control. She spent half the time in mental hospitals and the other half on the streets.

“As a parent,” Patsy said, “you want your child to experience joy. With Annick, it was so sad to see that light appear--and then disappear.”

Sometimes, her family lost track of her for months. Once, she was picked up, catatonic, beside a ditch in El Paso. Another time, she showed up with a black eye, wrapped in a worn blanket and nothing else, on her grandmother’s front doorstep in Riverside. She talked gibberish about how she saw God in the setting sun.

“Amazing, that she survived it,” her mother said. “Amazing.”

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Neither John nor Meggin remembers the details of Annick’s unraveling. John said he thinks he blocked the memories out. A year after his sister’s illness was diagnosed in 1978, John left home to study at Stanford University, his parents’ alma mater.

At the time, Meggin was a sensible, agreeable child. She loved her horse and hated her red hair and freckles. She was scared and confused at the changes in her sister. She would withdraw quietly to her room during Annick’s outbursts. In the early days of her sister’s roaming, her parents told her: “We don’t know if Annick will come back alive.”

“My parents were very good in getting us to talk about it and be open and see it just as an illness and not something to be ashamed of,” Meggin said.

In high school, she began digging for answers. For a biochemistry class, she went to UCLA’s medical school library and looked up schizophrenia.

Her curiosity prompted her to major in psychology at USC, then study for her doctorate.

An idea began to brew.

At a psychology conference in summer of 1993, a researcher’s talk on genes and schizophrenia prompted Meggin to think about when her mother was pregnant with Annick.

Patsy’s blood type was A negative, while Annick’s was A positive. Patsy had asked psychiatrists if the “negative” vs. “positive” blood was the problem. (Meggin and John are negative.) They said no.

The difference nagged at Meggin, who wanted to examine its implications. She approached her dissertation advisor, Sarnoff Mednick, a renowned schizophrenia researcher.

“Meggin wanted to do this for months before I said, ‘OK,’ ” recalled Mednick, a coauthor of the study. “It was just too much of a long shot.”

Meggin started her search by digging through Danish medical records, available because her professor had used them in another study. (Denmark’s records are extremely complete and the population is relatively homogeneous). She looked at blood types and schizophrenia rates. She tossed out variables. A pattern began to emerge.

Eventually, Meggin found that a blood type difference between a pregnant woman and her fetus can trigger harmful antibodies from the mother that affect fetal brain development.

That complication now is preventable. Since 1968, expectant mothers have been able to take a drug that prevents them from producing the harmful antibodies.

But Meggin’s finding opens the door for researchers to study how other immune system complications could disrupt fetal brain development, experts said.

“Perhaps the most important clinical implication of [Meggin’s study] is that some forms of schizophrenia may be preventable,” wrote psychiatrist Richard Jed Wyatt of the National Institute of Mental Health, in an introduction to her paper.

The blood type difference alone is not the problem, said Meggin, who received her doctorate in psychology last August. Rather, the incompatibility, along with an unknown factor--such as a genetic predisposition to mental illness--can lead to schizophrenia.

“Maybe my children will be a second-generation [schizophrenic], or John’s children, I don’t know,” she said.

Meggin, who dotes on her niece, doesn’t have much time for baby-sitting since she sometimes works until midnight. A postdoctoral fellow at the University of Pennsylvania in Philadelphia, she keeps in close contact with her family.

In March, Meggin, visited Finland to continue her research on blood types and schizophrenia.

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Patsy and Hal’s lives veered from the brink of retirement about the same time that Meggin was deciding to devote herself to schizophrenia research. In 1995, the couple received the Warren Williams Award from the American Psychiatric Assn. for exceptional contributions to the field of mental illness.

“I think it’s a very natural thing that her sister’s illness gave Meggin the motivation to find out what is going on,” said Hal, 64, “for the same reason we got involved--what can we do for the children of the future?”

When Annick’s troubles began, the Hollisters volunteered to work for a year or two for the New York-based National Alliance for Research on Schizophrenia and Depression.

In 1989, the couple offered to start a nonprofit offshoot of the alliance, NARSAD Artworks. They never left.

They work six days a week at the organization’s drafty 1,500-square-foot warehouse in Brea. NARSAD Artworks reproduces and sells the creations of mentally ill artists, distributing millions of note cards, posters and calendars nationwide. The artists, including Annick, are paid commercial rates.

Even when she was very ill, Annick found solace in art, as she did when she was a child. Her paintings for NARSAD Artworks include a white cat in a sunny field of flowers, and a Picasso-style watercolor of two people sharing a kiss.

For her 2-year-old niece, Annick painted whimsical Winnie the Pooh scenes on a toy trunk, turning it into “a family heirloom,” her mother says.

Eight years ago, Annick’s life started to get back on track with the help of new antipsychotic medications. She is a part-time clerical volunteer at the Los Angeles Zoo.

Annick, who wears her hair in a hip-length braid, likes to talk, although her words are slurred from the ravages of mental illness. Her speech is tentative, her manner fragile. Her train of thought tends to drift.

She remembers the bad days.

“I was part of the ocean,” she explained, without elaborating.

On a recent afternoon, Annick stopped short when she caught a glimpse of a picture of herself at 16, before her illness was diagnosed.

“I was a beautiful young lady,” she murmured. “I’ve become aged.”

Her family is happy with her turnaround, which started with the help of the new antipsychotic medications Prolixin and Clozaril.

In 1988, Annick was so psychotic that the family did not invite her to John’s wedding. Meggin says that when she gets married someday, she wants Annick to be her bridesmaid.

Last month, Meggin stopped by to see Annick on her way to do some research at USC. Afterward, they said goodbye in front of the small cottage that Annick shares with a roommate. Annick caught Meggin’s hand and swung it playfully.

For a second, they giggled, two sisters together again.

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What Is Schizophrenia?

Schizophrenia is not, as was once widely believed, a case of multiple-personality disorder. A rundown on the condition:

* Schizophrenia is a severe mental illness characterized by inappropriate emotions, hallucinations and a disordered thought process.

* Some medical journals call it “the worst disease affecting mankind.”

* Disease strikes in late teens or early 20s.

* It affects about 2.5 million Americans, or about 1% of the population.

* A growing body of scientific evidence indicates that brain abnormalities, rather than social conditions, are the cause.

* In the last six years, a host of new antipsychotic drugs has shown great promise in helping schizophrenics make steady recoveries.

For more information: The National Alliance for Research on Schizophrenia and Depression, (516) 829-0091

Sources: World Book Encyclopedia, Times reports; Researched by RENEE TAWA / Los Angeles Times

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What Hollister Found

Meggin Hollister’s research gives the first indication of a link between a mother’s immune system and schizophrenia. What she discovered:

1. The problem starts with a blood-type difference between mother and fetus--for example, if fetus has positive blood type while mother has negative type.

2. Through a tearing of the placenta or another mechanism, fetal blood comes into contact with the mother’s blood.

3. Mother’s immune system launches response, producing harmful antibody capable of crossing placenta and reaching fetus.

4. Antibodies affect fetal brain development, possibly leading to schizophrenia.

Sources: Meggin Hollister, the Archives of General Psychiatry; Researched by RENEE TAWA / Los Angeles Times