Erasing the Line Between Mental and Physical Ills

When the fears first came upon him, Chris Hanson tried to outrun them. Night after night he sprinted through the streets and fields of his Iowa hometown until he was bone-thin and exhausted--but no less tormented.

Later, he envisioned himself as a general in charge of a demonic army. Or a raw egg poised in a half-shell, always in danger of spilling out.

From age 16, he was schizophrenic. But Hanson didn’t know that until he read it on a medical chart 18 years later--after serial hospitalizations, unrelenting drug regimens and two nearly successful suicide attempts.

“I wish it would be over sometimes--just stop it, you know?” said the 48-year-old Orange resident, whose words slur slightly as a result of the gunshot he fired under his chin 23 years ago.

“I just think . . . we’re a different type of human being,” he said of schizophrenics. “People think of us as an animal.”

Hanson has spent his life struggling with an illness categorized--often disparagingly--as “mental.” But schizophrenia, most experts now agree, is no less physical a disorder than diabetes or heart disease. Often, it is more devastating to patients and their families.

At last, the walls are crumbling--these spurious divisions between what aggrieves the human mind and what ails the brain. Neuro-imaging, drug discoveries and patients’ painful experiences are exposing these categories as flimsy constructions.

For schizophrenics like Hanson and for millions who suffer mental disorders, that brings some relief--and hope. There is comfort simply in knowing that signs of once-elusive diseases such as depression, obsessive-compulsive disorder and schizophrenia can be picked up on brain scans. Beyond that, the scans and other advances raise the possibility of successful treatments.

New techniques have “remarkably changed our consciousness . . . given us a whole new vista in thinking about the basic biology of the diseases and approaches to treatment,” federal researcher Daniel Weinberger told a public forum at Caltech last summer.

The findings do not suggest that biology is destiny. Rather, nature and nurture interact to shape the mind; the environment constantly tinkers with the physiology of the brain. Behavior is both an effect and a cause of cerebral changes.

Even as they open possibilities, the discoveries ignite debate over mental health treatment. Is it best to work from the inside out, with “super-pills” like Prozac? From the outside in, with so called “talk” therapy? Give a dose of both perhaps? Which should come first?

For economic as well as humanitarian reasons, it is important to get the answers right. About a fifth of American adults experience some form of disorder affecting emotions, thoughts, personality or behavior during the course of a year. About 3%--5 million adults--are considered severely mentally ill. Direct and indirect annual costs of mental disease, in the expense-wary era of managed care, approach $150 billion.

How mentally ill people are treated, of course, is not solely the purview of science; it is perhaps foremost a matter of politics and public perception. But science has a way of seeping into the popular consciousness.

Nudged along by research and a growing advocacy movement, Americans’ attitudes toward mental illness have shifted dramatically over the last 15 years. One sure sign is last month’s historic congressional vote to outlaw basic inequities between physical and mental health insurance coverage.

The law falls short of mentalhealth advocates’ hopes, but it “shattered a conceptual barrier,” said Laura Lee Hall, deputy director of policy and research for the National Alliance for the Mentally Ill. For patients and their families, “it is similar to Rosa Parks refusing to sit in the back of the bus.”

“This is clear progress,” said Dr. Steven Hyman, director of the National Institute of Mental Health. “But there is still a long way to go in getting people to understand that mental illnesses are real, they are diagnosable . . . and that we have, by and large, very effective treatments.”

The Great Mystery

Hanson never felt like a normal kid. He was immature, he says, uneven in his development. He was in a class for gifted students one year and in the slow learners group another. He didn’t have a lot of friends. Mostly he studied, played his oboe and worked on his parents’ farm.

Everything “went haywire” when he was 16, he says, after he took one of his mother’s diet pills. He was never the same. Thoughts kept repeating in his mind: “If I stop [running], I’ll die.” His parents sent him to a school for the mentally disturbed. There, he searched psychology books in hopes of discovering what had happened to him.

“I just knew, whatever it was, it was very bad,” he recalled. “I was always running on empty, like suddenly I was going to melt down. It’s like running out of life without running out of time.”

One of the great mysteries of schizophrenia--in which a person’s thoughts and emotions become unmoored from reality--is its seemingly sudden onset during late adolescence and early adulthood. Why should a young person, apparently without warning, begin communing with internal voices, conjuring up terrifying images or withdrawing into a private world?

The late, dramatic symptoms prompted speculation in the middle of this century that the disease resulted from cruel influences such as unstable mothers who drove their children to madness. Others described it as “a sane reaction to an insane world.”

Research, especially in the last decade, has suggested otherwise. Evidence has mounted that schizophrenia is fundamentally a brain disorder with roots in genetics and very early development.

In the beginning, its signs are deceptively subtle--but not, to discerning eyes, undetectable.

More than 40 years ago, through measurements she painstakingly plotted on graphs, UCLA professor emeritus Barbara Fish, then at New York’s Bellevue Hospital, noticed unusual traits in children born to schizophrenic mothers.

From infancy, many showed erratic motor and visual development--inexplicable surges and delays in their growth. Even normally steady skeletal growth was off--indicating “something was very fundamentally wrong,” said Fish, who published a summary of findings from her long-term study in 1992.

A few years ago, Emory University researchers in Atlanta inspected family home movies for clues. From their first months of life, children later diagnosed as schizophrenic expressed more discomfort, irritability and distress than their siblings. They also had more odd movements--jerking and writhing, for example.

“The bottom line is that some individuals appear to be vulnerable to schizophrenia due to brain abnormalities . . . present at birth,” concluded Emory psychology professor Elaine Walker.

Hormonal changes of early adulthood might trigger acute symptoms of the disease, she said. Use of drugs such as cocaine or amphetamines--which can produce temporary psychosis in anyone--can be a breaking point for schizophrenics.

Genes play a big role. An identical twin of a schizophrenic is about 50 times more likely to be schizophrenic than a member of the general population. But what one inherits is a significant vulnerability--whether it is expressed depends on life’s course.

One contributing factor is early brain damage, especially during the second trimester of fetal development. A mother’s bout with the flu, malnutrition, a torn placenta, insufficient prenatal care or other obstetrical complications all ratchet up risk.

Whatever the cause, the brains of schizophrenics end up mis-wired. UC Irvine researchers recently found that certain neurons, or brain cells, were scrambled in seven of 20 schizophrenics whose brains they autopsied. A structure called the cortical subplate, which guides formation of the cerebral cortex, apparently botched the job. (The cortex is the brain’s sheath of gray matter, where most of its higher functions take place.)

Although the subplate eventually self-destructs, traces left behind indicate that the neurons did not get where they were supposed to go, or didn’t form the right connections when they got there, said UC Irvine psychiatrist Steven G. Potkin, one of the study’s authors.

Other abnormalities show up in schizophrenic brains: larger ventricles (reservoirs of cerebral spinal fluid), malformations of the temporal lobe, including the hippocampus, and a smaller thalamus. The hippocampus, buried several inches deep behind the ear, is involved in learning and memory; the thalamus, at the brain’s core, is a sensory filter.

Recently, neuro-imaging maps of the brain’s use of energy have suggested that schizophrenics’ brains work differently as well. When solving abstract problems, such as categorizing a card by shape or color based on recent instructions, the frontal lobes of schizophrenics do not glow with activity as much as normal people’s do.

The prefrontal cortex is by no means the only structure involved. Schizophrenia can affect different parts of a circuit connecting the cortex, knots of gray matter called the basal ganglia, and the thalamus. That’s why schizophrenia often is described as a syndrome comprising several disorders rather than a single disease.

“There seems to be some deficit in how the different parts of the brain talk to each other . . . some abnormality of interconnections,” said Weinberger, a psychiatrist with the National Institute of Mental Health.

That can make the schizophrenic’s world a frightening place in which to dwell.

The patients’ perceptions ought not to be dismissed as imaginary. A neuro-imaging study last year by Cornell University and London researchers showed that the visual and auditory hallucinations of schizophrenics activate the parts of the brain used to perceive sights or process speech. They do apparently hear voices, and they do see things, even if others don’t.

Drugs are the first line of defense.

Most successful medications block activity of the brain chemical dopamine, thought to be out of balance in schizophrenics. However, these often carry discouraging side effects--freezing and shuffling similar to the symptoms of Parkinson’s disease, for instance. Not so with the acclaimed drug Clozapine--but that medication occasionally causes perilous bone marrow toxicity. Less risky compounds with the advantages of Clozapine are in various stages of development, including one approved by the FDA this month.

But non-drug approaches can also help. Patients relapse less often--and may even be able to reduce drug dosages--when coached in social and independent living skills, said UCLA psychiatrist Robert Liberman, who has studied the disorder for 30 years. Their brains, he says, can be retrained to cope better with stress.

“This lends a lot of optimism to the treatment process,” he said. “One isn’t relegated to using biological elements for what is a biological disorder--one can exploit the environment.”

‘Shake in the Mind’

When Joyce Cerrone was 9, her brother spooked her with tales of snakes and spiders. She took to meticulously checking for these invaders each night between her sheets and in her closets.

As a teenager, after the funeral of a family friend, she felt strangely itchy and unclean. She went home and took 14 showers, taking care each time to wash her hair and scrub underneath each nail.

The older she got, the worse the obsessions--and the more elaborate the protective rituals--became. Soon all it took was for someone to upset her. They’d become “contaminated” and she would go through hours cleansing herself and her home of their invisible filth. Her ex-husband, her parents, her siblings, her children’s schools, entire cities became contaminated. At the worst, she was housebound. She’d sleep on the floor when she got tired and resume scrubbing when she awoke.

“It’s almost easier when other people aren’t in your life,” said Cerrone, a 45-year-old Marina del Rey resident with two daughters. “It’s a pretty hard disease. You build yourself a prison that it’s hard to get out of.”

Not so long ago, obsessive-compulsive disorder (OCD) was considered a classic neurosis. The compelling internal commands and the desperate attempts to quiet them were linked to repressed conflicts over toilet training or sexuality.

But, as UCLA psychiatrist Jeffrey Schwartz recently told OCD patients, including Cerrone, at a support group session, it is more appropriate to consider the disease a “shake in the mind,” akin to Parkinson’s tremors. Both disorders are characterized by disruptions in the basal ganglia; one causes abnormal movements, the other abnormal thoughts.

In OCD, scientists have found a remarkable example of how drugs and behavioral therapy each can act on the biology of the brain to relieve its anguish.

Successful drug treatment and successful behavioral therapy produce essentially the same cerebral transformations, according to research published by Schwartz and Lewis Baxter, of UCLA and the University of Alabama.

PET scans show that the orbital cortex, at the underside of the brain’s prefrontal lobe, is overactive in OCD patients. It may act as an alarm system, activating a “worry circuit” including the caudate nucleus, a part of the basal ganglia that helps in switching gears from one thought to another; the cingulate gyrus, which wrenches the gut with dread, and the thalamus, which processes the body’s sensory inputs.

In OCD, according to Schwartz, these brain parts become “locked together” or “stuck in gear.”

They can become unstuck with Prozac, which enhances the effects of the chemical messenger serotonin, or with 10 weeks of behavioral therapy, studies by Schwartz and Baxter show.

The therapy involves systematically “relabeling” obsessive thoughts as disease symptoms and refocusing one’s attention elsewhere--on a hobby, for example.

“The beauty of being human, and not a rat or monkey, is that you don’t have to listen to your brain every single time” it sends a message, Schwartz said. The more you don’t listen, the less you are bothered by tyrannical obsessions.

PET pictures show that the caudate nucleus cools down when either pharmacological or psychological intervention works, presumably enabling the brain to switch gears.

This does not mean that drugs or therapy, or the two in combination, always work; even combining them doesn’t bring significant improvement up to 20% of the time. But the repertoire of promising treatment options is growing.

“It takes a whole lot of courage,” Cerrone said of the behavioral technique. At first, resisting the internal commands was about as appealing to her as jumping out of an airplane. But the terror subsided with practice, and she is convinced that it will never be as bad as it was. Someday, she hopes to go off medication entirely.

What causes this paralyzing “brain lock” in the first place? The answer still is unknown. But OCD researcher Susan Swedo and her team at the National Institute of Mental Health have some intriguing leads.

Swedo’s group has found a link between childhood strep throat and obsessive-compulsive symptoms or tic disorders.

In susceptible patients, antibodies attack the basal ganglia, causing OCD-like behaviors including excessive washing or germ phobias. Normally, these symptoms disappear with time. But, Swedo says, it’s possible that repeated infections--some scarcely noticed--may trigger OCD or the verbal tics in Tourette’s syndrome.

This is far from a full explanation for OCD--genes and other environmental triggers can be involved--but the discovery establishes one provocative link between brain diseases and neuropsychiatric illnesses. And it provides hope for early intervention: Well-timed treatments such as penicillin and gamma globulin can relieve behavioral symptoms.

“Even if trauma or a psychological cause is the stressor that triggers symptoms, it is not possible to give one OCD by being mean to them,” Swedo said “It is not caused by defective toilet training. This is a real neurobiological disease.”

Unmasking Depression

Nancy Gothier was wiped out. She had no hope, no interest in anything. She wanted to hide out, to lie down and sleep forever. Her concentration was gone, her memory dim. Even going to the market was an unbearable burden. She didn’t want to be here anymore.

One morning in the 1960s, she got out of bed, got dressed for work, did her makeup and her hair--then decided, almost matter-of-factly, on a solution. She got back in her nightgown and took every sleeping pill she had.

That time, her husband awakened and found her; the next time, it was her two young daughters. She spent nine years in and out of hospitals, all of that time misdiagnosed and improperly medicated as a schizophrenic.

“I got sick physically, I didn’t eat, I got very thin. . . . I didn’t know what was wrong with me. I knew I was very different from everybody else and that made it all the worse. I felt so unapproachable and freakish. I couldn’t understand why I couldn’t feel better because I wanted to so badly.”

Major depression--which is what afflicted Gothier--is not the same as “having the blues.” It is not a typical response to a bad day. It does not lift with a trip to the movies and doesn’t respond to the instruction “Snap out of it!”

Although often treatable, depression frequently is left to follow a grim course on the assumption it is a failure of will, best cured by a strong yank to the bootstraps.

Actually, it is a physical condition that can be as debilitating as coronary artery disease, and even more so than diabetes or arthritis. But its biology is not as well mapped out, partly because depression comes in different forms, or subtypes.

Steadily, though, brain scientists are working to unmask its complexities. Brain imaging highlights unusual activity in circuits involving the prefrontal cortex, the limbic regions underneath and those deep-seated knots of gray matter, the basal ganglia.

Activity in the prefrontal cortex is often muted, particularly on the left side. A team from Washington University in St. Louis found that a portion of the cingulate gyrus--a part of the cortex that helps regulate release of the brain messengers serotonin, norepinephrine and dopamine--is abnormally small, possibly leading to chemical imbalances.

The same team, and several others, have found hyperactivity in the amygdala, a tiny but powerful structure named, in Greek, for its likeness to the almond.

“The higher the activity . . . the greater the depression,” said researcher Wayne Drevets.

Antidepressant drugs suppress the amygdala--probably by acting on its rich supply of receptors for serotonin and norepinephrine, Drevets said.

The findings could help explain why depressed patients often have an oversupply of stress hormones in their spinal fluid and blood--and often suffer anxiety and panic.

The amygdala drives the body’s stress response, setting in motion a hormonal cascade that ends with secretion of cortisol in the bloodstream, Drevets said. Normally, cortisol release causes the brain to turn off the stress response, but for some reason--maybe a malfunction of the amygdala itself--this handy negative feedback function doesn’t work correctly in patients with depression.

The more often depression occurs, the more likely it is to recur--perhaps because neurons in the amygdala become oversensitized with time.

The process can begin early in life. Simply by separating rat pups from their mothers, researchers at Emory University altered their cortisol system into adulthood.

But it’s not all nurture, or the lack thereof. Heredity is heavily implicated in bipolar depression, in which moods swing between extreme lows and highs. In other depression types, the genetic component is more elusive: It seems that certain genes need to be activated by life’s slings and arrows.

The chemical defense often works. Two-thirds of patients will improve if treated with any antidepressant.

Yet even the champion drugs like Prozac, which selectively work on serotonin pathways, are not precision tools. Prozac acts on some 15 serotonin receptors, with widespread effects. How exactly does it soothe depression and OCD? Why does it sometimes dull sexual response? Is it safe to take indefinitely? These are open questions.

Psychotherapists, whether treating depression or other impairing illnesses, face their own set of daunting challenges. One is convincing skeptical employers and insurers that it is worth the time and money.

Still, many patients are inching toward optimism. For the first time, under federal law, they will receive basic protections against discriminatory lifetime and annual caps in insurance coverage.

And after years of misdiagnosis and misunderstanding, medical advances have made feeling better seem like an option.

Buoyed by her own improvement with medication, Gothier dared to ask her adult children how they had felt, years ago, when she tried to take her life.

“They said, ‘We thought you didn’t love us,’ ” she said, her voice catching. “So I said, ‘Guess what? I promise you I’ll never do that again.’ . . . Now I know that I’ll never be depressed for long, and I’ll feel good again.”

THE BRAIN: A WORK IN PROGESS / Even as they open possibilities, new discoveries ignite debate over mental health treatment.

THE NEW VISTA OF THOUGHT

New techniques have ‘remarkably changed our consciousness . . . given us a whole new vista in thinking about the basic biology of the diseases and approaches to treatment.’

--Daniel Weinberger, psychiatrist with the National Institute of Mental Health.

*

SEEKING UNDERSTANDING

‘There is still a long way to go in getting people to understand that mental illnesses are real, they are diagnosable . . . and that we have, by and large, very effective treatments.’

--Dr. Steven Hyman, director of the National Institute of Mental Health.

*

THE BOTTOM LINE

‘The bottom line is that some individuals appear to be vulnerable to schizophrenia due to brain abnormalities . . . present at birth.’

--Emory psychology professor Elaine Walker.

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Glossary

Depression: A psychiatric disorder characterized by a loss of interest in life and a lowered sense of well-being. In severe forms, it can result in loss of appetite, sleeping difficulties, fatigue, loss of concentration and suicidal thoughts.

Obsessive-compulsive disorder: A psychiatric disorder in which patients are troubled by persistent ideas that often push them to perform repetitive, or ritualized, tasks.

Schizophrenia: A disabling, usually chronic, mental illness in which a person’s thinking, emotions and behavior are severely disturbed. It is characterized by delusions, hallucinations, disorganized speech and behavior, and other psychotic symptoms.

Caudate nucleus: A part of the brain, near the core, that functions as the “automatic transmission” for thinking. It is believed to be overactive in patients with obsessive-compulsive disorder.

Serotonin: One of the brain’s chemical messengers, or neurotransmitters, with widespread effects thought to be involved in regulation of mood states including anxiety and depression. Prozac and other drugs prolong the presence of serotonin in the synapse, the space between neurons, enhancing the neurotransmitter’s effects.

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About This Series

Who are we? Where did we come from? While many scientists search for clues to these ultimate questions by probing the far reaches of the universe, others think the answers lie inside our own heads. Their probes are uncovering galaxies of neural cells, each twinkling with the brain’s life forces. As it orchestrates human behavior, this symphony of electrochemical communication may indeed constitute our very essence.

Sunday: The explosion of knowledge in the field of brain development, where researchers are finding that those first few years of life are far more critical than anyone had guessed.

Monday: New technology is uncovering the brain’s prominent role in emotions.

Today: Mental illness

Wednesday: Poised at what may be the last frontier of science, researchers are trying to discover the nature of human consciousness.

This series will be available on The Times’ Internet site beginning Wednesday at: https://www.latimes.com/thebrain

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Two Treatments, Similar Results

The right caudate nucleus of the brain functions like the automatic transmission in a car, in that it helps the brain “change gears” from one state to another. In patients with obsessive-compulsive disorder (OCD), the caudate is thought to be overactive, and the brain gets stuck in gear.

These PET scans of two OCD patients show how similar changes in the brain were obtained in one patient through medication, and in another, through therapy.

WITH MEDICATION (BEFORE/AFTER): Activity in right caudate nucleus shrinks in a patient treated with drug called a selective serotonin reuptake inhibitor (such as Prozac).

WITH THERAPY (BEFORE/AFTER): This OCD patient responded to medication-free, cognitive behavioral therapy. Again, activity decreases in right caudate nucleus.

Source: Dr. Jeffrey Schwartz, UCLA School of Medicine