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Mental Illness is no myth

By Tom Siegfried and Sue Goetinck

Mental illness is no myth.

It is a medical malady no less than heart disease or diabetes. It's as real as cancer and much more common. It strikes the young and the old, the right and the poor - some sort of mental disorder afflicts more than one in five Americans in the course of a lifetime.

It goes by many names - schizophrenia, major depression, bipolar disorder are just a few. Such labels reflect distinct illnesses but also conceal many common features. For "mental" illnesses are all, at root, disorders of thought or emotion, stemming from physical problems - the biological equivalent of faulty wiring - in the brain.

100 billion cells

To be sure, the wiring of the brain is more complicated than an ordinary electrical circuit or even a micro-computer chip. The mind's method of interoffice messaging includes both chemical and electrical signals. Each nerve cell has communication links too thousands of others, and any one cell is simultaneously a part of many different signaling circuits. Tracing all the connections of even one cell is a task too complex to imagine, and the human brain contains 100 billion such cells.

"Understanding the normal function of the human brain - and what goes wrong in the production of serious mental illness - may be the most difficult and complex activity that human beings have ever undertaken," says Steven Hyman, director of the National Institute of Mental Health.

Biology gone bad

Still, science has made substantial progress in the last half-century. Before the 1950s, mental illness was not a part of mainstream medicine. Now volumes of evidence attest to the way the biology of the brain goes awry in mental disorders. The chemistry at nerve cell junctions, the metabolism in different brain regions and subtle anatomical anomalies all point to mental illness as biology gone bad.

In some cases, the miswiring may begin even before birth, as nerve cells fail to find their proper place in fetal development. In other cases, chemical malfunctions may short-circuit initially normal nerve cell wiring. Since genes produce the chemicals, they are strongly implicated in most major mental disorders, but outside influences are no doubt at work as well. Traumatic experiences at an early age may predispose a child to depression later in life, for example.

Sorting out the ways the brain's biology goes bad is almost as complex as the brain itself. The American Psychiatric Association's 900-page diagnostic manual lists hundreds of "mental disorders," ranging from schizophrenia to insomnia. But most experts agree on a few "major mental illnesses" that seriously impair the thoughts, feelings or behavior of millions of Americans. For the most part the major disorders fall into three broad categories: schizophrenia and related disorders, mood disorders such as major depression and bipolar disorder (manic depression), and anxiety disorders including obsessive compulsive disorder and panic disorder.

Schizophrenia

Commonly - but incorrectly - thought of as split personality, schizophrenia is a serious and complicated disorder. The "split" is a disconnection between the mind and reality. Schizophrenia is recognized in cultures around the world, and it seems to strike roughly one percent of the population just about anywhere.

"It's a terrible disease and a major public health problem," says William Carpenter, director of the Maryland Psychiatric Research Center.

Victims of schizophrenia suffer serious psychotic symptoms: delusions (such as false fears of persecution) and hallucinations (such as hearing voices). Disordered thoughts, incoherent speech, social withdrawal and inability to pay attention are common features among schizophrenia's victims. Not all patients exhibit all symptoms, and many experts believe "schizophrenia" is an umbrella label for a whole set of diseases. In any event, schizophrenia is not a simple, single defect, but a disorder affecting more than one part of the brain.

"We think that different parts of the brain may be involved in different aspects of the illness," says Carol Tamminga, a schizophrenia researcher at the University of Maryland.

Until the discovery in the 1950s of drugs that treat it, schizophrenia remained essentially outside the realm of biology and medicine.

"Very few people took the idea that schizophrenia was a biological illness very seriously until it was discovered that this illness could respond dramatically to drugs," says John Csermansky of Washington University in St. Louis.

Still, the physical problems were not obvious. Only in recent years have modern technologies begun to isolate some critical, if slight, abnormalities in the brain.

"Whatever the anatomical change in schizophrenia, it's a very small one," says Daniel Weinberger of the NIMH. "This is not a stroke...this is not a massive failure of brain development - this is a subtle, subtle defect."

Among the best tools for identifying subtle brain flaws are brain scanners, able to create images showing fine points of brain anatomy or the flow of blood in different brain regions. Modern brain scans have shown that when one of two identical twins has schizophrenia, brain cavities call ventricles are slightly smaller in the normal twin.

Another difference has been found by Nancy Andreasen of the University of Iowa and colleagues. Their imaging studies show that the thalamus, a control center for routing signals to and from various parts of the brain, is smaller than normal in the brains of schizophrenia patients. A malfunctioning thalamus could contribute to the unfiltered flood of sensory stimulation that schizophrenia patients experience in hallucinations and delusions.

Dramatic new evidence of the inner workings of a brain with schizophrenia was published last November in the journal "Nature" by scientists in England and Cornell Medical Center in New York City. Their scans showed several brain regions to be highly active during hallucinations. False voices activated parts of the brain normally used in understanding speech; visual hallucinations in one of the patients showed activity in brain regions specialized for visual perception.

Brain scans also show that the schizophrenic brain doesn't perform thinking tasks as well as, or in the same way as, normal brains. During some complicated thinking tasks, such as sorting cards containing different symbols, the frontal cortex works harder in normal brains and the areas around the hippocampus in the temporal lobe work less. The pattern in schizophrenia patients is the opposite.

In other mental tasks, involving recognition of sounds, the frontal parts of the brain are underactive in schizophrenia patients, said Tamminga. Another region of the brain normally activated by such tasks - the cingulate cortex - is also active in schizophrenia patients, but at the wrong time in the course of the task. The cingulate cortex, part of the emotion-related limbic system, is believed to play an important role in the brain's ability to pay attention to stimuli.

Other schizophreniza-related anatomical differences suggesting a developmental problem have been detected in the planum temporale, a brain area involved in generating and understanding language. That region is normally larger on the left side of the brain than the right in right-hand people, but in schizophrenia patients the right side was larger, researchers from John Hopkins University School of Medicine reported last year in the "American Journal of Psychiatry."

Mood disorders

Mood disorders are much more common. Major depression affects about 5 percent of the population at any one time, and over the course of a lifetime 17 percent of the population experiences a major depressive episode, a 1994 study published in the "American Journal of Psychiatry" found.

"Major depression is a general category that probably includes several types of illness," says Wayne Drevets, a psychiatrist at Washington University in St. Louis. "There's a lot about depression we just don't know."

In about 1 percent of the population, depressive episodes alternate with a euphoric mood known as mania, marked by feelings of grandiosity or irritability. Popularly known as manic depression, this cycling between highs and lows is technically labeled bipolar disorder, reflecting its two extremes of mood. Recently psychiatrists have recognized a bipolar type 2, in which the manic state is not as extreme as in full-scale manic depression.

Clues to the biology of mood disorders have stemmed mainly from the drugs used to treat them. Manic depression is most commonly treated with compounds containing the element lithium. Most drugs for major depression affect the brain chemicals serotonin or norepinephrine.

Prozac, for example, attacks depression by blocking the molecules that clean serotonin out of the nerve cell connections known as synapses. That leaves more serotonin around, leading ultimately to an improved mood.

But the delay in the beneficial effects of Prozac and similar drugs - they can take a couple of weeks to work - suggests that depression is more complicated than merely a lack of serotonin in synapses.

Manic depression is even more difficult to understand. The evidence suggests that lithium operates inside the cell, perhaps affecting the internal cell molecules called G proteins. G proteins are key players in the cellular messaging systems that tell genes what chemicals to produce.

Drevets and colleagues have shown, for example, that depressed patients have abnormally high blood flow in the amygdala, a brain region important for emotional behavior.

Anxiety disorders

Major depression often accompanies another major group of mental illness, the anxiety disorder, among which the most prominent are panic disorder and obsessive-compulsive disorder.

In panic disorder, more than half the victims also suffer from major depression. Panic disorder itself is marked by recurring panic attacks - episodes of intense fear or terror accompanied by shortness of breath, chest pain or choking sensations. Panic disorder is not rare; worldwide studies estimate that 1.5 to 3.5 percent of the population can be affected over a lifetime.

Obsessive-compulsive disorder, or OCD, is marked by recurring concerns or doubts that intrude on normal life, or repetitive actions (compulsions) such as washing hands over and over again.

Not much is known about the causes of OCD, said Gerry Nestadt, a psychiatrist at Johns Hopkins Medical School.

There is evidence suggesting that in some cases of OCD, infection with the bacteria "Streptococcus" may be a contributing cause. Likewise, sometimes people with Huntington's disease or people that suffer a stroke or other brain injury can develop OCD symptoms. Use of certain drugs, such as amphetamines, can also lead to OCD, Nestadt said.

"What's going to help patients," said Pearlson of Johns Hopkins, "is integrating a lot of information from a lot of different areas of science."

©1996, Dallas Morning News

Modified December 25, 2002