New Day Dawns in Understanding Brain Disorders
Many researchers believe they stand on the brink of understanding a variety of brain-related disorders, ranging from depression and anxiety to Alzheimer’s disease and stroke.
Increasingly, psychiatrists are inching their patients off the couch and toward the test tube as treatment continues to become as much a function of better living through chemistry as talk therapy. From the laboratory comes new research on genes and nerve cells that changes doctors’ view of major mental and neurological diseases. From psychological studies comes new understanding of how moods and behavior can be explained by a wide variety of causes.
There is a growing awareness, says Steven Paul, acting director of the National Institute of Mental Health’s Intramural Research Program, “that psychiatric illnesses need to be treated with a combination of medications plus psychosocial interventions.”
The late 1980s brought major strides in understanding the biological and molecular basis of many brain disorders. There was the discovery of the gene marker for Huntington’s chorea--a debilitating neurological disease that often plunges its victims into mental problems. There were scans of the brain using positron emission spectroscopy. Suddenly researchers could see how parts of the brain begin shutting down in Alzheimer’s patients and how brain cells in schizophrenics are organized differently from those of people without the disease.
What has spurred the pace of this revolution in brain science is the marriage of molecular biology and genetics with brain research.
“This is the major direction that this field will begin taking in the next few years,” said Solomon Snyder of the Johns Hopkins Medical Institutions in Baltimore.
Brain and nerve cells signal each other in two ways: through electrical impulses and by the release of chemical substances called neurotransmitters. The quest to master these molecules will open the door to understanding how the brain works so that medical investigators can unravel the mysteries of memory, behavior and mental illness.
Neurotransmitters are released by cells and attach themselves to other cells at sites called receptors. Receptors are like a series of deadbolts on the cell’s surface. Each type of receptor has a particular configuration that can only be opened with the right key--a chemical substance that has the correct fit, be it a neurotransmitter or a drug that chemically resembles the right type of neurotransmitter. The correct fit--say by a molecule of dopamine attaching to a dopamine receptor--unlocks the function of that particular cell.
Ever since the first of these neurotransmitter receptors--one for opiates--was identified in 1973, the field has exploded. Today, several groups of researchers have gone a step further and now can clone the genes that dictate the shape of a neurotransmitter receptor.
By knowing the chemical structure of the receptors, researchers have begun to unravel how medications attach to nerve cells and exert their effects on the brain. Drugs to control depression, psychosis and anxiety--three of the major mental illnesses in the United States--act through these important receptors. So does L-Dopa, one of the medications used to control Parkinson’s disease.
The ability to identify and clone the genes that are responsible for important brain activities opens the door not just to understanding how brain cells work, but to fixing them when they go awry. “It has very practical consequences for medicine,” Snyder said. For example, it is now known that some anti-psychotic drugs work by attaching to dopamine two receptors.
“The point is that now we have done something that has historically been quite difficult to do,” said NIMH’s Paul. “Often we use drugs, sometimes for hundreds of years, before we know how they work. Now we are starting out in some instances to know almost exactly how they work.”
The rapid pace of gene research has also changed the medical approach to a number of brain disorders. The discovery of a gene marker for Huntington’s disease allows clinicians to determine in most cases whether an individual is at risk for the neurological disease years before symptoms appear.
Meanwhile, new imaging techniques are providing clearer windows into the brain’s inner workings. In addition to PET scans, the use of magnetic resonance imaging continues to grow. “People are looking at much greater detail at the changes in the structures of the brain,” said Paul. “The resolution is just fantastic.”
The new generation of brain scanners is called SPECT--for single photon emission tomography. PET and SPECT allow neuroscientists to examine the function as well as the anatomy of the brain. Already the tools are being used to explore such wide-ranging diseases as Alzheimer’s, panic disorders, schizophrenia and multiple-personality disorder.
“This is an area of great excitement,” Paul said.
Among the winners in the new brain science are the traditional mental illnesses. According to an ongoing epidemiological study by the NIMH, an estimated 15% of the U.S. population suffers from a serious enough mental disorder to merit treatment. But only a third or less actually receive help.
Depression is the most common mental illness, afflicting about 10 million Americans a year and costing an estimated $10 billion in medical costs and lost wages. Treatment has come a long way since rest, usually in an insane asylum, was prescribed for what doctors called melancholia.
Depression is where mood and feelings are mixed with chemicals and genes. Far worse than simply feeling sad, those who suffer from depression battle emotions of helplessness and hopelessness. They feel irritable and afraid, often lose their self-esteem and have difficulty sleeping, eating--sometimes functioning. In extreme forms, depression pushes patients into suicide.
Increasingly, mental illnesses such as depression are coming to be recognized as having genetic and biochemical components. Having one parent with certain forms of severe depression is no guarantee that a child will also suffer from depression, but it may increase the odds--which is why there is an active search for a faulty gene that might increase the vulnerability to depression.
A few years ago, researchers were convinced they had identified the gene for manic-depression in a group of Amish families. In 1989, however, that work was proven wrong. Nevertheless, there is still enough evidence that genes may be involved for researchers to continue their search.
Today, medications are the standard prescription for most forms of depression. A growing list of antidepressants are available for aiding the 5.4 million Americans who suffer from major depression. They can also help the nearly 6 million afflicted with dysthmia--a less-severe form.
Another drug--lithium--continues to be the treatment of choice for manic-depression. Lithium helps mute the severe mood swings that afflict the million Americans who have this form of depression. Today, estimates are that 80% of people with depression can be helped with a mix of psychotherapy and drug treatment.
At the same time, there is a growing acknowledgement of the nuances of mental illness, of the subtleties between various forms of depression and the potential different varieties of schizophrenia. All this is leading to ways of making a more precise diagnosis. “There has been a real sense of trying to make diagnostic entities more reliable in psychiatry,” said Richard Jed Wyatt, chief of the neuropsychiatry branch at NIMH.
Just as internal medicine 40 years ago came to recognize that pneumonia could be caused by a virus, a bacterium or a fungus, so psychiatrists now realize that the same mental illness may be produced by very different causes.
Depression, for example, can be traced to many factors--an inherited gene, a reaction to drugs, a response to a personal crisis, the loss of a job, the breakup of a marriage, a symptom of another illness such as Alzheimer’s or heart disease.
“I think that five or 10 years from now, treating depression will be much more specific,” Wyatt said. “These are not single entities; they are broad diagnostic groupings. Knowing that will allow us to pick them off one by one.”
