Schizophrenia typically runs a far nastier course in men than in women; psychiatrists have long known that. Women tend to be struck by the disease later, they are less likely to be totally disabled, and their symptoms shade toward more easily treated delusions and hallucinations. They also respond more readily to medication.
Now a new Hopkins study suggests that basic differences between men and women in the way the disease rearranges the brain may be responsible. A report of the work appears in the March American Journal of Psychiatry.
The research focuses on a part of the cerebral cortex essential for attention and perception, called the inferior parietal lobule, or IPL. Working with the rest of the brain, the IPL translates sensory information such as touch, smell and vision into a sensible "map" of a person's world at any moment, says psychiatrist Godfrey Pearlson, who led the study.
The Hopkins scientists found that the overall IPL is smaller in people with schizophrenia. But they also report that in men with schizophrenia, the IPL is "built backward" from both women with the disease and people without schizophrenia.
"In normal men," Pearlson says, "the IPL on the left half of the brain is significantly larger than the right. But in men with schizophrenia, that pattern is reversed. This abnormality in a brain region that helps 'map reality' may account for the symptoms of distorted reality we see in schizophrenic patients."
Earlier work by the group showed that in normal women the IPL tends to be slightly larger in the right half of the brain than in the left. The right IPL, Pearlson says, probably governs the ability to sense relationships between body parts and the awareness of a person's own affect or feelings. The left is more involved in perception, such as judging how fast something moves or estimating time.
In the current study, researchers compared MRI brain scans of 30 men and women suffering from schizophrenia with 30 closely matched people without the disease. New computer software created by Hopkins psychiatrist Patrick Barta let them compare overall IPL volume by gender and by side of the brain. Scientists highlight the IPL by "painting" it in on computer images of each subject's brain. Then the software calculates a highly accurate volume.
IPL volume in men with schizophrenia was, on average, 16 percent smaller than in normal men. Also, the volume of left and right sides is proportionately reversed from normal.
"There's a striking interaction between gender and the illness," Pearlson says. "Since men and women have different brains, the disease naturally expresses itself differently. Women's brains are apparently better protected from whatever schizophrenia does."
The study adds to growing evidence that schizophrenia begins well before birth, during fetal development. "It's likely," Pearlson says, "that something goes awry with the way neurons migrate to the IPL and other brain regions, or with how they form connections."
Schizophrenia as a disease has been notoriously hard to pin down, Pearlson says. "It's likely more than one illness," he says, "but no one can figure [out] how to subdivide it. Classically, it's defined by symptoms--hallucinations, delusions, disordered thoughts--and a decline in social participation, but other diseases can have elements of that, too."
The Hopkins work is part of an effort to discover distinct, measurable abnormalities in the brain. The team has focused on a circuit in the brain that connects areas long thought abnormal in schizophrenia. These include parts of the prefrontal cortex and Wernicke's region, an important speech and language area. The Hopkins group earlier showed that Wernicke's region is also "built backward" in men with schizophrenia, resulting, they think, in the voices people with schizophrenia often report hearing.
In women, schizophrenia appears nearly 10 years later than in men. "That means it's less disabling," Pearlson says. Women also have fewer of what psychiatrists call "deficit symptoms."
"People with deficit symptoms are missing whatever helps us get up in the morning and come to work, learn new things, be goal-directed and have enthusiasm," he says. "It's a lack of directed energy."
Women's milder form of schizophrenia, says Pearlson, often lets them function socially in spite of the disease.
Melissa Frederikse helped with the study. Elizabeth Aylward, of the University of Washington, Seattle, and Tonmoy Sharma, of the Institute of Psychiatry in London, also participated.