One of the many puzzling characteristics of schizophrenia is that men generally suffer from the mental illness more severely than do women. Symptoms appear in males years before they do in women, and men overall are less responsive to medication. Now, recent imaging studies in a Johns Hopkins lab suggest that the way schizophrenia shapes the brains of men and women may underlie these gender differences.

In a healthy male, the left IPL is larger than the right.

Researchers led by psychiatrist Godfrey Pearlson focused on a part of the cerebral cortex called the inferior parietal lobule (IPL)--a sort of neural crossroads where pathways from many different brain structures converge. Each hemisphere of the brain contains an IPL. On the left side, the IPL is involved in visual perception and spatial relationships, such as gauging how fast a ball is moving. On the right side, the IPL governs a person's understanding of where each body part is in relation to another, a skill that is used in rock climbing or ballet, for example. The right IPL also comes into play in judging how another person feels by reading his or her facial expression or body posture.

In a previous study involving healthy volunteers, Pearlson and his colleagues found that men have a larger IPL than women (even after the volumes were adjusted for the relatively larger size of men) and that their left IPL is larger than their right. In contrast, healthy women had a reverse asymmetry: their right IPL was slightly larger than their left.

In the recent study, the researchers compared MRI brain scans of 30 schizophrenic men and women with scans from 30 healthy closely matched volunteers. They used a software program created by Hopkins psychiatrist and biomedical engineer Patrick Barta that uses MRI data to calculate IPL volume.

The results showed that schizophrenic men have a reversed asymmetry in the IPL, compared to healthy men. Their right IPL is larger than their left. Further, the overall size of the IPL of schizophrenic men is 16 percent smaller than it is in healthy men. Women with schizophrenia did not show significant differences in IPL size or asymmetry compared to healthy women.

The gender differences in IPL size and asymmetry could underlie clinical differences seen in men and women with schizophrenia, say the researchers, who reported their recent findings in the March issue of the American Journal of Psychiatry. Men who have schizophrenia generally begin showing signs of the illness between ages 15 and 20, compared to ages 20 to 25 for women. Likewise, "men have more subtle neurological abnormalities," says Pearlson. "They have more deficit symptoms such as a lack of will and directed energy. They [have difficulty] planning, completing things, or making decisions."

Although schizophrenia is best known for its hallucinations and delusions, those symptoms are often easier to treat than the broader, subtler deficits. As a result, women schizophrenics are more likely to marry, hold a job, and live relatively normal lives. But schizophrenic men often have symptoms that persist, and they tend to have more personal troubles such as being unemployed or homeless, Pearlson says.

"There is probably something in the whole circuit of which the IPL is part that gets miswired in schizophrenia," says Pearlson, who with his colleagues has identified other anatomical differences in the brains of schizophrenics. Understanding such differences, says Pearlson, could lead to interventions for delaying the onset or diminishing the severity of schizophrenia in people who are at risk, he says.

The IPL develops relatively late in adolescence or in early adulthood, notes Pearlson. "Because the brain is so plastic, if we could identify people at risk for schizophrenia, and give them some cognitive training, perhaps we could strengthen other areas, which could compensate for deficits in the IPL." Currently, however, he adds, "that is a highly hypothetical possibility."
--MH

source: John Hopkins Medical School, 2000