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Scientists have tried to ascertain if schizophrenia is related to a shrinkage in brain size.

News from the Harvard Medical School research community.

Mental health

Brain Size and Signal Decline with Advance of Schizophrenia.

Dean Salisbury, HMS associate professor of psychiatry at McLean Hospital, and Robert McCarley, HMS professor of psychiatry at the VA Boston Healthcare System, have found both structural and functional evidence that schizophrenia is a progressive disorder, according to their report in the May Archives of General Psychiatry. "This changes our view of the disorder ...and could possibly lead to a therapy that could arrest the course of schizophrenia," said McCarley.

Researchers have debated whether or not schizophrenia, which attacks both the frontal and temporal lobes of the brain, is set at birth or develops over time. Previous magnetic resonance imaging (MRI) studies of schizophrenics showed no progressive changes in the brain, but a few studies near first hospitalisation did show a change in brain size. Still, the results were controversial-stronger evidence was needed.

What researchers sought to uncover was a decrease in brain size that corresponded to a loss of brain function. Salisbury and McCarley found just that - a tight correlation between a brain wave called mismatch negativity (MMN) and the volume of the Heschl gyrus, a section of the temporal lobes.

MMN brain waves, caused by auditory cues, are tested by playing a series of identical beeps, with an occasional "oddball" beep thrown in. The brain automatically responds to this difference by producing an MMN, which originates from the Heschl gyrus.

In a series of three experiments spanning 18 months, McCarley and Salisbury found that schizophrenics' MMN waves were initially normal, but quickly diminished over time. In one test group, 14 out of 16 schizophrenia patients displayed an MMN decline over time, and in an additional test, 11 out of 11 test subjects showed a combined decrease in Heschl gyrus volume and MMN response.

While the sample sizes were relatively small, the researchers noted that long-term studies with the psychiatrically ill can be difficult - half of their subjects never returned for further tests. However, McCarley and Salisbury are following up with another study of new patients as a replication sample.

Not only does the study give hope of ending the onslaught of schizophrenia, it provides a tool to monitor the process. "Drugs that try to halt the shrinkage [of the brain] can be developed, and we can use the MMN to track that," said Salisbury.

Gregory Light, an assistant professor of psychiatry at the University of California, San Diego, who is not an author on the study, believes the work is groundbreaking: "It's really a substantial contribution to the science of understanding schizophrenia," he said.

Epidemiology

Women aged 50-59 who took oestrogen show a reduced risk of coronary plaque buildup.

A new study from the Women's Health Initiative (WHI) has evaluated, for the first time in a randomised trial, the relationship between oestrogen therapy and coronary artery calcium in young postmenopausal women. JoAnn Manson, MD, from Brigham and Women's Hospital (BWH) and colleagues found that oestrogen therapy in women aged 50-59 is related to lower coronary artery calcium, a marker for plaque blockage in the coronary arteries and a predictor of future risk of heart attack. These findings were published in the June 21, 2007 issue of the New England Journal of Medicine.

"These findings lend further support to the theory that oestrogen may slow early stages of plaque buildup and lead to less hardening of the arteries supplying blood flow to the heart," said Manson, lead author of the study and chief of Preventive Medicine at BWH. "These results, together with previous WHI findings about lower rates of coronary bypass surgery and angioplasty for younger women who take oestrogen, provide reassurance for recently menopausal women who are considering oestrogen therapy for the short-term treatment of menopausal symptoms," added Manson, who is also one of the principal investigators of the WHI.

Coronary artery calcium was measured by cardiac computed tomography (CT scans) in 1064 women who were aged 50-59 years and randomly assigned to oestrogen-alone therapy (conjugated equine estrogens, 0.625 mg/d) or to placebo at the start of the WHI trial. After an average of 7.4 years of treatment, the women receiving oestrogen were 30-40% less likely to have severe coronary artery calcium than women receiving placebo. Among women who were taking their study medications regularly, women receiving oestrogen had a 60% lower risk of severe coronary calcium. These risk reductions were statistically significant.

The authors caution, however, that the new study should not be interpreted to mean that women should take oestrogen to protect their hearts and stress that more research is needed to evaluate the effects of oestrogen in younger women.

"Although these findings indicate that oestrogen therapy in younger menopausal women is related to less plaque in the arteries supplying the heart, this does not mean that oestrogen should be taken for the express purpose of preventing cardiovascular disease," concluded Manson, who is also a professor of medicine at Harvard Medical School and author of Hot Flashes, Hormones & Your Health. "Oestrogen is known to have other risks and should be used only for the treatment of menopausal symptoms at the lowest dose for the shortest duration necessary," she added.

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