A SMALL BUT growing chorus of scientists is becoming convinced that insulin is just as important to the brain as it is to the body. The body needs insulin to convert sugar in the bloodstream to energy. People whose bodies either don’t make enough insulin or don’t process it correctly develop Type 1 or Type 2 diabetes, which can lead to poor circulation, kidney failure, blindness, and death.

The role of insulin in the brain is less clear, but this much is certain: When brain cells are deprived of insulin, they die. Now researchers are discovering that a breakdown in insulin-processing in the brain plays a role in mental illnesses. Perhaps even a driving role. Dr Suzanne de la Monte, a neuropathologist at Rhode Island Hospital in Providence, believes that Alzheimer’s disease could be called “Type 3 diabetes”. And C. Anthony Altar, president of Maryland-based Psychiatric Genomics, refers to schizophrenia as “diabetes of the brain”.

Though researchers are still answering basic questions about insulin’s role in mental illness, the potential impact of their work is dramatic. Until now, research on the ravages of Alzheimer’s has centred mainly on the amyloid plaques that build up in the brain as the disease progresses, while scientists have focused on a breakdown in brain cell communication to explain schizophrenia, in which victims often become delusional and erratic as brain tissue dies.

If the insulin researchers are right, those problems could be secondary to a more fundamental breakdown in the way brain cells process insulin to generate energy and protect themselves against death.

Whether an insulin shortage “causes the disease, contributes to the disease, or it’s the brain’s response to injury we don’t know yet”, says Dr Jesse Roth, geriatrician-in-chief of the North Shore Long Island Jewish Health System, who has studied insulin’s role in the brain since the 1980s.

Doctors who treat Type 2 diabetes are already concerned about whether their patients are at greater risk of developing diseases of the brain later in life. Studies have shown that diabetic patients are at greater risk of Alzheimer’s, but researchers have assumed that diabetes is just one of several risk factors. Likewise, people with schizophrenia are at least twice as likely to develop Type 2 diabetes, but until now, scientists have attributed that to the unhealthy lifestyle of schizophrenics as well as the medications they take.

“We need to do the basic science, because we need to be sure,” says Dr C. Ronald Kahn, president of the Joslin Diabetes Center, who is concerned that the current Type 2 diabetes epidemic could foreshadow an explosion of mental illness.

Kahn’s research also suggests that insulin problems in the brain, in turn, may make people more vulnerable to Type 2 diabetes. Lab mice genetically modified to block insulin processing in the brain became obese and showed signs of diabetic insulin resistance. “If this is correct, the public health implications are huge,” he says.

Ironically, some doctors had latched onto insulin as a possible treatment for mental illness in the mid-20th century, when “insulin shock therapy” became popular as a last-ditch treatment for schizophrenia. The treatment pumped patients so full of the hormone that they would go into a diabetic coma.

While some schizophrenics, such as John F. Nash Jr, the mathematician portrayed in the movie A Beautiful Mind, showed improvement from the shock treatment, up to 10 percent of the patients died, and by the early 1960s, insulin therapy had gone onto the scrapheap of medical history.

FAREWELL TO ALL: Alzheimer’s claimed Ronald Reagan’s life in June 2004.

When Roth began his research for the National Institute of Health 25 years ago, most neurologists agreed that insulin played a negligible role in brain chemistry. Insulin levels in the brain were low compared with levels in the rest of the body, and the brain seemed to have limited need for the hormone.

But Roth’s team at NIH showed that brain cells possess insulin receptors to grab the hormone as it floated by and took pictures of insulin binding to receptors in rats’ brains. They argued that insulin played a complex role in brain cells, from cell repair to self-defence. Far from being a bit player in the brain, Roth suggested that insulin “has a very rich job description”.

When De la Monte started her insulin research in the early 1990s, the neuropathologist was amazed that few scientists had built on Roth’s work. She used a chemical treatment to drastically reduce insulin levels in the brains of rats and found that they developed Alzheimer’s symptoms, including large-scale cell death. She says, “Immediately I knew we had to stop everything we’re doing and focus on Alzheimer’s.”

In recent years, De la Monte’s lab has shown that the brain actually produces insulin itself rather than relying on insulin from the pancreas that circulates in the body. Last year, in a study of brain samples from 45 Alzheimer’s patients, De la Monte found that the number of insulin receptors in the frontal cortex, the centre of intellect, drops by 80 per cent in advanced cases of the disease, meaning that the cells don’t get the insulin they need to survive. “Insulin disappears early and dramatically in Alzheimer’s disease,” says De la Monte, who also teaches pathology at Brown University Medical School. “Many of the unexplained features of Alzheimer’s, such as cell death and tangles in the brain, appear to be linked to abnormalities in insulin signaling.”

Of course, other Alzheimer’s researchers say it’s too soon to say that insulin defects are the most important cause of the disease. Large-scale studies have also shown that high blood pressure, obesity, and cardiovascular disease put people at higher risk. “It is a real stretch to call Alzheimer’s disease Type 3 diabetes,” said Dr Hugh C. Hendrie, co-director of the Center for Alzheimer’s Disease and Related Neuropsychiatric Disorders at Indiana University.