Sophia Frangou, MD, PhD

Sophia Frangou, MD, PhD

Individuals whose siblings have bipolar disorder are at high risk for developing mood disorders themselves. However, siblings who remain psychiatrically healthy may have a natural ability to rewire their brains that compensates for their genetic risk. These findings, led by Sophia Frangou, MD, PhD, Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai, were published in the January 5, 2016, issue of Translational Psychiatry.

Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes fluctuations in patients’ mood, energy, activity levels, and the ability to carry out day-to-day tasks. Most of the risk (up to 80 percent) of developing bipolar disorder is genetic and can be traced to genes that affect brain function.

Studies show that close relatives of a person with bipolar disorder are up to ten times more likely than a typical person to present with a range of mood problems.

The new study examined patterns of brain connections in patients with bipolar disorder and their healthy resilient siblings, and then compared them to unrelated healthy individuals without a family history of the disorder. Siblings selected to participate in the study were in their mid-40s, an age when the chances of developing the disorder are very low.

Functional magnetic resonance imaging (fMRI) results revealed that compared to healthy unrelated individuals, patients with bipolar disorder and their resilient siblings showed similar brain abnormalities when asked to perform tasks that tap into brain functions known to be affected by bipolar disorder. However, the resilient siblings showed additional changes in brain wiring within these networks that were unique to them and, therefore, likely to represent adaptive rewiring that has helped them remain well.

“So far in the field of psychiatry we have focused on risk, and on brain changes that contribute to illness, instead of looking for brain changes that can be protective,” says Dr. Frangou. “The fact is the majority of people at high risk for bipolar disorder remain free of any psychiatric disorder. Recognizing the factors that promote resilience in the presence of significant genetic risk is very important as it shifts the focus from illness to well-being.”

The research suggests “that it is possible for some individuals to develop adaptive changes naturally, and we can promote these connectivity changes in other high-risk people,” Dr. Frangou says.

Ultimately, Dr. Frangou expects to develop an algorithm able to reveal the likelihood that a person with a high risk for developing bipolar disorder will actually develop it. She also wants to extend her research to include relatives of people with schizophrenia and to develop a computer-based cognitive training intervention to evaluate whether mental exercises can help promote resilience.

“Looking for biological mechanisms that can protect against illness opens up a completely new direction for developing new treatments,” says Dr. Frangou. “Our research should give people hope that even though mental illness runs in families, it is possible to beat the odds at the genetic lottery.”

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