Can we escape from our DNA? Evidence in recent years has led psychiatrists to conclude that bipolar disorder—a mental health disorder characterized by abnormal shifts in mood and energy level—has genetic roots, a notion that could lead us to believe it is unavoidable for those carrying the relevant genes. But new research suggests that our brains may be able to overcome the genetic pull, and even allow those at high risk for the condition to avoid it completely.

The clue that some hidden mechanism enables people to overcome a genetic predisposition to the condition came from siblings. Brothers and sisters of people with bipolar disorder are up to 4 times more likely to develop the condition compared to the general population. Researcher have not yet identified a bipolar gene, as this figure is based on correlation, not causation. In addition, most research suggests bipolar disorder is likely due to a combination of several genes rather than a single one. Still, these results suggest that the condition is inherited, with siblings of diagnosed patients at the greatest risk. And yet not all siblings of people with bipolar disorder are themselves bipolar.  

Researchers from the Icahn School of Medicine at Mount Sinai Hospital, in New York, wanted to understand why. They hypothesized that the difference between affected and unaffected siblings was not environmental because brothers and sisters are usually exposed to similar life experiences. To find other underlying distinctions, they turned to imaging diagnostics that allow scientists to look directly inside the brain. Using functional magnetic resonance imaging (fMRI), they studied 78 bipolar patients, in addition to 64 of their unaffected siblings and 41 non-related controls who also did not have the disorder.

The images showed striking differences among unaffected siblings. According to the study, published in the American Journal of Psychiatry, siblings of bipolar patients who had the genetic evidence of brain abnormality associated with bipolar disorder, but were not bipolar, showed hyperactivity in the default mode network (DMN) in their brains. According to a press release on the recent discovery, the DMN is a network of interacting brain regions known to have activity highly correlated with each other and distinct from other networks in the brain.

This DMN hyperactivity was unique to the unaffected siblings. The researchers concluded that the hyper-connectivity in the DMN area of their brains enabled them to resist bipolar disorder, despite the condition already being mapped out in their genes.

“We do not know why some people at high risk become sick and why some remain well,” study researcher Sophia Frangou told Medical Daily in an email. “We know that the relatives of patients are very similar to patients in terms of genetic risk load but we think we have overlooked genes related to resilience that may differentiate those who convert to disease from those who stay away.”

According to the National Institutes of Health, bipolar disorder is a brain condition that causes unusual shifts in mood, energy, and activity levels. Patients are often unable to carry out daily tasks. Today, bipolar disorder affects around 2.9 percent of the U.S. adult population, the National Alliance on Mental Illness reports.

More research is needed to understand why some siblings of bipolar patients show DMN hyperactivity and others do not, including whether another genetic code may be at play. “We want to understand possible genetic contributors to resilience and we want to test ways of re-training the brain to adapt a more healthy functional configuration,” Frangou told Medical Daily.

Researchers hope that such advances could lead to more effective bipolar disorder treatments and prevention methods. The next step is determining whether the brain resilience observed in this study can be prompted where it does not already occur naturally, and perhaps even further enhanced in those who have it.

Mount Sinai researchers are currently exploring ways to re-train brains using cognitive computer basic training. Although it's too soon for results, the researchers are hopeful - if psychology has taught us anything, it's that the human mind is far more resilient than we might imagine.

Source: Frangou S, et al.American Journal of Psychiatry. 2017