JUN 28, 2016

Rare But Serious Gene Mutations Linked to Bipolar Disorder

WRITTEN BY: Kara Marker

Bipolar disorder affects millions of Americans, and although it isn’t always the case, it can be very severe. In a monumental new study from Johns Hopkins Medicine, researchers uncovered 84 gene mutations through genetic sequencing that could potentially be associated with the most severe form of this mental illness, making great strides with understanding how this complicated disease is passed down through generations.

A multifaceted and chronic mental illness, bipolar disorder generally consists of fluctuating between deep depression and elated episodes, called “manic episodes.” The National Alliance on Mental Illness (NAMI) intentionally differentiates the high and low episodes that characterize bipolar disorder from what healthy individuals might simply consider a good or bad mood. Treatment for bipolar disorders varies depending on how severe an individual’s condition is. Below are a few options:

Mood stabilizers, antipsychotic medications, antidepressants
Psychotherapy
Electroconvulsive therapy
Self-management strategies and education

After recently publishing results using genetics sequencing to diagnose brain inflammation, Johns Hopkins research continues with a novel study incorporating next-generation genomic sequencing to read the genomes of family members with bipolar disorder. Eight families with a significant history of bipolar disorder were included in the study, with a total of 36 genomes sequenced.

The results of the genome sequences led the researchers to develop a list of 84 rare gene variations that seemed to be overexpressed in the same way among most if not all of the genomes sequenced. However, while attempting to confirm the role of these mutations in the causation of severe bipolar disorder, they found that the data was not “powerful enough” when the mutations were compared to 4,774 healthy people without bipolar disorder. The 84 gene mutations were found to be overexpressed in 3,541 people with bipolar disease in the same confirmative study, but the team is not yet convinced that these variations have a direct role in causing bipolar disorder.

This study is an important example of why, like in the Johns Hopkins study of brain disease diagnostics, it is important to have a database of known risk genes to compare results from large-scale genome sequencing projects. To acquire this data, DNA from a large amount of people with bipolar disorder will need to be gathered and analyzed. “It will take genetic data from at least several thousand more people with bipolar disorder to confirm that these rare mutations do in fact directly cause the disease,” said Fernando Goes, MD, from the Johns Hopkins University School of Medicine.

Goes and his team have worked with the Bipolar Sequencing Consortium to start working toward compiling the needed data as well as to look for potential collaborators to help the process move faster.

Goes’ study is unique to other bipolar genetic studies that normally focus on understanding common DNA mutations that have an insignificant effect individually but collectively play a large role in causing bipolar disorder. Goes’ study focused on the gene mutations that are rare but also potentially cause the most severe forms of the disorder when overexpressed.

This study also confirmed an important connection between bipolar disorder, autism, and schizophrenia by identifying shared genes that had been found in previous studies.

The team from Johns Hopkins continues to gather resources and collaborators every day, and hopefully soon there will be a reliable and efficient database of bipolar disorder gene variations with which researchers can compare their data from next-generation sequencing.

The study was recently published in JAMA Psychiatry.

Sources: Johns Hopkins Medicine, NAMI