Bipolar Disorder Study Identifies Significant Genetic Differences in Brain Systems

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Research, believed to be the largest ever genetic study of the condition, compared DNA in people living with bipolar disorder and those without it and found significant differences in the DNA variations linked to the brain and nervous system’s ability to transmit information.

This could pave the way for further medication that might be effective in treating the mental health condition, which causes extreme mood swings, by targeting some of these genetic variations.

Research was conducted by the Bipolar Workgroup of the international Psychiatric Genomics Consortium (PGC), of which the Bipolar Disorder Research Network (BDRN), co-founded by the University of Worcester and Cardiff University, is a key member. The findings have now been published in the journal Nature Genetics.

Professor Lisa Jones, who leads the BDRN at the University of Worcester, said about the research: “The Bipolar Disorder Research Network (BDRN) is the largest contributor of bipolar participants to this landmark world-wide analysis and we are indebted to everyone who has volunteered to help with BDRN over the last 25 years. Our findings provide researchers with important information to consider for a wide range of follow-up studies, from the biological mechanisms of bipolar disorder to its definition and treatment options.”

Researchers studied over 7.5 million common variations in the DNA sequence in blood samples from almost 415,000 people, over 40,000 of whom have bipolar disorder. By comparing the DNA variations in people with and without bipolar disorder, the study identified variations that point to systems within the brain that are important for communication between neurons. Neurons are the cells responsible for carrying information through the brain and nervous system so that we can react to our environment.

Dr Arianna Di Florio, BDRN researcher at Cardiff University (BDRN co-founder), said: “DNA is the instruction manual your body uses to develop and function. Each person’s DNA varies slightly from everyone else’s and this is what makes us different. This research found more than double the number of DNA variations that influence one’s risk for the disorder since our last paper. We are therefore another step closer to understanding the neurobiology of bipolar disorder and will continue to focus on improving this in our future work.”

Researchers from more than 200 institutions all over the world collected the bipolar disorder DNA samples. More than 6,000 samples were from BDRN participants. BDRN is one of the largest and most established continuous bipolar disorder studies in the world.

Professor Andrew McQuillin, who headed the University College London arm of the study, added: “This study found DNA variations linked to bipolar disorder that are relevant in neuron communication and calcium signalling. This points to the possibility of repurposing drugs already used for the circulatory system for bipolar disorder treatments.”

The actual effectiveness of these drugs for bipolar disorder remains unknown however and requires further research before any recommendations can be made. Other possible genetic variations that might be targetable by drugs were identified and may be of interest for researchers going forward.

The study also found overlaps between the biology of bipolar disorder and that of other psychiatric disorders such as depression and schizophrenia and, to a lesser extent, that of sleep habits and alcohol and substance use.

BDRN and the PGC plan to build on this work with additional cases and analyses of the data.