How do genetic differences affect the risk of bipolar disorder?

How do genetic differences affect the risk of bipolar disorder?

Fresh insights from a recent study of the genetics and biology of bipolar disorder could improve the diagnosis and treatment of the debilitating condition.

dna structure
A new study shows how specific genetic differences affect neural circuits and raise the risk of bipolar disorder as a result.

So concluded the scientists at the Picower Institute for Learning and Memory at Massachusetts Institute of Technology (MIT) in Cambridge who carried out the novel research.

In previous work, they had already shown that a protein called candidate plasticity gene 2 (CPG2) helps to regulate the strength of synapses in brain circuits. Synapses are the connectors through which nerve cells, or neurons, relay chemical signals to each other.

In the more recent research, the investigators found that the brains of people with bipolar disorder contained unusually low levels of CPG2.

They also linked specific variants in the gene for CPG2 to dysfunction in synapses. These same genetic differences happen to occur in people with bipolar disorder.

The team reports the findings in a paper that now features in the journal Molecular Psychiatry.

“It’s a rare situation,” says senior study author Elly Nedivi, who is a professor in the Biology and Brain and Cognitive Sciences departments at MIT, “where people have been able to link mutations genetically associated with increased risk of a mental health disorder to the underlying cellular dysfunction.”

“For bipolar disorder this might be the one and only,” she adds.

She and her colleagues are not suggesting that the gene variants that they uncovered actually cause bipolar disorder.

What they are proposing, however, is that having those particular genetic differences could make people more susceptible to bipolar disorder.

In laboratory models, for instance, they sometimes observed synapse dysfunction with combined rather than single variants.

Bipolar and role of CPG2 in synapses

According to the National Institute of Mental Health, around 4.4 percent of adults in the United States will have bipolar disorder at some point in their lives.

People with bipolar disorder experience episodes of mania and depression that bring on extreme shifts in mood, activity levels, and energy.

The episodes are much more severe than the “ups and downs” that affect most people. They can make it very difficult to carry out daily tasks, get along with people, study, and pursue a career.

Bipolar disorder is a major cause of disability and high rates of death by suicide. Drugs do not always work and not everyone with bipolar will experience complete recovery between episodes.

Prof. Nedivi and her team have been studying synapses for many years.

They discovered that CPG2 influences synaptic strength by helping to regulate the number of receptors for the chemical signals that pass between neurons.

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Low CPG2 tied to bipolar disorder

The gene that holds the instructions for making CPG2 is Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1).

On learning that studies had linked variants in SYNE1 to raised risk of bipolar disorder, the team decided to investigate the underlying biology in the light of their own findings about CPG2.


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