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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.
Fresh insights from a recent study of the genetics and biology of bipolar disorder could improve the diagnosis and treatment of the debilitating condition.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.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.The gene that holds the instructions for making CPG2 is Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1).
In laboratory models, for instance, they sometimes observed synapse dysfunction with combined rather than single variants.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. The researchers began by examining postmortem brain tissue from various brain banks.The samples came from people who had received a diagnosis of bipolar disorder, or other psychiatric conditions that share some of its symptoms, such as schizophrenia or major depression.
They also examined samples from individuals who did not have any of these conditions. The examinations revealed that only brain tissue from people with bipolar disorder contained significantly less CPG2. The bipolar samples did not show lower levels of other proteins known to play a role in synaptic functions: only CPG2 was lower.
“Our findings,” the authors write, “show a specific correlation between low CPG2 levels and incidence of [bipolar disorder] that is not shared with schizophrenia or major depression patients.”
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