Study Finds a Higher Risk of Bipolar Disorder in Patients with SYNE1 Gene Mutations

A new study from the Picower Institute for Learning and Memory at MIT found that people diagnosed with bipolar disorder have a smaller amount of protein known as CPG2 in their brains. The MIT study also identified how specific mutations of the SYNE1 gene could undermine the expression of CPG2 and appear to be correlated with a higher risk of bipolar disorder.

This is in line with other genome-wide association studies on neuropsychiatric disorders that identified a risk for bipolar disorder containing the SYNE1 gene, which encodes proteins including CPG2.

CPG2 is a brain-specific protein in excitatory postsynaptic sites where it regulates glutamate receptor internalization. In the study, the researchers identified significantly decreased levels of CPG2 protein levels in postmortem brain tissue from BD patients, compared to control subjects. However, the Picower Institute stated, “The researchers are not suggesting that the CPG2-related variations in SYNE1 are 'the cause' of bipolar disorder, but rather that they likely contribute significantly to susceptibility to the disease."

The study was led by Elly Nedivi, professor in MIT’s departments of Biology and Brain and Cognitive Science and according to Nedivi, “It’s a rare situation 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.”

This could potentially be game changing for the study of bipolar disorder, as the national comorbidity survey estimates 4.4% of US adults will experience some form of bipolar disorder during their lifetime. The authors ultimately concluded, “Few GWAS hits in human genetics for neuropsychiatric disorders to date have afforded such mechanistic clues. Further, the potential for genetic distinction of susceptibility to BD from other neuropsychiatric disorders with overlapping clinical traits holds promise for improved diagnostics and treatment of this devastating illness."