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Brain connectivity changes may divert genetic risk for bipolar disorder

Unaffected siblings of individuals with bipolar disorder exhibited hyperconnectivity within the affect processing network, suggesting adaptive plasticity that allowed for compensatory changes, according to researchers.

“There is a strong genetic contribution to the etiology of [bipolar disorder], with estimated heritability between 60% and 85%. The genetic architecture of [bipolar disorder] is complex and probably polygenic. As patients with [bipolar disorder] and their unaffected relatives are likely to share some susceptibility genes, shared neuroimaging abnormalities are considered genetically driven markers of risk,” the researchers wrote.

Researchers used functional MRI to map brain connectivity patterns in individuals with bipolar disorder (n= 41), their siblings without bipolar disorder (n = 25) and unrelated healthy individuals (n = 46). During brain scans, study participants performed an emotional and nonemotional task that activated brain functions known to be affected by bipolar disorder.

Individuals with bipolar disorder and their siblings exhibited similar increases in frontolimbic connectivity during facial affect processing. However, unaffected siblings exhibited additional adaptive hyperconnectivity in the ventral visual stream.

During working memory processing, individuals with bipolar disorder exhibited widespread hypoconnectivity within the corresponding network, while unaffected siblings exhibited working memory network connectivity similar to that of controls.

“The ability of the siblings to rewire their brain networks means they have adaptive neuroplasticity that may help them avoid the disease even though they still carry the genetic scar of bipolar disorder when they process emotional information” study researcher Sophia Frangou, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York City, said in a press release. “A family history remains the greatest risk factor for developing bipolar disorder and while we often focus on risk, we may forget that the majority of those who fall into this category remain well. Looking for biological mechanisms that can protect against illness opens up a completely new direction for developing new treatments. Our research should give people hope that even though mental illness runs in families, it is possible to beat the odds at the genetic lottery.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.