Naturally occurring changes in brain wiring can help patients at high genetic risk of developing bipolar disorder avert the onset of the illness, according to a new study led by researchers at the Icahn School of Medicine at Mount Sinai and published online today in the journal Translational Psychiatry. The study’s findings open up new avenues for researchers to explore ways the brain can prevent disease expression, also known as resilience, with the hope of developing better treatments.
Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes fluctuations in patients’ mood, energy, activity levels and the ability to carry out day-to-day tasks. Bipolar disorder is highly heritable, meaning that people with a parent or sibling with bipolar disorder have a much greater risk of developing the illness, compared with individuals with no family history.
Researchers used functional magnetic resonance imaging (MRI) to map the connectivity patterns in the brains of three groups: patients with bipolar disorder, their siblings who did not develop the illness (resilient siblings), and unrelated healthy individuals. While having their brains scanned, each participant was asked to perform an emotional and a non-emotional task that taps into two different aspects of brain function known to be affected by bipolar disorder. The resilient siblings and the patients showed similar abnormalities in the connectivity of brain networks involved in emotional processing. However, the resilient siblings showed additional changes in brain wiring within these networks.
“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,” said Sophia Frangou, MD, PhD, Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and lead author of the study. Dr. Frangou’s ongoing research uses neuroimaging to study how differences in brain wiring can either increase or decrease the likelihood of developing mental health problems.
“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,” said Dr. Frangou. “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.”
Funding: The study was supported by awards from the National Institute of Mental Health and the Brain & Behavior Research Foundation. Additional collaborators include researchers from King’s College London and Imperial College London, UK.
Source: Sasha Walek – Mount Sinai Hospital
Image Source: The image is in the public domain
Original Research: Full open access research for “Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder” by D Dima, R E Roberts and S Frangou in Translational Psychiatry. Published online January 5 2016 doi:10.1038/tp.2015.193
Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder
Bipolar disorder (BD) is characterized by emotional dysregulation and cognitive deficits associated with abnormal connectivity between subcortical—primarily emotional processing regions—and prefrontal regulatory areas. Given the significant contribution of genetic factors to BD, studies in unaffected first-degree relatives can identify neural mechanisms of genetic risk but also resilience, thus paving the way for preventive interventions. Dynamic causal modeling (DCM) and random-effects Bayesian model selection were used to define and assess connectomic phenotypes linked to facial affect processing and working memory in a demographically matched sample of first-degree relatives carefully selected for resilience (n=25), euthymic patients with BD (n=41) and unrelated healthy controls (n=46). During facial affect processing, patients and relatives showed similarly increased frontolimbic connectivity; resilient relatives, however, evidenced additional adaptive hyperconnectivity within the ventral visual stream. During working memory processing, patients displayed widespread hypoconnectivity within the corresponding network. In contrast, working memory network connectivity in resilient relatives was comparable to that of controls. Our results indicate that frontolimbic dysfunction during affect processing could represent a marker of genetic risk to BD, and diffuse hypoconnectivity within the working memory network a marker of disease expression. The association of hyperconnectivity within the affect-processing network with resilience to BD suggests adaptive plasticity that allows for compensatory changes and encourages further investigation of this phenotype in genetic and early intervention studies.
“Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder” by D Dima, R E Roberts and S Frangou in Translational Psychiatry. Published online January 5 2016 doi:10.1038/tp.2015.193