Molecular Medicine Israel

Stronger Neural Connections May Trump Genetic Risk for Bipolar Disorder

Healthy siblings of people with the condition harbor more cohesive connections within certain brain networks.

EDITOR’S CHOICE IN NEUROSCIENCE
The paper
G.E. Doucet et al., “The role of intrinsic brain functional connectivity in vulnerability and resilience to bipolar disorder,” Am J Psychiat, doi:10.1176/appi.ajp.2017.17010095, 2017.

Ties that don’t bind
Bipolar disorder often runs in families, but genetics alone don’t determine whether one develops the disease, says Sophia Frangou of the Icahn School of Medicine at Mount Sinai. She and her colleagues wondered why siblings of affected people, despite having a slightly higher chance of developing mental illness, typically don’t.

In sync
Using fMRI, Frangou’s group previously found that, compared with the brains of bipolar patients, certain regions within healthy siblings’ brains responded more synchronously during memory and emotional processing tasks. To find out whether this reflects differences in brain organization, postdoc Gaelle Doucet imaged 78 people with bipolar disorder, 64 of their unaffected siblings, and 41 healthy, unrelated controls, all while they were doing nothing.

Compensatory connections
The sensorimotor network, which is important for integrating sensation and movement, was poorly connected in both bipolar patients and their healthy siblings compared with the control group. But, Frangou says, healthy siblings demonstrated stronger connections even than controls within the default mode network, “the backbone of the brain,” which contributes to recall and self-reflection—activities unrelated to specific tasks. It’s possible that the default mode network is “stepping up . . . and somehow regulating the sensorimotor network,” says Ellen Leibenluft of the National Institute of Mental Health.

Little to do with luck
Frangou emphasizes that avoiding disease is a matter of adaptive neural mechanisms. “We have to stop thinking about why people become unwell and question why people who have all the risks to become unwell stay well,” she says.

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