Bipolar Disorder May Rewire the Brain's Communication Network

Scans of 449 people with bipolar disorder and 510 controls across 16 sites found less efficient, more roundabout brain wiring in emotion and reward circuits, with the disruption tracking illness duration and severity.

Using diffusion MRI, which maps the brain's white-matter wiring, an international team examined structural connectivity in 449 people diagnosed with bipolar disorder and 510 healthy controls across 16 research sites worldwide, coordinated through the ENIGMA Bipolar Disorder Working Group. Rather than looking at single brain regions, they modeled the brain as a network and measured how efficiently different regions communicate with each other. People with bipolar disorder showed less densely connected networks, longer communication paths between regions, and greater reliance on a small number of 'hub' regions to relay signals -- changes concentrated in circuits tied to emotion regulation, reward processing, and memory, including connections between the amygdala, hippocampus, and frontal cortex. These network disruptions were more pronounced in people with longer illness duration, later age of first episode, and a history of psychosis, while a higher number of past manic episodes was linked to unexpectedly stronger connectivity in some emotion-related circuits. Common medications, including antidepressants, anticonvulsants, and antipsychotics, were associated with reduced connectivity in some circuits, though the effect of lithium was unclear. Because the study captured each person's brain at a single point in time rather than tracking them over years, the researchers can't say whether these network changes cause worsening symptoms, result from them, or simply reflect medication exposure -- only that they travel together.