Who would have guessed that a single dose of an antidepressant could alter the functional arrangement of the brain within a few short hours, considering that patients who take these drugs do not experience their effects until several weeks after beginning their use? Turns out that this is exactly what happens: changes in brain connectivity within three hours after one dose. The findings were published Thursday in the journal Current Biology.

“We were not expecting the SSRI to have such a prominent effect on such a short timescale or for the resulting signal to encompass the entire brain,” said study co-author Julia Sacher of the Max Planck Institute for Human Cognitive and Brain Sciences in a statement.

Even though selective serotonin reuptake inhibitors, more commonly known as SSRIs, are widely used to treat depression and have been extensively studied, the exact mechanism for how they work is still a mystery. Experts have generally believed that the drugs caused changes in brain connections but that these changes took much longer to happen.

Sacher and colleagues at the Max Planck Institute in Leipzig, Germany, conducted a magnetic resonance imaging-based investigation into the gray matter connections formed in the brains of subjects who took SSRIs compared with subjects who did not. The team was particularly interested in what was happening in the brains of the two subject groups while they were not thinking of anything in particular.

“We just tell them to let their minds wander and not think of anything particularly dramatic or upsetting,” said Sacher.

The researchers made observations based on a discovery made more than a decade ago which holds that low-frequency brain activity during inactivity like daydreaming is a good indicator of functional connectivity. They mapped the gray matter connections in 3D, considering both anatomical and connection and interdependence.

One observation confirmed what was already believed: more available serotonin in the gay matter meant decreased functional connectivity. However, some brain areas did not follow this pattern but became more interdependent. Another surprise was that this occurred within only three hours of a single SSRI dose.

“It was interesting to see two patterns that seemed to go in the opposite direction,” Sacher said. “What was really surprising was that the entire brain would light up after only three hours. We didn’t expect that.”