"What surprised me most was how specifically the measure tracked the depression-related behavior," said Airan. "We usually think of psychiatric disorders as fuzzy and intractable, and this study showed me that, with the right tools, we could really put psychiatry on a quantitative framework."
Leslie Meltzer, neurosciences graduate student and co-first author, searched for the cellular basis of these changes in circuitry. An obvious place to start, she said, was to look at the formation of new neurons in the hippocampus, a process that neuroscientists have suggested is at the root of how antidepressants work. What they found was that the growth of new neurons could account for the behavioral improvements seen from treatment as well as the circuitry changes. The converse was not true: Fewer new neurons in that region did not equal depression.
In other words, in their model system, the two states appear to funnel through a common pathway--despite very different cellular mechanisms.
"The holy grail of psychiatry is to try to find final common pathways that can make sense of how genes and life experiences end up with the same result," said Deisseroth. "And the same goes for medications. There are many treatments that act in fundamentally different ways--how do we make sense of all that complexity?"
Deisseroth predicted that, as noninvasive imaging of human brains gets better in the next few years, researchers will be able to measure these same quantitative measures in people as well. "That will be a wonderful thing when that happens," he said.
Others who contributed to this work are: Madhuri Roy, basic life
sciences research associate; Yuqing Gong, a graduate student at the
time in statistics and electrical engineering, and Han Chen, a
graduate student in electrical engineering. This work was funded by
the National Institutes of Health (including Deisseroth's Pioneer