Stony Brook University researchers edge closer to new OCD treatment

A research team led by Stony Brook University scientists has identified a little-observed neural pathway as a possible key to obsessive-compulsive behavior, a discovery that could lead to new treatments for a disorder that affects millions of Americans.

The researchers discovered a direct path through which the amygdala, a region of the brain that processes fear and anxiety, regulates activity in a portion of the dorsal striatum, which shapes habit formation.

By repeatedly activating the pathway in the brains of laboratory mice exposed to stimuli, the researchers induced OCD-like grooming, and by inhibiting the amygdala’s activity in mice engineered to exhibit that behavior, they were able to moderate the grooming. The study was published in the science journal Neuron.

One theory of OCD is that it emerges when the brain’s habitual system gets "captured," and instead of "goal-directed activities — for example, you wash your hands and you’re done," a person repeats an action over and over, said Dr. Benjamin D. Greenberg, professor of psychiatry and human behavior at Brown University’s Alpert Medical School. Greenberg, a member of the International OCD Foundation's advisory board, was not involved in the study.

While scientists have implicated other brain circuits in OCD, the researchers "seem to have found a new connection within a relevant brain network," Greenberg said. "The question becomes, then, what does this pathway look like in humans and does it lead to a new target for brain circuit-focused treatments for OCD" such as the pacemakerlike implants that deliver electrical pulses to modify brain activity, a treatment called deep brain stimulation.

Researchers employed an array of "circuit-tracing" methods to observe brains in action, using mice because their genes and brain anatomy are similar to humans’.

Joshua Plotkin, an associate professor in the neurobiology and behavior department in Stony Brook’s Renaissance School of Medicine, led the research, working with colleagues including Zachary Hobel, a postdoctoral fellow in the department.

They dripped water on the snouts of the mice over 10-minute intervals, eliciting a simple grooming response — the mice used their paws to wipe the water away.

They also implanted a fiber-optic device in the brains of mice in the experimental group, firing it to activate the amygdala-dorsal striatum pathway. When activated on its own without the water stimulus, the pathway produced no behavioral changes, but when the pathway was activated with the stimulus, the mice doubled the time they spent grooming. The behavior persisted even after researchers stopped firing the device and stopped the water — a long-lived, OCD-like habit.

When researchers examined the brains of the mice engineered to exhibit OCD-like behaviors, they found the pathway was pathologically strengthened. But the researchers found they could mitigate those behaviors through chemogenetics — a technique that uses drugs to control cells — that inhibited the amygdala’s activity.

"This is not the treatment that we would propose for patients," Plotkin said. "What we’ve worked out is what’s happening in the mouse brain, and while there are a lot of parallels, things need to be confirmed in the human brain."

Simply shutting off all of the amygdala’s anxiety regulation, as the researchers did for the mice, would be unwise to attempt in humans, Plotkin said.

"It’s important to check that the oven is off, that the door is locked," he added. "We have to be careful about what we choose to correct."

But the researchers’ work does suggest that treatments far more targeted than those currently prescribed could be viable, Plotkin said. "It will be years, but I don’t think it’s a distant horizon — I think it’s the near future," he said.

That could be especially important for OCD treatment because drugs commonly prescribed for the disorder, like SSRIs, can result in side effects, and a third or more of patients don’t respond to them, said Dr. Elias Aboujaoude, a clinical professor in Stanford University's psychiatry department, who was not associated with the study.

Dr. Helen Blair Simpson, professor of psychiatry at the Columbia University Vagelos College of Physicians and Surgeons, also not associated with the study, called it "a tour de force of the type of basic science that can be done today."

But discovery is, at most, a promising start to a long journey, she said; more research is needed to identify the human brain’s version of the pathway and translate lab findings into treatments.

By Nicholas Spangler

nicholas.spangler@newsday.comspanglernewsday

Nicholas Spangler is a general assignment reporter and has worked at Newsday since 2010.