A brain changer for OCD – Sarasota Herald

By Amy Ellis Nutt

The computer screen and joystick are similar to those used with many virtual-reality games. It’s just that at the New York State Psychiatric Institute, the players compete while lying inside a highly sensitive MRI scanner.

In one challenge, the youths maneuver through a maze of corridors, searching for bright-green dollar signs. Another tests their ability to recognize an error on the screen. All the while, the scanner is photographing “slices” of their brains. The ultimate reward is far more than a game: In the first clinical trial of its kind, those multi-band images are mapping the unknown territory of obsessive-compulsive disorder.

Dr. Rachel Marsh, left, and Dr. Moira Rynn, right, look at participants' brain scans at the New York State Psychiatric Institute at Columbia University Medical Center.  Photo by Ryan C. Jones for The Washington Post.

Dr. Rachel Marsh, left, and Dr. Moira Rynn, right, look at participants’ brain scans at the New York State Psychiatric Institute at Columbia University Medical Center. Photo by Ryan C. Jones for The Washington Post.

The goal of psychologist Rachel Marsh is to uncover what goes wrong in the brain circuits of people with OCD, among the most intransigent of mental conditions. But the institute, part of Columbia University Medical Center, is probing on multiple fronts. Several investigators are tracking an intriguing but often overlooked neurochemical in patients. And still others are studying an antibiotic commonly used to treat acne, which they hope could be one of the missing pieces of the agonizing OCD puzzle.

“This is an illness that really gets people off track in their lives,” said Helen Blair Simpson, director of the Center for Obsessive-Compulsive and Related Disorders at Columbia. “And it tortures them.”

Approximately 1 in 40 American adults will be affected by obsessive-compulsive disorder at some point in their life, twice the rate of schizophrenia, according to the National Institute of Mental Health. The average age of onset for OCD is 19, earlier than most other mental illnesses. And more than 50 percent of people with an OCD diagnosis have severe symptoms.

All of these individuals battle persistent, intrusive thoughts, such as a fear of germs or a need for symmetry in their environment. They respond to these obsessive thoughts with ritualistic, repetitive behaviors: compulsions, such as counting their footsteps, excessively bathing, or endlessly checking that a door is locked.

“The difference between anxiety and other disorders, like schizophrenia, is there’s nothing normal about hearing voices. But anxiety is a safe emotion to have. It keeps you out of trouble,” said Moira Rynn, director of child and adolescent psychiatry at Columbia University.

Until, of course, it goes awry.

One main theory is that when the balance of activity is disturbed within the frontal lobe and mid-brain, cognitive and motor functions are affected.

The result: repetitive behaviors, or compulsions.

“A compulsion is like an itch,” said Jordan, a New Jersey high school student who asked to be identified only by his first name.

“It gets worse and worse if you don’t itch it. It drives you crazy.” Jordan’s “brand” of OCD falls into the “just right” category.

“I need to have everything feel just right,” he said. “When it’s not, it’s the most excruciating thing imaginable. It’s a feeling that just takes over you. You can never be happy again. You can’t go on. Everything is on the line.”

Jordan, 17, has felt this way, he says, “as long as I can remember.” The worries can come when he least expects them, and the rituals change all the time.

“People use OCD as a catchphrase: ‘That’s so OCD,’ ” said Jordan’s mother, Meg. “But it’s very different from that. I know how much my son suffers.”

The brain’s little hiccups

No one is sure why the disorder develops, although there are clearly genetic components with some people. When Jordan was 4, he would have a meltdown if his sleeves didn’t reach all the way to his wrist. When he was 7, he had to constantly rearrange the items on his desk at school.

At 12, he found it impossible to stop asking his teachers if he was doing the right thing.

“The brain, as it is developing, has little hiccups,” Rynn explained. “Everybody has their own trajectory. Most kids, the hiccups smooth out and pass, but for a small, significant subset of others, they do not.”

There are two traditional treatments for OCD: cognitive behavioral therapy and medication, with drugs chiefly targeting the neurotransmitter serotonin.

In combination, these treatments alleviate symptoms in up to 40 percent of adults. To have all symptoms disappear is rare.

But recently, scientists turned their attention to the amino acid glutamate. Some think this other neurotransmitter could be one of the chief culprits in OCD.

An accidental discovery in 2007 proved to be the breakthrough. Researchers at Duke University Medical Center had been examining how certain proteins provide a kind of infrastructure for the brain’s neurons. When they eliminated the Sapap3 protein from the OCD loop, mice turned anxious and exhibited obsessive-compulsive grooming behavior. They cleaned themselves so often and so vigorously that they developed bloody sores.

“People talk about serotonin this and serotonin that,” psychiatrist Suck Won Kim, an OCD expert at the University of Minnesota, wrote about the Duke study. “But the brain is a circuit and it’s a serious mistake to think that one neurotransmitter works alone. . . . This new finding will change the story of OCD.”

Repurposing drugs

It did. Others began to look for glutamate-modulating medications already approved by the Food and Drug Administration. At the New York State Psychiatric Institute, the researchers turned to a broad spectrum antibiotic called minocycline, which is used mainly for acne and infections as disparate as cholera and gonorrhea.

Animal investigations and other brain studies suggested minocycline might work for OCD by rebalancing glutamate levels critical to the obsession-compulsion pattern. Another significant factor: The drug was approved for use in children and adolescents.

Starting in 2012, children, adolescents and young adults, ages 8 to 20, were assigned either minocycline or a placebo to test whether the antibiotic changed glutamate levels in the mid-brain region. Afterward, each of the 50 participants was told what he or she had received and, if it was the minocycline, was given the opportunity of continuing on the medication.

Because the results are still being evaluated, the researchers don’t yet know exactly how many did.

A sense of dread

The suffering inherent with OCD was what initially piqued Simpson’s interest years ago.

Only later did she realize how much anxiety issues had affected people with whom she was close. Simpson knows the mysteries of the disorder remain daunting; solving them has become her own mission.

In the meantime, she and her colleagues are buoyed by victories such as Cory Muraglio.

The 22-year-old college student, who lives on Long Island, took part in a minocycline pilot trial. Before that, he was barely able to attend high school, scared of being contaminated by germs or poisoned by drinking water, and fearful that something dire would happen to his family.

His obsessions gave rise to ritualized compulsions.

Sometimes it was repeating a series of words at certain parts of the day, or washing his hands a specific number of times. But always the behavior arose out of an overwhelming sense of dread.

“When the rituals would start, I would try to resist,” he recounted recently. “But it’s like drowning. It was mental, physical, completely overwhelming, and if I was at school I couldn’t pay attention because of the thoughts that were in my head and the amount of energy and time they took up.”

Eventually, even school was too much.

“He wasn’t bathing; he couldn’t change his clothes. It was horrible,” said his father, Steve.

Once a week for three months, Steve drove Cory to the New York Psychiatric Institute’s OCD clinic in Manhattan, where his son received regular doses of minocycline.

Slowly, almost imperceptibly, the anxiety slipped away.

What happened next occurred just as gradually, but by the end of the 12-week study, Cory’s life was dramatically different.

“I can’t remember the moment I realized it,” he said. “I was pretty much symptom-less.”