Isak
© Adam McCune
A LAST SHOT: At first, Isak’s parents had no idea where their son’s violent tics and terrifying visions came from. Right around the time he snapped this photo, says his father, Adam McCune, Isak “stopped letting us take his picture. He would scream at the sight of seeing us raise our phones.”Adam McCune
A controversial disease revives the debate about the immune system and mental illness.

One day in March 2010, Isak McCune started clearing his throat with a forceful, violent sound. The New Hampshire toddler was 3, with a Beatles mop of blonde hair and a cuddly, loving personality. His parents had no idea where the guttural tic came from. They figured it was springtime allergies.

Soon after, Isak began to scream as if in pain and grunt at his parents and peers. When he wasn't throwing hours-long tantrums, he stared vacantly into space. By the time he was 5, he was plagued by insistent, terrifying thoughts of death. "He would smash his head into windows and glass whenever the word 'dead' came into his head. He was trying to drown out the thoughts," says his mother, Robin McCune, a baker in Goffstown, a small town outside Manchester, New Hampshire's largest city.

Isak's parents took him to pediatricians, therapy appointments, and psychiatrists. He was diagnosed with a host of disorders: sensory processing disorder, oppositional defiance disorder, and obsessive-compulsive disorder (OCD). At 5, he spent a year on Prozac, "and seemed to get worse on it," says Robin McCune.

The McCunes tried to make peace with the idea that their son might never come back. In kindergarten, he grunted and screamed, frightening his teachers and classmates. "He started hearing voices, thought he saw things, he couldn't go to the bathroom alone," Robin McCune says. "His fear was immense and paralyzing."

Other kids afflicted with PANDAS hear voices or experience "Alice in Wonderland" syndrome, wildly distorted perceptions.

As his behaviors worsened, both parents prepared themselves for the possibility that he'd have to be home-schooled or even institutionalized. Searching for some explanation, they came across a controversial diagnosis called pediatric autoimmune neuropsychiatric disorders associated with streptococci, or PANDAS. First proposed in 1998, PANDAS linked the sudden onset of psychiatric symptoms like Isak's to strep infections.

They didn't give it much thought. Periodic strep tests on Isak had always come back negative. And his symptoms seemed too dramatic to be the result of a simple, common childhood infection.

But as Isak's illness dragged into its fourth year, they reconsidered the possibility. The year before the epic meltdowns began, his older brother had four strep infections; perhaps it was more than coincidence. In September 2013, three and a half years after his first tics appeared, a pediatric infectious-disease specialist in Boston put Isak on azithromycin, a common antibiotic used to treat food poisoning, severe ear infections, and particularly persistent cases of strep throat.

The results were dramatic. Isak's crippling fear vanished within days. Then he stopped grunting. Less than a week after starting his son on the antibiotic, Adam McCune saw Isak smile for the first time in nearly four years. After a few weeks, the tantrums that had held the family hostage for years faded away.

Today, Adam McCune, a writer, likens the experience to welcoming his son back from captivity. "It's like he was a POW for four years, and returned out of the blue one day," he says. "To have my son back within a week was incredible."

PANDAS represents a striking branch of medical research that has been gaining acceptance in recent years, though not without controversy. In a field known as immunopsychiatry, researchers are exploring the possibility that inflammation, or an overactive immune system, is linked to mental disorders that include depression, schizophrenia, and Alzheimers' disease.

A host of recent genetic and epidemiological studies "have shown that when people are depressed or have psychotic episodes, inflammatory markers are found in their blood," says Golam Khandaker, a senior clinical research associate at the University of Cambridge, in England, who studies inflammation and the brain.

In the case of PANDAS, when the body reacts to strep infection, parts of the brain that help regulate motion and behavior wind up caught in the crossfire, mistaken for bacterial invaders by cells bent on destroying them. Eliminate the inflammation, some doctors say, and you signal the immune system to stand down, restoring normal brain function.

The emergence of immunopsychiatry is a story of rediscovery, reflecting the twists and turns of mental health treatment over the last century. In the 19th century, mental illness and infectious disease were closely linked. That connection came uncoupled in the 20th century and immunopsychiatry's argument that infection and inflammation can have a profound impact on the brain has struggled against psychiatric and neurological dogma. Yet emerging insights into mental illness unite the brain, body, and environment in ways that doctors and therapists are finally beginning to understand.

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