NEW YORK – This month a conference at the Stavros Niarchos Foundation will present findings of a study that could be a breakthrough in treating psychiatric patients with severe disorders, targeting autoimmune causes.
The groundbreaking work that resulted in remarkable recoveries of two women lost in the dark of a catatonic state helped inspire the SNF Center for Precision Psychiatry and Mental Health at Columbia, funded with a $75 million grant.
The goal of the center is to develop new treatments based on specific genetic and autoimmune causes of psychiatric illness, Joseph Gogos, Co-Director of the SNF Center told The Washington Post.
A feature written by Richard Sima, a neuroscientist turned science journalist who writes the Brain Matters column for the newspaper, followed the treatments of April Burrell and Devine Cruz, after it was found autoimmune diseases likely worsened their cases.
Sander Markx, Director of Precision Psychiatry at Columbia University, first met Burrell while he was medical student in 2000 and said he always remembered a then young woman lost in her own darkness, unmoving.
“She was the first person I ever saw as a patient,” he told the newspaper of how she moved him – and what led him back to her. “She is, to this day, the sickest patient I’ve ever seen.”
After identifying that she had lupus and working on that helped her come back after a series of treatments, it led to the case of Cruz, who similarly was aided after an autoimmune disease was linked to her psychiatric state, both suffering from schizophrenia.
Markx said he has begun care and treatment on about 40 patients since the SNF Center opened, the piece noted, in hopes that it could lead to finding the cases of psychiatric conditions of others.
The SNF Center is working with the New York State Office of Mental Health, overseeing one of the largest public mental health systems in America, on whole genome sequencing and inpatient autoimmunity screening at long-term facilities.
If it seems like a movie, it’s because it resembles one: Awakenings, inspired by a book by the late neurologist and writer Oliver Sacks starring Robin Williams and Robert DeNiro and cases like those of Burrell and Cruz.
It was 18 years between meetings for Markx with Burrell who had been had been an outgoing, straight-A student majoring in accounting at the University of Maryland Eastern Shore before a traumatic event when she was 21.
It wasn’t identified to protect her privacy but the report said after it happened that she developed psychosis and became lost in a constant state of visual and auditory hallucinations and couldn’t communicate, bathe or care for herself.
WHO KNOWS WHAT LURKS?
She was diagnosed with a severe form of schizophrenia but Markx said when he came back that he and colleagues discovered she also had lupus, an underlying and treatable autoimmune condition that was attacking her brain.
After months of targeted treatments – and more than two decades trapped in her mind – she woke up, astonishing everyone and creating hope that others like her languishing in their own minds could be helped too.
Researchers working with the New York state mental health-care system have identified about 200 patients with autoimmune diseases, some institutionalized for years, who may be helped by the discovery, the report said.
Scientists around the world, including Germany and Britain, are conducting similar research, finding underlying autoimmune and inflammatory processes may be more common in patients with a variety of psychiatric syndromes than first believed.
While the current research probably will help only a small subset of patients, the impact of the work is already beginning to reshape the practice of psychiatry and the way many cases of mental illness are diagnosed and treated.
“These are the forgotten souls,” said Markx. “We’re not just improving the lives of these people, but we’re bringing them back from a place that I didn’t think they could come back from.”
It was Burrell who led him to the discovery, he said, never forgetting what he first saw, a young woman stationary by a nurse’s desk. “She would just stare and just stand there,” Markx said. “She wouldn’t shower, she wouldn’t go outside, she wouldn’t smile, she wouldn’t laugh. And the nursing staff had to physically maneuver her.”
By 2018 he had a lab of his own and encouraged one of his research fellows, Anthony Zoghbi, to work at the facility, the Pilgrim Psychiatric Center, startled when the trainee told him of seeing a woman standing at the desk.
“It was like déjà vu because he starts telling the story,” said Markx. “And I’m like, ‘Is her name April?’”
Markx said he was stunned to find she was the same despite a series of treatments that included antipsychotics, mood stabilizers and electroconvulsive therapy, none of which worked.
He got her family’s permission for a full medical workup and brought together a team of more than 70 experts from Columbia and around the world — neuropsychiatrists, neurologists, neuroimmunologists, rheumatologists, medical ethicists — to figure out what was going on.
The first conclusive evidence was in her bloodwork: It showed that her immune system was producing copious amounts and types of antibodies that were attacking her body.
Brain scans showed evidence that these antibodies were damaging her brain’s temporal lobes, areas that are implicated in schizophrenia and psychosis.
The team hypothesized that these antibodies may have altered the receptors that bind glutamate, an important neurotransmitter, disrupting how neurons signals to one another.
WHAT ONLY THEY CAN SEE
While Burrell had all the clinical signs of schizophrenia, the team believed that the underlying cause was lupus, a complex autoimmune disorder in which the immune system turns on its own body,
The autoimmune disease, it seemed, was a specific biological cause — and potential treatment target – for the neuropsychiatric problems she faced and Markx said he wondered how many other patients there were like her.
It took months but she made a recovery and was able to leave the psychiatric hospital for a rehabilitation center.
After the unexpected recovery the medical team put out an alert to the hospital system to identify any patients with antibody markers for autoimmune disease which led to Cruz, who was only 9 when she began hearing voices.
For more than a decade, the young woman moved in and out of hospitals for treatment. Her symptoms included visual and auditory hallucinations, as well as delusions that prevented her from living a normal life, said the report.
He was eventually diagnosed with schizoaffective disorder, which can result in symptoms of both schizophrenia and bipolar disorder. She also was diagnosed with intellectual disability. She also was found to have lupus too.
A medical team prescribed monthly immunosuppressive infusions of corticosteroids and chemotherapy drugs, similar to that of Burrell and in a short time there were dramatic signs of improvement.
The voices and visions have stopped. And she no longer meets the diagnostic criteria for either schizoaffective disorder or intellectual disability, Markx said, and she now realizes her delusions weren’t real.
She lives with her mother and has a more active and engaged life. She helps her mother cook, goes to the grocery store and navigates public transportation to keep her appointments and babysits her siblings children.
She is grateful for her treatment and the team that made it possible. “Without their help, I wouldn’t be here,” Devine said. “I feel more excited,” she said. “Like a new chapter is beginning.”
The findings also are leading to more targeted immunotherapy instead of the so-called “sledgehammer approaches” that suppress the immune system on a broad level, said George Yancopoulos, the co-founder and president of the pharmaceutical company Regeneron. “I think we’re at the dawn of a new era. This is just the beginning,” said Yancopoulos.
Markx will be at the SNF conference to present the findings and so will Cruz to share her story, but not Burrell, who is turning 50 and is still in the rehabilitation center, regressing because she didn’t get adequate maintenance care, he said.
“The message I want to give people is that there is time to heal,” Devine said. “There’s time to heal yourself from many obstacles you’ve been facing in life.”