Genes link bipolar, schizophrenia, which are thought to be unrelated

Elizabethtown, Kentucky. When Chastity Murry had her first psychotic break, she went into her bathroom and dropped an entire bottle of pills, hoping she would die. Her teenage daughter had to perform CPR to save her life.

At about the same time more than a decade ago, the man who became her husband, Dante Morey, also lost touch with reality and deemed it suicide.

Different illnesses led them down similar paths—bipolar disorder in her case and schizoaffective disorder in his case—conditions that many have long considered separate and unrelated.

But a growing body of research shows that bipolar disorder, schizophrenia, and schizoaffective disorder diagnoses share common genetic underpinnings as well as overlapping symptoms and signs.

“They can be considered part of a spectrum,” said Dr. Morgan Sheng, who co-directs the Center for Psychiatry Research at MIT’s Broad Institute and Harvard University.

Bipolar disorder is known to cause extreme mood swings. Schizophrenia is characterized by delusions, hallucinations, and disturbed thinking. Schizoaffective disorder includes symptoms of both.

The theory that they are on a continuum is gaining ground as more and more studies have found that differences in some of the same genes affect how susceptible people are to these conditions. One of the most recent examples is the AKAP11 gene, which scientists at Broad and elsewhere identified as a strong risk factor for bipolar disorder and schizophrenia in research published in the journal. natural genetics this year.

Experts say these insights will help doctors better understand what causes diseases, how they affect the body’s most elusive organ, and what can be done to help people. In the future, experts envision the research could help guide treatment and lead to better drugs. For now, they hope, this will reinforce the idea that such disorders are biologically rooted and not moral failures or mysterious, unknown circumstances.

“This is what the science is giving us – a clear indication that there are genetic markers and risk factors,” said Dr. Ken Duckworth, chief medical officer of the National Alliance on Mental Illness.

The Morris – who met through the alliance and married in 2020 – hope the research will provide answers to them and the many other mentally ill people they have come to know. With the help of doctors and each other, they keep their disorders under control and find a purpose to help others in similar distress.

Chastity Morey, 48, called them ideal partners. “It’s peanut butter. I’m jelly.”

“Yes,” Dante Morey, 50, added with a smile. “She is sweeter than me.”

Bypass the terms of the puzzle

She says mental illness runs in both of their families — and haunts her for at least five generations.

Knowing this “helped me understand why this happened to me,” Chastity Morey said. “This possibility has always existed.”

Genes play a large role in bipolar disorder, schizoaffective disorder, and schizophrenia, Sheng said. But experience and environment also play a big role, and these things interact in subtle ways. So it’s not as if everyone with risky genes will get the disease.

A high-risk gene for schizophrenia, for example, may increase the chance of developing the disease tenfold, Morgan said. But that only brings it to 10%, because the risk of developing the disease at the population level is 1%. Given these possibilities, parents who have the gene may not have any children with the disease.

“If you take a whole family that has this dangerous gene, a number of cases will arise,” Morgan said. “It’s a roll of the dice.”

Experts say other illnesses that some call a “persistent cascade of psychosis” are also more likely. Dr. Fernando Jos, a psychiatrist at Johns Hopkins University, said:

Studies show that the same is true for schizoaffective disorder.

There are no tests for these conditions — which together affect about 9 million American adults — so diagnosis is based on history and sometimes overlapping symptoms. For example, psychosis can occur in all three diseases.

This can make diagnosis difficult. Sally Littlefield of Oakland, California was diagnosed with bipolar disorder, then schizoaffective disorder, after spiraling into psychosis during a business meeting in 2018. For 10 months, she was convinced that a team of psychologists had taken control of her life and they were conducting experiments on it despite their will.

At one point during a frenzy, Littlefield roamed the streets of San Francisco, breaking into homes and cars, robbing stores and jumping from one rooftop to another. Eventually she was treated by the police and taken to the hospital. She realized she was sick when her delusions got so bad that she thought she was the president of the United States.

She said she is now doing well and would like to tell her story to help dispel stigma, discrimination and shame, which “prevent so many of us from recovering.”

very long journey

People with mental illness hope the stigma will fade as doctors learn more about how these disorders manifest and affect the brain.

a Study 2019 A growing number of experts now realize that schizophrenia, schizoaffective disorder and bipolar disorder not only share common genetic risk factors and symptoms but also appear similar on neuroimaging and may have common treatment regimens, he said. Lithium, a mood stabilizer, for example, is often used to treat bipolar disorder and schizophrenia. Recent research from the Broad Institute may provide clues to how the drug works, as AKAP11 interacts with what is believed to be a lithium target.

Other medicines also treat more than one disease. Morris takes many of the same medications.

One day, experts said, genetic insights may allow doctors to intervene early in the disease process. While few people are getting genetic testing now — except perhaps to see how they might interact with a particular drug — the scientists said this could change in the future. If people know their genetic risk and family history, Sheng said, they can seek help if something doesn’t seem right, before the disease causes major problems.

Some scholars, while recognizing the common genetic underpinnings of bipolar disorder, schizoaffective disorder, and schizophrenia, are skeptical about framing them as a psychotic continuum, especially if it changes the categories doctors use to diagnose people with each disorder. They say current standards are useful in determining treatment and care.

Scientists agree that more research is needed. Finding new disease risk genes, for example, is only the first step toward developing new drugs. An extensive “roadmap” says researchers must also discover how genes work, understand disease mechanisms and identify drug targets.

It may be “5 to 50 years” before the genetic findings translate into changes in clinical practice, said NAMI’s Duckworth. “It’s a very long journey.”

Meanwhile, many people with mental illness rely on peer support in addition to medication and psychotherapy. Murrys checks on each other daily.

“I can always tell when he’s having a bad day. He can always tell when I’m having a bad day,” said Chastity Morey, who’s also been diagnosed with borderline personality disorder and anxiety disorder. today? But I am not offended because I know he has my best interest in mind.”

Both also learned and grew from working as volunteers. Together, they facilitate support groups twice a week, check in with peers regularly over the phone, and have been trained to help people with suicidal tendencies.

“This is my way of life, and his way too,” said Chastity Morey. “We help them, but they also help us.”


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