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Genes link bipolar, schizophrenia, once thought unrelated

Genes link bipolar, schizophrenia, once thought unrelated

ELIZABETHTOWN, Ky. (AP) – When Chastity Murry had her first psychotic break, she went into her bathroom and drank an entire bottle of pills, hoping to die. Her teenage daughter had to perform CPR to save her life.

Around the same time more than a decade ago, the man who would become her husband, Dante Murry, also lost touch with reality and contemplated suicide.

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

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

“They can be considered part of the spectrum,” said Dr. Morgan Sheng, co-director of the Psychiatric Research Center at the Broad Institute of MIT and Harvard.

Bipolar disorder is known for causing extreme mood swings. Schizophrenia is characterized by delusions, hallucinations, and disordered thinking. Schizoaffective disorder includes symptoms of both.

The theory that they exist on a continuum has gained traction as more studies have found that variations 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 the Broad and elsewhere highlighted as a strong risk factor for bipolar disorder and schizophrenia in research published in the journal Nature Genetics this year.

Experts say these insights will help doctors better understand what triggers diseases, how they affect the most notoriously confusing organ and what more can be done to help people. Going forward, experts predict the research could help guide treatment and lead to better drugs. For now, they hope it reinforces the idea that such disorders are biologically rooted, not moral failings or mysterious, unknowable conditions.

“That’s what science gives 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 Murrys – who met through an alliance and married in 2020 – hope the research will provide answers for them and the many others with mental illness they have met. With the help of doctors and each other, they keep their disorders under control and have found purpose in helping others in similar situations.

Chastity Murry (48) called them perfect partners; “He’s peanut butter; I am jelly.”

“Yes,” Dante Murry (50) added with a smile. “She’s cuter than me.”

TRANSFER OF MYSTERIOUS TERMS

Mental illness runs in both of their families – haunting hers for at least five generations, she says.

Learning about this “helped me understand why this was happening to me,” Chastity Murry said. “That possibility was always there.”

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

Morgan said a serious risk gene for schizophrenia, for example, can increase the chance of getting the disease 10-fold. But this only brings it to 10%, because the risk of developing the disease in the entire population is 1%. Given these odds, parents with the gene may not have children with the disease.

But “if you take the whole extended family that has that risk gene, there’s going to be a cascade of cases,” Morgan said. “It’s a roll of the dice.”

Experts say other illnesses that some call the “psychosis continuum” are more likely. “When you look at a family, if you have one person with schizophrenia, you’re more likely to have schizophrenia yourself, but you’re also more likely to have bipolar,” said Dr. Fernando Goes, psychiatrist from Johns Hopkins University.

The same is true for schizoaffective disorder, studies show.

There are no tests for these conditions — which together affect about 9 million adults in the U.S. — so diagnosis is based on medical 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 she slipped into psychosis during a work meeting in 2018. For 10 months, she was convinced that a team of psychologists had taken control of her life and were experimenting on her. against her will.

At one point during the manic episode, Littlefield roamed the streets of San Francisco, breaking into houses and cars, stealing and jumping from one car roof to another. She was eventually caught by the police and hospitalized. She realized she was sick when her delusions became so grandiose that she believed she was the President of the United States.

She said she is now fine and ready to share her story to help end the stigma, discrimination and shame that “holds so many of us from recovery.”

‘A VERY LONG JOURNEY’

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

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

Other drugs also treat more than one disease. The Murrys take several of the same medications.

One day, experts said, genetic insights could allow doctors to intervene earlier in the disease process. Although few people now undergo genetic testing—except perhaps to see how they might respond to a particular drug—scientists say that could change in the future. If people knew their genetic risk and family history, Sheng said, they could seek help if something was wrong, before the disease caused major problems.

Some scientists, while acknowledging the common genetic underpinnings of bipolar, schizoaffective disorder, and schizophrenia, are skeptical of framing them as a continuum of psychosis, especially if it changes the categories doctors use to diagnose people with each disorder. They say the current criteria are useful in making treatment and care decisions.

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

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

Meanwhile, many people living with mental illness rely on peer support in addition to medication and psychotherapy. The Murrys are checked on daily.

“I always know when he’s having a bad day. He can always tell when I’m having a bad day,” said Chastity Murry, who has also been diagnosed with borderline personality disorder and anxiety disorder. “If I act a little bit or something, he’ll ask me: did you take your medicine today? But I’m not offended because I know he has my best interests in mind.”

Both also studied and grew up working as volunteers. Together they run support groups twice a week, regularly check in with peers over the phone and are trained to help people who are suicidal.

“This is my path in life, and it’s his path,” Chastity Murry said. “We help them, but they also help us.”

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The Associated Press Department of Health and Science receives support from the Howard Hughes Medical Institute’s Division of Science Education. AP is solely responsible for all content.



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