Genes link bipolar, schizophrenia, once thought to be unrelated

ELIZABETHTOWN, Ky. (AP) – When Chastity Murry had her first psychotic break, she went to the bathroom and swallowed a whole 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 thought about suicide.

Different illnesses have taken them on similar paths – bipolar disorder in his case and schizoaffective disorder in his – conditions long considered by many to be distinct and unrelated.

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

“They can be seen as part of a spectrum,” said Dr. Morgan Sheng, who co-directs a psychiatric research center at the Broad Institute of MIT and Harvard.

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

The theory that they exist on a continuum has gained ground as more and more studies have found that variations in some of the same genes affect people’s sensitivity to these conditions. One of the latest examples is the AKAP11 gene, which scientists from Broad and elsewhere have identified as a strong risk factor for bipolar disorder and schizophrenia in research published this year in the journal Nature Genetics.

Experts say these insights will help doctors better understand what drives diseases, how they affect the body’s most notoriously baffling organ, and what more can be done to help people. Along the way, experts predict that research could help guide treatment and lead to better medications. For now, they hope it reinforces the idea that such ailments are biologically rooted and not moral deficiencies or mysterious and unknowable conditions.

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

The Murries, who met through the alliance and got married in 2020, hope the research will provide answers to them and to the many others with mental illness they have gotten to know. With the help of doctors and with each other, they keep their ailments in check and have found a purpose in helping others in similar conditions.

Chastity Murry, 48, called them perfect partners; “He is peanut butter; I am the jelly “.

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


Mental illness is present in both of their families, haunting her for at least five generations, she says.

Knowing this “helped me understand why this is happening to me,” said Chastity Murry. “That possibility has always been there.”

Sheng said genetics play an important role in bipolar disorder, schizoaffective disorder, and schizophrenia. But experience and the environment also play an important role and these things interact in subtle ways. So it’s not like everyone with risk genes is bound to get sick.

Morgan said a severe risk gene for schizophrenia, for example, can increase the chance of getting the disease 10 times. But this only brings it to 10%, since 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 an entire extended family that has that risk gene, there will be a number of cases that will arise,” Morgan said. “It’s a roll of the dice.”

Experts say other illnesses along what some call the “psychotic continuum” are also more likely. “When you look at a family, if you have a schizophrenic person, you are more likely to have schizophrenia, but you are also more likely to have bipolar,” said Dr. Fernando Goes, a psychiatrist at Johns Hopkins University.

The same goes for schizoaffective disorder, according to studies.

There are no tests for these conditions – which together affect an estimated 9 million U.S. adults – so the 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, later schizoaffective disorder, after plunging into a spiral of psychosis during a business meeting in 2018. For 10 months, she was convinced that a team of psychologists had hired control of her life and experimenting on her against her will.

At one point, during a manic episode, Littlefield wandered the streets of San Francisco, breaking into homes and cars, stealing from shops, and jumping from roof to roof. She was eventually assaulted by the police and hospitalized. She realized she was sick when her disappointments became so great that she believed she was the president of the United States.

She said she is now doing well and willing to tell her story to help dispel the stigma, discrimination and shame, which “prevents many of us from recovering.”


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

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

Other drugs also treat more than one of the diseases. The Murries take many of the same drugs.

One day, experts said genetic insights could allow doctors to intervene earlier in the disease process. While few people now undergo genetic testing, except perhaps to see how they might react to a particular drug, scientists have said that may change in the future. If people knew their genetic risk and family history, Sheng said, they could ask for help if something doesn’t seem right, before a disease causes serious problems.

Some scientists, while acknowledging the common genetic underpinnings of bipolar, schizoaffective, and schizophrenic disorder, are skeptical of framing them as a psychotic continuum, particularly if this leads to changing the categories doctors use to diagnose people with each disorder. . They say the current criteria are helpful in deciding on treatment and cure.

Scientists agree that more research is needed. Finding new disease risk genes, for example, is only the first step towards developing new drugs. An extensive road map states that researchers also need to understand how genes work, understand disease mechanisms, and identify targets for drugs.

NAMI’s Duckworth said it could take “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 Murries check each other out every day.

“I can always tell when he’s having a bad day. He always knows when I’m having a bad day, “said Chastity Murry, who has also been diagnosed with borderline personality disorder and anxiety disorder. he will ask: Did you take your meds today? But I’m not offended because I know he has my best interest in mind. “

They both also learned and grew up working as volunteers. Together, they facilitate twice-weekly support groups, regularly check peers over the phone, and have been trained to help people who are suicidal.

“This is my path in life, and also his path,” said Chastity Murry. “We are helping them, but they are also helping us.”


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

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