Genes link bipolar, schizophrenia, once thought to be unrelated
When Chastity Murry had her first psychotic break, she went to her bathroom and swallowed 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 ten years ago, the man who would become her husband, Dante Murry, also lost touch with reality and contemplated suicide.
Different illnesses have led them down similar paths – bipolar disorder in her case and schizoaffective disorder in his – conditions long considered by many to be separate 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 considered 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 thought disorders. Schizoaffective disorder includes symptoms of both.
The theory that they exist on a continuum has gained traction as more studies have shown that variations in some of the same genes influence people’s susceptibility to these conditions. One of the latest examples is the AKAP11 gene, which scientists at Broad and elsewhere have identified as an important risk factor for bipolar disorder and schizophrenia in research published in the journal Nature Genetics this year.
Experts say this information will help doctors better understand what drives diseases, how they affect the body’s most notoriously confusing organ, and what more can be done to help people. Later, experts predict that the research could help guide treatment and lead to better drugs. For now, they hope this reinforces the idea that these disorders are biological in origin and not moral failings or mysterious, unknowable conditions.
« That’s what the 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 the wedding ring and married in 2020 – hope the research will provide answers for them and so many other people with mental illness they have come to know. With the help of doctors and each other, they control their disorders and have found purpose in helping others in similar situations.
Chastity Murry, 48, called them perfect partners; “He’s the peanut butter; I am jelly.
« Yes, » added Dante Murry, 50, with a smile. « She’s sweeter than me. »
Convey confusing conditions
Mental illness runs in both of their families — haunting hers for at least five generations, she says.
Knowing this « helped me understand why this is happening to me, » Chastity Murry said. « That possibility has always been there. »
Sheng said genetics plays an important role in bipolar disorder, schizoaffective disorder and schizophrenia. But experience and environment also play an important role, and these elements interact in subtle ways. So it’s not like everyone with risk genes is destined to get sick.
Morgan said a severe risk gene for schizophrenia, for example, can increase the risk of contracting the disease by a factor of 10. But that only brings it to 10%, since the population-wide risk of developing the disease is 1%. Given these probabilities, parents carrying the gene might not have children with the disease.
But « if you take an entire extended family that has this risk gene, there will be a number of cases that show up, » Morgan said. « It’s a roll of the dice. »
Experts say other illnesses along what some call the “psychosis continuum” are also more likely. « When you look at a family, if you have someone with schizophrenia, you’re more likely to be schizophrenic yourself, but you’re also more likely to be bipolar, » said Dr Fernando Goes, a psychiatrist at the ‘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 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 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 a manic episode, Littlefield roamed the streets of San Francisco, breaking into homes and cars, shoplifting, and jumping from car roof to car roof. She was eventually apprehended by the police and hospitalized. She realized she was sick when her delusions got so big she thought she was President of the United States.
She said she was fine now and was ready to tell her story to help dispel the stigma, discrimination and shame that « holds many of us back from recovery ».
A « very long journey »
People with mental illness hope the stigma will fade as doctors learn more about how these disorders arise and affect the brain.
A 2019 study found that a growing number of experts now recognize that schizophrenia, schizoaffective disorder, and bipolar disorder not only share common risk factors and genetic symptoms, but also resemble each other in neuroimaging and may have common treatment regimens. The mood stabilizer lithium, for example, is often used to treat bipolar and schizoaffective disorders. Recent Broad Institute research may provide clues as to how the drug works, since AKAP11 interacts with what is thought to be the target of lithium.
Other drugs also treat more than one disease. The Murrys take many of the same medications.
Experts once said that genetic knowledge could allow doctors to intervene earlier in the disease process. While few people currently undergo genetic testing – except perhaps to see how they might react to a particular drug – scientists said that may change in the future. If people knew their genetic risk and family history, Sheng said, they could seek help if something didn’t seem right, before an illness caused major problems.
Some scientists, while acknowledging the common genetic underpinnings of bipolar, schizoaffective disorder, and schizophrenia, are skeptical of framing them as on a continuum of psychosis, particularly if it leads to changing the categories doctors use to diagnose people with each disorder. They say the current criteria are helpful in deciding treatment and care.
Scientists agree that more research is needed. The discovery of new disease risk genes, for example, is only the first step towards the development of new drugs. A broad “roadmap” says researchers also need to understand how genes work, understand disease mechanisms, and identify drug targets.
NAMI’s Duckworth said it could be « 5 to 50 years » before genetic discoveries 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 check 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 Murry, who has also been diagnosed with borderline personality disorder and anxiety disorder. “If I act a little or something like that, he will ask me: did you take your medicine today? But I’m not offended because I know he has my best interest in mind.
Both also learned and grew by working as volunteers. Together, they lead support groups twice a week, communicate regularly with their peers by phone and have been trained to help suicidal people.
« It’s my path in life, and her path too, » Chastity Murry said. « We help them, but they also help us. »