Genetic overlap links psychiatric disorders with many physical ailments

For centuries, mental illness and physical disease have been viewed as two distinct categories, each with its own field of study, its own doctors, and its own menu of treatments.

New University of Colorado Boulder research calls that age-old dichotomy into question, showing that the same chunks of DNA that underly psychiatric disorders like depression, PTSD and ADHD are associated with risk of a host of physical ailments, too.

The study of nearly 2 million people, published in the journal Nature Communications, sheds light on just how often, and why, psychiatric and physical diseases go hand in hand. It could ultimately pave the way for new therapies that address both, the authors said.

Andrew Grotzinger, senior author, assistant professor of psychology and neuroscienceThe surprising finding here is not that psychiatric disorders and medical disorders are linked, but rather, how much they are linked. At the genetic level, we found that there is so much overlap they are really not two different classes of diseases at all."

Diseases come in pairs

Grotzinger's previous research has shown that people with one psychiatric disorder often have many (41% meet the criteria of four or more), likely due to shared genetic factors. Physical disorders also come in groups, with 38% of the global population having two or more chronic conditions.

Only recently have scientists begun to explore how often physical and psychiatric disorders coincide. One recent study, looking at medical records of Danish citizens, found that having a mental health disorder boosted risk of a physical disease by 37%, with some psychiatric disorders increasing risk of some physical disorders by nearly 400%. People with depression, studies show, are 1.5 times as likely as those without depression to develop heart disease.

"In the clinic, you rarely see someone with just one condition walk into a room," said first author Jeremy Lawrence, a PhD candidate in clinical psychology. "If we can better understand the cross-talk between these conditions, we can do a better job helping the whole patient."

To determine just how common these physical-mental combinations are, Grotzinger and Lawrence analyzed genetic material and health information from 1.9 million people.

They looked at which chunks of DNA are associated with 73 physical outcomes across eight medical domains (neurological, respiratory, circulatory, digestive, endocrine/metabolic, genitourinary, musculoskeletal, and cancer). Then they did the same with 13 psychiatric disorders across five categories (compulsive, psychotic/thought, neurodevelopmental, internalizing, and substance abuse).

When comparing physical and mental disorders, the genetic risk factors overlapped 42% of the time.

"We found that, at the genetic level, the shared risk between psychiatric and non-psychiatric medical disease is pervasive and substantial," said Lawrence.

Neurodevelopmental disorders, like ADHD, were most likely to be associated with physical illnesses. In the case of ADHD, it had more in common, genetically, with physical diseases than with other psychiatric diseases.

Major depression, PTSD and substance use disorders also had high levels of shared risk with physical illnesses. In contrast, compulsive disorders like obsessive compulsive disorder and Tourette syndrome, were seldom associated with physical illnesses and seemed to have a protective effect when it came to digestive disorders.

Some specific diseases tended to go together.

For instance, schizophrenia tended to pair with gastrointestinal problems; Bipolar disorder tended to pair with genitourinary disorders and sleep problems. Depression and anxiety tended to pair with cardiovascular disease.

The chicken or the egg?

Lawrence noted that having a mental illness, like depression, could lead to behaviors - like eating poorly or leading a sedentary lifestyle - that precipitate poor physical health. In other cases, like a cancer diagnosis, physical illness could boost risk of mental illnesses like depression. In some cases, a common chunk of DNA may independently boost risk of both a physical illness and a mental illness.

Lawrence imagines a day when therapies could be developed that hit both physical and mental health targets at once.

He pointed to GLP-1 agonists - originally developed for diabetes, then prescribed for weight loss, and now showing promise for use in substance abuse disorders - as an example of how drugs meant for physical disease are making their way into the mental health realm.

Genetics could also be used to predict which groupings of diseases across the mental and physical spectrums a person is susceptible to so they can intervene early.

For now, the research shows that addressing mental illness can go a long way in improving overall health, said Grotzinger. It could also help break down the silos between psychology and general medicine.

"You can ask someone to spit in a tube or put a blood pressure cuff on to diagnose physical illness, but in many ways, we don't have that for psychiatric disorders, so some have viewed them as more esoteric and less tangible," said Grotzinger. "Psychiatric disorders are just as real as any medical disease. Our findings help make that argument."

Source:

University of Colorado at Boulder

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