Mental and physical illnesses go hand in hand. A new genetic study helps explain why
Analysis of DNA from 2 million people shows same chunks of DNA often underly both
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.
“The surprising finding here is not that psychiatric disorders and medical disorders are linked, but rather, how much they are linked,” said senior author Andrew Grotzinger, assistant professor of psychology and neuroscience. “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.”
Journal
Nature Communications
Method of Research
Data/statistical analysis
Subject of Research
People
Article Title
Shared Genetic Liability across Systems of Psychiatric and Physical Illness
Study explores link between smoking, dementia
Direct signaling pathways between the brain and the lungs could be behind smokers’ higher dementia and neurodegeneration rates
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A new study from the lab of Asst. Prof. Joyce Chen at the University of Chicago Pritzker School of Molecular Engineering suggests a new reason why heavy midlife smoking can double the risk of dementia later in life.
view moreCredit: UChicago Pritzker School of Molecular Engineering / John Zich
The correlation between smoking and neurodegeneration is well-documented, with one study from 2011 finding heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, Alzheimer’s and vascular dementia more than two decades later.
Dementia is a less-studied impact of smoking for a simple, terrible reason. It occurs later in life and smokers tend to die younger.
Many of the theories around smoking and dementia relate to smoking’s impact on the vascular and respiratory systems – essentially choking the flow of oxygen to the brain over decades of tobacco use. But a new study from the University of Chicago published today in Science Advances suggests nicotine-triggered miscommunication between the lungs and the brain could be involved.
Their work found a previously unmapped route from the lungs to the mind through pulmonary neuroendocrine cells (PNECs). When exposed to nicotine, these cells release exosomes that disrupt the iron balance in neurons, triggering symptoms often found in dementia patients.
“This research establishes a clear ‘lung-brain' axis that helps explain why cigarette smoking is linked to cognitive decline and neurodegenerative risks,” said UChicago postdoctoral researcher Kui Zhang, co-first author of the new work. “By understanding how these exosomes perturb iron homeostasis, we open new doors for protecting neurons from smoke-induced damage.”
Whether this proves to be a causal link for dementia or not, the research itself is a powerful advance in scientists’ understanding of the lungs.
“It reveals that the lung is not just a passive target of smoke exposure, but an active signaling organ influencing brain pathology,” said corresponding author Asst. Prof. Joyce Chen of the UChicago Pritzker School of Molecular Engineering (UChicago PME) and the Ben May Department for Cancer Research.
From lung to brain
PNECs are unique lung cells that blend the functions of both nerve cells and endocrine cells. Speaking the languages of both synapse and hormone, they are important sensors for the airway, but difficult to study.
“The primary challenge was the extreme rarity of PNECs, which make up less than 1% of lung cells, making them nearly impossible to isolate and study in depth,” Zhang said.
To research these elusive but important cells, the team generated induced PNECs (iPNECs) by differentiating human pluripotent stem cells, in numbers large enough to research in the lab.
When exposed to nicotine, the iPNECs emitted great quantities of exosomes, tiny particles that contain biological material like proteins, lipid or nucleic acids. Most cell types produce exosomes, but the particular exosomes the iPNECs produced in response to nicotine were rich in a protein called serotransferrin, which the body uses to regulate the flow of iron through the bloodstream.
Applying this model to the human body could mean that with every puff of cigarette, cigar or vape, the lung’s natural PNECs blast out massive amounts of a material that impacts how the body handles iron.
“This nicotine will have an impact on the PNEC, and this PNEC will release a massive amount of exosomes, and that causes perturbation in terms of iron homeostasis,” said co-first author Abhimanyu Thakur, who was with UChicago PME and the Ben May Department during the research and is now at Harvard Medical School’s Department of Neurosurgery. “We are finding neurodegeneration-related markers, which are going up, and which can be linked with many cognitive and dementia-related diseases.”
Work ahead
This blast of serotransferrin would essentially be telling the body – wrongly – to change how it regulates iron. The vagus nerve, which snakes from the brain to organs throughout the body, regulating involuntary movement like heartbeats, breathing and digestion, would carry this message back to the brain.
“This iron dyshomeostasis drives oxidative stress, mitochondrial dysfunction, and increased α-synuclein expression – hallmarks of neurodegenerative disease,” Chen said.
An iron imbalance in neurons can also wrongly trigger ferroptosis, a form of programmed cell death, in cells that weren’t supposed to die. Previous research has associated ferroptosis with both Alzheimer’s and Parkinson’s, but much more study is needed before any causal link can be claimed.
The team is next looking to see if blocking the exosomes – the original source of the signal – could have therapeutic applications. While direct impact on humans is still years off, the research advances scientists’ understanding of how the brains and lungs communicate.
“Understanding these cross-organ communication pathways is critical for developing better prevention and intervention strategies for neurodegenerative diseases,” Chen said.
Citation: “Pulmonary Neuroendocrine Cell-derived Exosomes Regulate Iron Homeostasis and Oxidative Stress in Lung Neurons,” Thakur et al, Science Advances, April 8, 2026. DOI: 10.1126/sciadv.ady2696
Journal
Science Advances
Article Title
Pulmonary neuroendocrine cell–derived exosomes regulate iron homeostasis and oxidative stress in lung neurons
Article Publication Date
8-Apr-2026
Male gender, marriage, and social support linked to flourishing mental health for older Canadians
New study could inform public health strategies to enhance older adults’ mental health
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In the new study, Canadian adults aged 65 and older were more likely to have flourishing mental health if they were male, married, and reported having social support, important spiritual beliefs, and excellent health, among other characteristics.
view moreCredit: Age without Limits (https://www.agewithoutlimits.org/i), CC0 (https://creativecommons.org/publicdomain/zero/1.0/)
In a new study, Canadian adults aged 65 and older were more likely to have flourishing mental health if they were male, married, and reported having social support, important spiritual beliefs, and excellent health, among other characteristics. Daniyal Rahim of the University of Toronto, Canada, and colleagues present these findings in the open-access journal PLOS One on April 8, 2026.
Researchers are increasingly interested in characteristics associated with high levels of emotional, psychological, and social well-being—often referred to as “complete” mental health. Multiple studies have found that older adults tend to score higher than younger adults on measures of complete mental health.
However, few studies have explored which characteristics are associated with complete mental health among older adults. To help clarify, Rahim and colleagues analyzed survey data collected from 2,024 Canadians aged 65 and older. They used the data to uncover statistical associations between personal characteristics and participants’ complete mental health—measured by their reports of experiencing life satisfaction, happiness, and social and psychological well-being nearly every day over the previous month, as well as lack of suicidality, mental illness, and substance use disorder over the previous year.
The analysis revealed that participants with complete mental health tended to be male, married, have social support, have spiritual or religious beliefs that were important to them, and have excellent health. Complete mental health was also more prevalent among participants who lacked chronic pain, had no difficulties with daily household responsibilities, had no trouble sleeping, and had no history of depression, anxiety, or substance use disorder.
Notably, people with social support were at least twice as likely to have complete mental health than people without. The researchers note that social support is one of several modifiable risk factors they identified, which could serve as targets for strategies to enhance older adults’ mental health. For instance, they suggest, efforts could include increasing access to social support programming, spiritual practices, and resources for addressing chronic pain, anxiety, and other concerns.
The researchers note that future research is needed to further strengthen understanding of mental health among older adults and the best strategies to help more people to flourish in later life.
Author Esme Fuller-Thomson adds: “We often hear narratives that portray aging in bleak terms, but our findings paint a much more hopeful picture. Three-quarters of older adults are not only free of mental illness but are thriving emotionally, socially, and psychologically.”
“One striking finding was how strongly social support, pain-free living, and healthy sleep patterns were linked to flourishing in later life. These are areas where targeted interventions could make a meaningful difference for older adults.”
“One of the most uplifting findings was how much support from friends and family matters. Older adults with people they can count on were far more likely to feel happy and be free of any mental health problems.”
In your coverage, please use this URL to provide access to the freely available article in PLOS One: https://plos.io/4dJvGpP
Citation: Rahim D, Halls SK, Jiang Y, Fuller-Thomson E (2026) Flourishing older Canadians: What characteristics are associated with complete mental health? PLoS One 21(4): e0344898. https://doi.org/10.1371/journal.pone.0344898
Author countries: Canada
Funding: DR received funding from the Public Health Agency of Canada’s Federal Student Work Experience Program (FSWEP) to support this research activity. The funders had no role in study design, data collection or decision to publish.
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