When Physical Illness Is Mistaken for Mental Illness

For thirteen years, a man was treated for schizophrenia. Obsessive-compulsive disorder too. They gave him antipsychotics and years of therapy, and he kept getting worse. More delusional. More withdrawn. Turns out, he didn’t have schizophrenia, and doctors could have figured that out with a cheap blood test and a penlight eye exam.

He had a disease called Wilson’s, a genetic glitch that causes copper to build up in the body until it poisons the liver and the brain.¹ There’s an eye exam where you shine a light and look for a faint coppery ring around the cornea, and a blood test for the protein that impacts copper levels.² Both are cheap. Both are old. Neither is exotic. Once someone finally ran them, the thirteen-year mystery resolved in an afternoon.³

As if that weren’t bad enough, they later tested his sixteen-year-old brother (a kid who’d been written off as buckling under school stress). He had Wilson’s too.

Why weren’t they tested earlier?

When physical problems present as mental ones

This is a conundrum I’ve been drawn to for around four years now. Why do we treat mental health patients one way and “medical” or physical-health patients another way?

Depressed? See a psychologist. Migraines? See a doctor. Problem is, the body only has a limited vocabulary when it comes to telling us something is medically wrong. It can’t write us a detailed email, but it can call attention to problems through symptoms. It can make things sore or painful. It can power down parts of the body, discolor them or cause them to malfunction. It can also make us sad, tired, depressed, anxious or grumpy.

Mental health and physical health have historically been treated as separate universes. You can get caught, wrongfully, in the wrong one based on where you happened to seek help first. If you’re exhausted and have brain fog, you may wander into a doctor’s office and get a battery of blood tests. Alternatively, you could have just as easily wandered into a psychiatrist’s office and received years of talk therapy combined with antidepressants.

The Wilson’s example is a real one, but Wilson’s is rare; maybe thirty people in a million.⁴ I’m not arguing we should screen every anxious teenager for copper. I’m using it as an example of a wider pattern where, again, physical health issues often present (to caregivers and patients themselves) as mental health issues. Thyroid trouble can look like depression. Autoimmune disease can look like psychosis.⁵ There’s even a clinical name for the trap, “diagnostic overshadowing.” Once you carry a psychiatric label, every new symptom gets read as more psychiatry, and the hunt for a physical cause quietly stops.⁶

Worse yet, when you start in the wrong place, the massive engines of institutional healthcare can build momentum in the wrong directions, causing negative unintended consequences for patients far beyond the doctor’s office or therapist’s couch.

Why does this happen?

Wanting to understand this issue, my team and I did our best to map (computationally) the complex, intersecting healthcare systems around mental and physical health. What would it take for these issues to be detected? What’s working? What isn’t? Multiple distinct steps in the value chain (2,332 of them). Diagnostic tests, databases, clinical workflows, billing codes. Anything we could think of.

I expected the problem to live in the science. Was there a lack of diagnostic tests or other technology gaps causing misdiagnosed patients to slip through the cracks?

No, not really. The opposite turned out to be true. First of all, this is an old problem and pockets of researchers have looked at it over the decades. For example, in the late 1970s, researchers gave hundreds of psychiatric patients a careful medical workup and found that many of their “mental” symptoms were caused by underlying physical illnesses, and that nearly half of those illnesses had been sitting there undiagnosed.⁷ Half.

Follow-up research in a state hospital put the number even higher.⁸ That was almost fifty years ago. Today, by various counts, a physical exam happens for only a small fraction of psychiatric patients, and a large share of psychiatrists say they don’t feel competent to do one.⁹ It just isn’t something mental health practitioners routinely “do”.

Peeling back the layers, you don’t find a villain. It isn’t really about lazy or greedy therapists. Instead, you find a chain of barriers, each one individually sensible, that add up to a flawed system.

Three key systemic barriers came up in the analysis. They aren’t the “only” ones, but they kept bubbling to the top of the priority list. So, even with plenty of tests on shelves, and even if you can get mental health professionals to consider them, there are still some systemic bottlenecks that need to be unblocked before real progress can scale.

Systemic barriers, named

Medical record systems don’t have the data to train smarter software on. Modern medicine, at scale, increasingly runs on software that scans patient records and flags things worth a second look. The version of that software we’d need here would learn from past cases and flag where psychiatric symptoms might really be caused by a physical illness. The bottleneck is something called “labeled clinical data.” Patient records where a doctor has marked, in a way a computer can read, “this person’s psychiatric symptoms turned out to be caused by a physical illness,” with the lab work attached to prove it. If you wanted to build a tool that learns to flag “this depression feels like a thyroid problem,” you’d need thousands of past cases tagged exactly that way. They barely exist. There are a few hundred where you’d want hundreds of thousands. Here’s the vicious circle: we don’t look because nothing flags it, and nothing flags it because we never looked.

The medical knowledge exists but isn’t in a form software can act on either. Doctors already know the rules. Every guideline says some version of “rule out physical causes first.” That instruction lives in PDF documents and in the trained instincts of good doctors. Turning it into something the software can actually execute, a rule that quietly surfaces “check the thyroid” at the right moment, is a separate job that mostly hasn’t been done. The knowledge is real. It just hasn’t been translated into the language computers speak.

Now here’s the twist. A much simpler version of that prompt already exists. It isn’t smart. It doesn’t learn. It’s closer to a sticky note built into the order screen: when a doctor is about to prescribe an antidepressant, a small box pops up saying, “consider a thyroid test, consider a B12 test.” This feature already exists in most medical record systems.¹⁰ It’s just rarely switched on.

That's because, when it comes to hospital software, turning on any feature like this requires a committee. A hospital has to approve the alert, decide when it appears and who sees it, make sure it doesn’t become one more pop-up doctors learn to ignore, determine who can order the test and decide who’s responsible for following up on the result.¹¹

Why are these problems especially bad in mental health, specifically?

None of those three barriers is really about mental health. Encoding a guideline, training a tool on good records, switching on a prompt, those are hard everywhere in medicine. So why are they so much worse here?

The answer goes back to a decision made in 2009. When the government spent billions to drag American medicine into the digital age, it paid hospitals and doctors to adopt electronic records and left mental health and addiction facilities out of the deal.¹⁸ The money that wired up the rest of the system never reached them. Fifteen years later the gap is exactly where you’d expect.

A real share of mental health facilities still can’t order a lab test through their own software, and most don’t connect to the networks that let one provider see another’s results.¹⁸ I can’t prove that single decision is why the man with Wilson’s went thirteen years without the right blood test. It’s hard not to see the link though. The ordinary frictions of medicine land on the one part of the system that was never handed the tools to absorb them. The place we most need someone to look for a physical cause is the place least equipped to do it.

Is it too expensive?

The research on routine testing is mixed. Test every patient for everything and most results will come back normal. That gets expensive quickly.¹² Nobody is suggesting that. Testing makes more sense when something doesn’t fit, or when a patient isn’t getting better with treatment.¹³ The man with Wilson’s disease kept getting worse for thirteen years. At some point, that should have raised the possibility that the original diagnosis was wrong.

Ordering a blood test is more expensive than not ordering one. True. It’s also much cheaper than a decade of misdiagnosis and failed therapies.

The same failure, in plain sight

People with serious mental illness who take antipsychotic drugs are supposed to get routine blood tests for things like blood sugar and cholesterol. The guidelines are clear about this. Still, the testing often doesn’t happen. People with serious mental illness die at more than twice the rate of the general population, and roughly two-thirds of those excess deaths are from medical causes rather than the mental illness itself.¹⁴ The gap in life expectancy is getting wider, not narrower.¹⁵

One group of researchers tried something remarkably simple. They actually did add a reminder to the medical record software and gave their staff some basic education. As a result, monitoring rose from about a third of patients to about half, and the improvement lasted for more than two years.¹⁶ They didn’t need a new test or a new technology. They changed the workflow.

We found something similar with regulation. Our analysis initially flagged tighter federal rules for certain lab tests as a potential barrier. While we were doing the work, a court struck the rule down and the FDA withdrew it.¹⁷ One potential barrier disappeared. The testing problem didn’t.

What's left is much more basic: missing records, incomplete data, unclear procedures and approvals that take time. None of these problems is especially dramatic. Together, they can determine whether a test that already exists actually gets used.

What it looks like when it works

None of this requires a scientific breakthrough. We just need to make someone responsible for checking and follow up to make sure it happens.

England offers a useful example. Since 2006, the National Health Service has paid family doctors to give people with serious mental illness an annual physical health check, including weight, cholesterol, blood pressure, blood sugar and alcohol use.¹⁹ More than half a million people are covered. When the checks were removed from the payment program, the number of people receiving them fell within a year. When they were added back, it rose again.¹⁹ The test didn’t change. The incentive to make sure it happened did.

There’s a limit to what this accomplishes. The same research found that the checks improved detection more than treatment. Doctors were more likely to find high cholesterol or high blood sugar, but patients didn’t always receive better treatment once those problems were found.¹⁹ Finding the problem is only the first step. It’s still a step we have to take.

The same pattern shows up in the United States. Programs that put a mental health clinician directly into the primary care team, an approach supported by dozens of trials, get people diagnosed and into treatment faster than usual care.²⁰ Again, the technology isn’t what changed. Someone was given responsibility for making sure the problem was found and addressed.

What he needed

The man with Wilson’s spent thirteen years being treated for the wrong illness, while the test that could have identified the right one was available all along.

His case was eventually solved because someone asked whether his psychiatric symptoms might have a physical cause. That worked for him. It’s a terrible system for everyone else. At scale, you can’t depend on the right thought occurring to the right person at the right moment.

That’s what makes his story hard to shake. He didn’t need a medical breakthrough. He needed someone to order a blood test that had been available for decades. Thirteen years is a long time to wait for something medicine already knew how to do.

Endnotes

1. Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, leading to copper accumulation in the liver, brain, and other organs. See Merck Manual Professional Edition, “Wilson Disease.” The case described here is drawn from F. R. Bhatti and S. Liaqat, “Mental or Metabolic?: Misdiagnosis of Wilson Disease as Primary Psychiatric Disorder in Multiple Members of a Pakistani Family,” European Psychiatry 68 (2025), DOI 10.1192/j.eurpsy.2025.1222.

2. Diagnosis typically combines a slit-lamp eye examination for Kayser-Fleischer rings (copper deposits in the cornea) with a serum ceruloplasmin blood test and 24-hour urinary copper. See Merck Manual Professional Edition, “Wilson Disease”; and “Kayser-Fleischer Ring,” StatPearls (NCBI Bookshelf), 2024.

3. Bhatti and Liaqat, “Mental or Metabolic?” (2025). Case 1: a 32-year-old man carrying diagnoses of treatment-resistant schizophrenia and obsessive-compulsive disorder for 13 years, whose symptoms worsened despite extensive psychiatric treatment until an underlying metabolic cause was investigated. Case 2: his 16-year-old brother, initially attributed to academic stress. Case 3: their mother, who developed major depressive disorder with psychosis.

4. Wilson's disease has an estimated prevalence of roughly 1 in 30,000. See “Wilson's Disease / Kayser-Fleischer Ring,” EyeWiki (American Academy of Ophthalmology).

5. Numerous medical disorders produce symptoms that mimic psychiatric conditions, including thyroid disease (depression) and autoimmune encephalitis (psychosis). See Merck Manual Professional Edition, “Medical Assessment of the Patient With Psychiatric Symptoms,” 2026. The best-known popular account of autoimmune encephalitis misdiagnosed as psychiatric illness is Susannah Cahalan’s Brain on Fire: My Month of Madness (Free Press, 2012).

6. “Diagnostic overshadowing” refers to the misattribution of physical symptoms to a patient’s mental illness. See M. Shefer et al., “Diagnostic Overshadowing and Other Challenges Involved in the Diagnostic Process of Patients with Mental Illness Who Present in Emergency Departments with Physical Symptoms,” PLOS ONE (2014), PMC4219761.

7. R. C. W. Hall, M. K. Popkin, R. A. DeVaul, L. A. Faillace, and S. K. Stickney, “Physical Illness Presenting as Psychiatric Disease,” Archives of General Psychiatry 35, no. 11 (1978): 1315–1320, DOI 10.1001/archpsyc.1978.01770350041003. In 658 consecutive psychiatric outpatients, 9.1% had a medical disorder judged to be producing their psychiatric symptoms; 46% of those patients had medical illnesses previously unknown to them or their physician.

8. R. C. W. Hall, E. R. Gardner, S. K. Stickney, A. F. LeCann, and M. K. Popkin, “Physical Illness Manifesting as Psychiatric Disease: II. Analysis of a State Hospital Inpatient Population,” Archives of General Psychiatry 37, no. 9 (1980): 989–995, DOI 10.1001/archpsyc.1980.01780220027002. Of 100 patients intensively evaluated, 46% had medical illnesses judged to have caused or greatly exacerbated the symptoms responsible for admission, and 80% had a physical illness requiring treatment.

9. Surveys of psychiatric practice have reported that physical examinations are performed on a minority of psychiatric patients and that a substantial share of psychiatrists report not feeling competent to conduct one. See B. P. Sharma et al., “Physical Illnesses Among Psychiatric Outpatients in a Tertiary Care Health Institution,” PMC2913645, summarizing earlier survey findings that fewer than 35% of practicing psychiatrists routinely examined patients physically and that physical examination rates were as low as ~13% of inpatients and ~8% of outpatients.

10. Standards-based, in-workflow clinical decision support at the point of order entry (HL7 CDS Hooks “order-select” and “order-sign”) is documented and available within major U.S. electronic health record systems, including Epic. See the HL7 CDS Hooks specification and Epic developer documentation.

11. Local implementation of point-of-care decision support depends on institutional governance: multidisciplinary CDS committees, alert tuning to limit “alert fatigue,” and workflow approval. See ONC/ASTP SAFER Guides (Computerized Provider Order Entry with Decision Support), 2025.

12. Multiple studies and a meta-analysis have found limited yield from routine, untargeted laboratory “medical clearance” screening of psychiatric patients with normal history, vital signs, and physical exam. See S. Conigliaro et al., “Utility of Investigations, History, and Physical Examination in ‘Medical Clearance’ of Psychiatric Patients: A Meta-Analysis,” Psychiatric Services (2021), DOI 10.1176/appi.ps.202000858; and E. L. Anderson, K. Nordstrom, M. P. Wilson, et al., “American Association for Emergency Psychiatry Task Force on Medical Clearance of Adults Part I,” Western Journal of Emergency Medicine 18, no. 2 (2017): 235–242.

13. Clinical guidance recommends targeted medical workup when a psychiatric presentation is atypical or when symptoms fail to respond to, or worsen with, psychiatric treatment. See “Physical Exam in Psychiatry and ‘Medical Clearance,’” PsychDB; and Anderson et al., AAEP Task Force (2017).

14. All-cause mortality among people with serious mental illness is roughly 2 to 3.5 times that of the general population, and approximately two-thirds of the excess mortality is attributable to natural (medical) causes, particularly cardiovascular disease. See T. Soda et al., “Systematic Quality Improvement and Metabolic Monitoring for Individuals Taking Antipsychotic Drugs,” Psychiatric Services 72, no. 6 (2021): 647–653, DOI 10.1176/appi.ps.202000155; and “What Is Behind the 17-Year Life Expectancy Gap Between Individuals With Schizophrenia and the General Population?,” Schizophrenia (Nature) (2025), DOI 10.1038/s41537-025-00667-1.

15. The life-expectancy gap between people with severe mental illness and the general population persists and may be widening, largely because survival gains in the general population have not reached people with SMI. See “Contributions of Specific Causes of Death to Lost Life Expectancy in Severe Mental Illness,” European Psychiatry (2017), PubMed 28391102.

16. Soda et al., “Systematic Quality Improvement and Metabolic Monitoring” (2021). A combination of staff and patient education and an EHR-based reminder raised cardiometabolic monitoring (HbA1c and lipid panel) from 33% to 49% over one year, a gain sustained for 27 months after the intervention.

17. The FDA’s May 2024 final rule subjecting laboratory-developed tests to medical-device regulation was vacated by the U.S. District Court for the Eastern District of Texas on March 31, 2025 (American Clinical Laboratory Association v. FDA), and the FDA formally rescinded the rule on September 19, 2025. See U.S. Food and Drug Administration, “Laboratory Developed Tests,” fda.gov.

18. The 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act provided incentive payments for electronic health record adoption to hospitals and eligible physicians but excluded substance use and mental health treatment facilities; as the Office of the National Coordinator for Health IT (ONC/ASTP) notes, “as a result, EHR adoption and interoperability gaps persist.” In 2024, 68% of substance use and mental health facilities used EHRs only and 25% still used a mix of EHR and paper; among EHR-only facilities, 71% could order lab tests through the EHR (50% of hybrid facilities), and only 19% participated in a health information exchange. See ONC/ASTP, “Electronic Health Record Adoption and Exchange Capabilities Among Substance Use and Mental Health Treatment Facilities, 2024,” healthit.gov (data brief, April 2026), drawing on SAMHSA’s 2024 National Substance Use and Mental Health Services Survey (N-SUMHSS).

19. In England, the Quality and Outcomes Framework has incentivized general practitioners to perform annual physical health checks (including body mass index, cholesterol, blood pressure, blood glucose, and alcohol use) for patients with serious mental illness since 2006, covering more than 535,000 people. A difference-in-difference analysis of national primary care data found that removing checks from the incentive scheme reduced uptake of BMI, cholesterol, and alcohol checks by 14.3, 6.8, and 11.9 percentage points respectively, while reintroducing the BMI check raised its uptake by 10.2 percentage points. See M. A. Matias et al., “Assessing the Uptake of Incentivised Physical Health Checks for People with Serious Mental Illness: A Cohort Study in Primary Care,” British Journal of General Practice 74, no. 744 (2024): e449, DOI 10.3399/BJGP.2023.0532. A separate cohort study found the 2004 incentive produced sustained increases in the recording of elevated cholesterol (odds ratio 1.37), obesity (1.21), and hypertension (1.19) in the serious-mental-illness group, but found no clear effect on the prescribing of lipid-modifying or anti-diabetic medication, indicating incentives improved identification more than treatment. See “Financial Incentives and the Recording of Cardiovascular Risk Factors in Severe Mental Illness,” PMC5466340. Pay-for-performance evidence overall is mixed.

20. The Collaborative Care Model, which embeds behavioral health management within primary care, is supported by more than 80 randomized controlled trials. One review reports that patients in collaborative care reach a diagnosis and begin treatment within six months roughly 75% of the time, compared with under 25% in usual care. See “Collaborative Mental Health Care: A Narrative Review,” PMC9803502; and University of Washington AIMS Center materials on the Collaborative Care Model.