Amanda Miller was 30 and pregnant with her second child in Hershey, Pennsylvania, when she developed depression. Following the birth, her depression worsened and was accompanied by a range of unexplained health problems.
Miller, a neuroscientist, said she consulted several psychiatrists and received prescriptions for multiple medications. Over two years, she tried four antidepressants and two antipsychotics. None helped — until her primary care physician noticed high levels of an autoimmune marker in her blood.
A specialist then ran “every test in the book,” Miller said. Eventually, she was diagnosed with the autoimmune disease lupus and prescribed an anti-inflammatory steroid. Some of her symptoms improved within hours. Her depression subsided not long after.
“I was convinced it was a placebo effect,” Miller said, “but then it kept working.”
Had inflammation been contributing to her mental health problems all along? Miller thinks so, although she cannot know for sure. Her psychiatrists never raised that possibility, she said.
In most medical specialties, physicians can confirm whether to pursue a type of treatment through tests such as blood work, imaging, and biopsies. Mental illnesses, however, have historically been diagnosed based on outward symptoms. That may change.
The American Psychiatric Association in a January paper included ideas for how it might incorporate biomarkers — biological indicators of mental illness that could appear on diagnostic tests — into future versions of its Diagnostic and Statistical Manual of Mental Disorders.
The DSM, sometimes called “psychiatry’s bible” because of its influence in the field, provides criteria for diagnoses. It is used by clinicians assessing patients and by insurance companies deciding whether to cover care.
‘Coordinated’ Research Needed
Psychiatric biomarkers are not ready for widespread use yet, the paper emphasized. Scientists have researched the topic for decades, with limited clinical application to date. More research is needed to prove these metrics are valid and reliable enough for use in patient care, the APA’s paper said, and other researchers have raised questions about how their use could affect health care costs, insurance coverage, and patient privacy.
Adding biomarkers to the DSM would be “a very big deal,” said Jonathan Alpert, an author of the January paper and vice chair of the APA’s Future DSM Strategic Committee.
Access to test results, along with symptoms, could streamline insurance coverage decisions and help clinicians make faster and more accurate diagnoses and treatment recommendations, he said. If patients’ biology suggests they would respond better to one treatment than another, their physician could begin that approach without delay.
Currently, prescribing psychiatric medications can be “a bit of a crapshoot,” with clinicians unable to predict whether they will work for a particular patient, said Matthew Eisenberg, director of the Center for Mental Health and Addiction Policy at the Johns Hopkins University Bloomberg School of Public Health.
In a seminal early-2000s trial funded by the National Institute of Mental Health, about 30% of participants with depression saw symptoms disappear with their first antidepressant treatment. That study remains one of the most robust antidepressant trials conducted, although researchers have more recently argued that fewer patients are cured by these medications than its results suggest.
Such a trial-and-error approach can lead to ineffective and unnecessary prescriptions, a topic of attack by proponents of the Make America Healthy Again movement, spearheaded by Health and Human Services Secretary Robert F. Kennedy Jr. Kennedy has been especially critical of antidepressants, having linked them to violence after a mass shooting without evidence and blaming physicians for overprescribing medications for pediatric patients.
HHS is analyzing psychiatric diagnosis and prescription trends and evaluating alternative mental health treatment approaches, with a particular focus on pediatric patients, spokesperson Emily Hilliard said in a statement. Hilliard did not respond to a question about Kennedy’s previous comments.
Biomarkers are already used to guide treatment in other medical disciplines, such as oncology. Arizona, Georgia, Kentucky, Texas, and more than a dozen other states require insurers to cover such testing. Blood and imaging tests are now used to help diagnose Alzheimer disease as well.
The APA included in its article a variety of ways psychiatric biomarkers could be used in the future — such as testing for brain activity, genetic profiles, or immune markers associated with certain psychiatric conditions, including schizophrenia and substance use disorders.
In depression, for example, about a quarter of patients have elevated levels of an inflammatory protein, called C-reactive protein, that can be identified through a blood test. Research has shown that patients with high levels of this protein appear to respond better to medications that alter dopamine levels in the brain, rather than selective serotonin reuptake inhibitors (SSRIs), a common type of antidepressant. C-reactive protein still needs to be “robustly validated” as a biomarker, according to the APA’s paper, but it is among the most promising currently under investigation.
A “coordinated, well-funded” research effort is needed to achieve such validation, the APA wrote — a tenuous prospect following reductions in federal research funding.
The National Institute of Mental Health alone had at least 128 grants, worth nearly $173 million, canceled in 2025, according to a research letter in JAMA. Though some grants have since been restored, researchers relying on federal funding still fear their work is vulnerable to cuts.
“There’s a great need for continued, active funding of research related to mental health,” Alpert said, but scientists will have to grapple with “uncertainties of the funding landscape.”
Ripple Effects on Coverage, Costs
Health care costs tend to be higher among patients with poorly controlled mental illnesses, due to expenses such as hospital visits, outpatient appointments, and prescriptions. Some research suggests biomarker testing could save money by identifying effective treatments more quickly and avoiding some of these costs.
One modeling study estimated that testing for genetic components that may influence a drug’s effectiveness could save the Canadian health system $956 million over 20 years if used among patients with major depression in British Columbia. Another study by Spanish researchers found that such testing reduced costs for most of the 188 participants with serious mental illness.
Whether the same would be true in the US health care system is unknown. In the short term, Johns Hopkins’ Eisenberg said an approach that uses biomarkers could raise health care spending due to testing costs.
Insurers may decline to cover expensive biomarker tests, he added. “It takes a while for new science to be proven safe and effective,” Eisenberg said. “And once it is, insurance companies don’t cover it immediately.”
Some researchers have raised concerns that insurers or employers could discriminate against people whose biological profiles suggest they are at risk of developing serious neuropsychiatric conditions.
It is a “critical moment” to consider legislative approaches to protect patients and train clinicians on appropriate use of these tools, said Gabriel Lázaro-Muñoz, a member of Harvard Medical School’s Center for Bioethics.
“I do not think that the field of psychiatry is currently ready to manage this,” he said.
The mental health system is not ready to “jump in with both feet,” said Andrew Miller, a professor of psychiatry and behavioral sciences at the Emory University School of Medicine who studies inflammation-related depression. But the APA’s embrace of biomarkers signals “the beginning of a revolution,” he said.
“This is a recognition … that what we’ve done up to this point has not been good enough,” Miller said. “And we can do better.”
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