The “bible” of clinical psychiatry—the DSM, short for the Diagnostic and Statistical Manual of Mental Disorders—is one of the most popular psychiatry reference books around the world. Clinicians use it to diagnose patients and scientists use it to guide research.
Despite its wide impact, the DSM has never integrated biology in its diagnoses of mental illness. This omission was largely because the underlying biology of mental illness was too preliminary to be included in such a widely used clinical manual.
The most recent version of the DSM—the DSM-5, released in 2013—has attracted significant criticism from clinicians and researchers, including on how its lack of objective biological measures risks medicalizing human suffering and reducing the validity of psychiatric diagnoses.
The American Psychiatric Association announced that it will release the next edition of the DSM in the coming years, and one of its major plans is to modernize the manual by introducing biology. I was a member of the DSM’s strategic committee between May 2024 and August 2026 and contributed to the subcommittee tasked with integrating neurobiology into the manual.
Researchers’ understanding of the biology of mental disorders is still slowly evolving. So my DSM colleagues and I decided to take a more nuanced approach to incorporate neurobiology into the diagnosis of psychiatric conditions.
What are biomarkers?
Biological factors are mechanisms that may be involved in the development of a disease but have not yet crystallized into something that can be quantifiably measured in the lab. These factors can be physiological, genetic, or biochemical.
In contrast, biological markers—called biomarkers for short—are characteristics that can be objectively measured and used to evaluate a biological process, including how well someone is responding to a particular treatment. Biomarkers can be collected through blood tests, imaging scans, and other methods that reveal factors associated with a specific disease.
Biomarkers are widely used in medicine. For example, hemoglobin A1C levels are used to diagnose and monitor diabetes, cholesterol levels to determine cardiovascular risk, and CT scans to measure the size of a tumor.
Why aren’t there biomarkers for mental illness?
There are currently no scientifically valid biomarkers for any psychiatric condition, with the exception of certain proteins used to diagnose Alzheimer’s disease. The primary reason for this chasm between psychiatry and the rest of medicine is that knowledge about the biological basis of mental disorders lags behind other medical disorders.
The biological changes underlying mental illness are subtle, and current technologies are unable to easily capture them. Serious mental illnesses are, at their core, brain disorders with significant psychological and social components. Having a family history of mental illness and trauma are primary risk factors for major mental disorders. These strong environmental influences make it challenging to precisely separate the influences that biological factors and psychosocial considerations have on mental illnesses.
In addition, researchers conceptualize psychiatric disorders not as discrete illnesses but behavioral syndromes: a constellation of signs and symptoms that overlap each other. For example, anxiety and mood disorders have overlapping signs and symptoms, and patients often meet criteria concurrently for both sets of disorders. The same is true of schizophrenia and bipolar disorder with psychosis.
Characterizing each of these disorders as discrete conditions in the DSM is an oversimplification because they cluster together due to shared genetic and environmental factors. Further, conditions such as major depressive disorder and schizophrenia likely have several subgroups that superficially resemble each other but develop through different mechanisms and pathways. Finding a single biomarker that reflects multiple processes at the same time is unrealistic.
Syndromes have long existed in medicine. Diseases such as tuberculosis, cancer, and diabetes were recognized as clusters of symptoms and signs before advances in science and technology could pinpoint the biological mechanisms that cause each disease.
But researchers haven’t reached that juncture with mental illnesses. Nobel Prize-winning psychiatrist and neurobiologist Eric Kandel famously wrote that “the last frontier of the biological sciences … is to understand the biological basis of consciousness and the mental processes by which we perceive, act, learn, and remember.” He believed that solving this “ultimate challenge” requires merging cell biology with psychology to explain human behavior and consciousness in purely biological terms.
Advances in neurobiology
Although research is ongoing, there have been meaningful advances in the neurobiology of mental health since the publication of the fifth version of the DSM. I believe three advances seem particularly promising.
The first are biomarkers for Alzheimer’s disease. Until recently, diagnosing Alzheimer’s required a medical history and exam as well as postmortem evidence of two abnormal proteins associated with the disease called amyloid and tau. In March 2025, the Food and Drug Administration approved a blood test to detect specific forms of these proteins and help confirm a diagnosis of Alzheimer’s. This is the first instance of a biomarker for a disorder that affects both the brain and behavior.
The second are immune factors. The immune system has been implicated in several medical conditions, including mood disorders such as depression. For example, C-reactive protein is a molecule that the liver makes in response to injury and infection. Approximately 30 percent of patients with depression have high CRP levels, suggesting that it may serve as a biomarker to identify a subtype of patients who may respond better to certain types of treatment than those with lower levels of CRP.
The third are genetic risk factors. Certain genes are associated with an increased risk of developing a mental disorder. These risk genes are different from disease genes, which directly cause a disorder. Researchers have linked multiple risk genes to several mental disorders, and the effect each genetic variant has on developing a mental disorder is cumulative. Bundling these individual genetic variants into what’s called a polygenic risk score could offer a more comprehensive estimate of disease risk.
While genetic biomarkers are not ready for use in the clinic, integrating genetic and psychosocial risk factors can help psychiatry transition into the era of precision medicine.
Future of DSM
In 2013, psychiatrist Henry Nasrallah conducted an online survey of colleagues visiting the webpage of the journal Current Psychiatry, of which he was editor-in-chief. He wrote that 65 percent of respondents predicted the DSM-6 will include laboratory tests to diagnose psychiatric disorders and that he believed they might be right.
Thirteen years later, researchers are finally working to introduce biology to the DSM, one finding at a time.
The DSM isn’t perfect, but it offers a common language and conceptual framework for mental health clinicians to help support patients and their families over the long haul of mental illness.
While science reveals the inconvenient truth about how complex mental disorders are, I believe incorporating neuroscience into the DSM as the research advances will provide clinicians a more scientific and broader perspective on mental health. One day, patients may be able to walk into the clinic with results from genetic tests, brain scans, and blood work that their health team can use to provide more precise diagnoses and personalized treatment.
That’s the dream I have for the future of psychiatry.
