When you are given a psychiatric diagnosis, that label follows you. It shapes how doctors treat you, how insurers cover you, how family members understand you, and sometimes how you understand yourself. It determines the clinical trial you might qualify for, the medication you might be prescribed, and the research category your case gets filed under.
So it matters enormously whether those labels are accurate.
According to Dr. Bruce M. Cohen, Robertson-Steele Professor of Psychiatry at Harvard Medical School and Director of the Program for Neuropsychiatric Research at McLean Hospital, the answer for psychiatry’s most basic diagnostic categories is that they are mostly inaccurate. Evidence for this has been growing for decades.
In a wide-ranging interview published in Genomic Psychiatry in October 2025, Dr. Cohen shares five decades of intellectual and clinical experience, from his early days studying molecular genetics at MIT with Nobel laureates to his current work growing brain organoids from patient stem cells. He comes across as a scientist who has spent his career both building better science and questioning the foundations of his field.
The Moment That Started Everything
Dr. Cohen’s journey into psychiatry began with a single patient.
During his psychiatry clerkship as a medical student, which he had not especially looked forward to, he met a young woman who was agitated, delusional, and spoke in a way that was hard to follow. A few weeks later, after starting antipsychotic medication, she had changed into what he describes as “among the most rational and delightful people I have known.”
That transformation fascinated him. The diagnostic label she received, schizoaffective disorder, also caught his attention. To Dr. Cohen and his fellow students, it seemed less like a real category and more like a workaround, a mix of two existing labels used to explain symptoms that did not fit either one well. His discomfort with psychiatric diagnostic categories started then and, as he says, “became a recurring theme in my career.”
It was not an easy topic to pursue. When he was younger, a senior mentor warned him that publishing criticism of standard diagnostic models could end his career. He hesitated. It took him decades to return to the subject and publish openly about it. He counts this as one of his biggest regrets: that worries and institutional pressure kept important ideas from being shared for too long.
What the Science Actually Shows
The Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD), often called the twin bibles of psychiatric diagnosis, are built around categories. You either have schizophrenia or you do not. You either have bipolar disorder or you do not. These categories were mostly created by expert agreement about a century ago and have shaped psychiatric diagnosis ever since.
Dr. Cohen’s research, along with a growing body of work by others, strongly suggests that this architecture does not align with the underlying biology.
Psychiatric disorders such as schizophrenia and bipolar disorder are not single diseases with one cause. They are complex, shaped by many interacting genetic variants, developmental factors, environmental exposures, and random biological events. No two patients have the same mix of these factors, which is why two people with the same diagnosis can have very different symptoms, illness courses, and responses to treatment.
The evidence instead suggests that these conditions are better described by dimensions, which are measurable features that exist on a spectrum among people. Positive symptoms of psychosis include hallucinations and delusions. Negative symptoms include withdrawal and flat affect. Mood changes and cognitive changes are also important. These dimensions cross current diagnostic boundaries, appear in different combinations and severities, and more closely match clinical reality and biological findings.
This dimensional approach is not only appealing in theory but also useful in practice. Clinicians already use this way of thinking when they assess patients. Describing a patient’s unique mix of symptom dimensions provides much more information than a single label and helps create more meaningful patient groups for research.
Growing Brain Cells to Find the Answers
While questioning diagnostic models in clinical and academic literature, Dr. Cohen has also been building biological evidence in the lab using a technology that did not exist when he trained: induced pluripotent stem cells (iPSCs).
The concept is straightforward. A small sample of a patient’s blood or skin cells is reprogrammed into stem cells, which can become almost any cell type. These stem cells are then directed to become neurons, glial cells, and even three-dimensional brain organoids, tiny, living structures that have the same genetic makeup as the patient who gave the original sample.
This allows Dr. Cohen’s lab to study brain cells from people with schizophrenia, bipolar disorder, or late-onset Alzheimer’s disease. They are not using animal cells or cell lines from unrelated donors, but rather cells that carry the patients’ own genetic makeup. As he puts it, this technology is “giving us leads we did not have forty years ago.”
What these cells are showing matches the dimensional complexity Dr. Cohen supports in diagnosis. The lab has found that mitochondrial dysfunction and problems with energy metabolism are common markers across neuropsychiatric conditions. This matters because the brain is one of the body’s most energy-demanding organs, and problems with how its cells produce and use energy can affect communication, development, and resilience in many ways.
Importantly, these metabolic problems show up along with, not instead of, synaptic and neurotransmitter abnormalities. Several biological pathways are disrupted simultaneously, and their interactions affect the overall risk of disease. This is what you would expect from a complex condition, and it is something a single diagnosis cannot fully explain.
Dr. Cohen’s earlier research on antipsychotic drugs led to similar conclusions. His team found that a drug’s clinical strength was closely linked to how it spread in the brain, rather than to its affinity for any single receptor. All antipsychotic drugs, even those advertised as receptor-specific, interact with several receptors at the doses used in treatment. In other words, the way these drugs work is not as simple as blocking one pathway. It never was.
The Word “Schizophrenia” Should Go
One of Dr. Cohen’s most direct points in the interview is his call to replace the term “schizophrenia” completely. He calls it outdated, confusing, and negative, a word that brings stigma, hides biological complexity, and does not accurately describe what it is meant to name.
This is not a new idea. Japan formally replaced the term with “integration disorder” in 2002. South Korea followed. Several scientific advocacy groups have made similar recommendations. The argument is both scientific and humanitarian: a label that lumps together biologically diverse conditions under a single stigmatized name harms patients and impedes research.
Dr. Cohen imagines new terminology created with input from both clinicians and people who live with these conditions, whom he calls “consumers.” He believes these new terms should be based on a dimensional, evidence-based framework that is increasingly supported by data.
On Science, Institutions, and the Courage to Be Unconventional
A theme throughout the interview is the culture of science and how institutions can limit the kinds of thinking that move a field forward.
Dr. Cohen is open about the pressures he faced. He notes that research funding often goes to what he calls “next least step” research, meaning small, incremental work that builds on existing ideas rather than challenging them. New researchers and unconventional approaches are often at a disadvantage. Peer reviewers uphold the established consensus, and diagnostic manuals maintain expert authority.
He is not bitter about this. Instead, he is critical in the way a good scientist should be, using evidence and offering alternatives. During his eight years as President of McLean from 1997 to 2005, he turned around the hospital’s finances, reduced bureaucracy, and started more than 30 new clinical and research programs. He understands institutions from the inside.
His advice for the field is to take more risks on new people and ideas. He suggests considering different ways to understand what we know, replacing consensus-based diagnostics with evidence-based ones, and being willing to use accurate names, even if they are harder to say.
What This Means for Patients and Families
For anyone who has received a psychiatric diagnosis or seen a family member get one, Dr. Cohen’s work brings both challenges and hope.
Challenging, because it means the category you were given may not fully explain what is happening to you biologically, and treatments optimized for that category may not be optimized for you specifically.
Hopeful, because the research program he describes linking genetic variants to cellular biology to clinical presentation through dimensional frameworks points toward something better: understanding individual risk, identifying specific biological abnormalities that may be treatable, and potentially preventing illness in people who show early markers before symptoms fully emerge.
As he says, psychotic disorders rarely show up before adolescence, and dementias usually do not appear until old age. Prevention should be possible. The biology is becoming clearer. The tools are now available. What is needed is the will to use them and the courage to let evidence change the categories.