Rethinking Psychiatric Nosology: A Shift Towards Clinicopathological Approaches

Exploring the Future of Psychiatry

Over the past few months, three articles in the Psychiatric Times by Nassir Ghaemi, MD, and Mark Ruffalo, MSW, DPsa have presented intriguing ideas about the diagnostic foundation of our specialty. They argue that significant changes are needed in how we approach psychiatric diagnoses (see The Concept of Mental Illness and Why the DSM Approach Is Wrong, Psychiatric Times 12/3/25; What Happened to Psychopathology, 12/5/26; Diagnostic Validators and the Question of What Really Exists, 3/23/26).

These articles sparked my curiosity about what psychiatry might look like if we made major changes to nosology in the near future. How would this affect our relationship with the ICD, payment systems for services, and treatment options? Lacking the expertise to form a coherent vision of these changes, I decided to consult my friend, Chat-GPT. Here’s my query:

S. Nassir Ghaemi, MD, a Professor of Psychiatry at Tufts University School of Medicine, writes extensively about how the DSM's reliance on subjective distress and functional impairment diverges from scientific medicine’s clinicopathological approach to diagnosis. How would psychiatric nosology change if psychiatry adopted a clinicopathological approach to diagnosis? How would such a change impact the ICD? How would it affect insurance coverage for psychiatric disorders? How might it impact treatment?

And here’s Chat’s response, lightly edited for clarity:

What a Clinicopathological Approach Would Actually Mean

In scientific medicine, diagnoses are ideally based on:

• Etiology (cause)

• Pathophysiology (mechanism)

• Biomarkers or objective findings

• Course and prognosis

  
  

In psychiatry, diagnoses are largely:

• Syndromic (clusters of symptoms)

• Cross-sectional

• Validated by reliability rather than biological validity

  
  

A clinicopathological shift would require:

• Identifying biologically distinct disease entities

• Moving away from purely descriptive categories

• Replacing symptom thresholds with pathophysiologic subtypes

  
  

How Psychiatric Nosology Would Change

Fragmentation of Existing Disorders

Many existing disorders would likely fragment or disappear:

• “Major depressive disorder” could evolve into multiple biologically distinct subtypes.

• “Schizophrenia” might be viewed as a spectrum of different neurodevelopmental or neurodegenerative diseases.

• “Bipolar disorder” might survive intact due to a stronger biological signal, aligning with Emil Kraepelin’s longitudinal/course-based approach to diagnosis.

  
  

Rise of Biologically Anchored Subtypes

We could see the emergence of biologically anchored subtypes such as:

• “Inflammatory-mediated depression”

• “Glutamatergic dysregulation syndrome”

• “Synaptic pruning disorder with psychosis”

  
  

This resembles initiatives like the NIMH’s Research Domain Criteria.

Reduced Role of Distress and Impairment

Currently, a condition is not classified as a disorder unless it causes distress or impairment. In a clinicopathological model, a disease could exist regardless of whether it causes distress. Some psychiatric conditions might be diagnosed before subjective suffering emerges, similar to asymptomatic hypertension or early multiple sclerosis. Conversely, other conditions (e.g., mild anxiety) might not qualify as diseases at all.

Impact on the International Classification of Diseases

The ICD serves a broader global and administrative function than the DSM, so:

• The ICD would likely lag behind DSM shifts.

• A dual-track system may emerge:

- A clinical/pragmatic track (symptom-based, for global use)

- A research/biological track (for advanced systems)

• Eventually, we may see convergence if robust biomarkers emerge.

  
  

Impact on Insurance Coverage

In the current system (DSM/ICD-based), insurance relies on:

• Coded diagnoses

• Demonstrated distress or impairment

  
  

Under a clinicopathological model:

1. Some patients could lose coverage, such as those with distress but no identifiable pathology (e.g., adjustment reactions, mild anxiety, existential distress). These might be reclassified as “non-disease states” or non-reimbursable medical conditions.

2. Other conditions might gain earlier coverage, such as preclinical or biomarker-positive individuals. For example, “prodromal psychosis with neurobiological markers” could be recognized, paralleling pre-diabetes or early-stage cancer screening.

3. Greater stratification of reimbursement could occur, with treatments tied to specific mechanisms. Insurers may require biomarker confirmation or treatment matching.

   
   

Psychiatry currently captures a wide range of human suffering, but a clinicopathological shift might push some conditions into:

• Psychology

• Social services

• Coaching or non-medical care

  
  

Impact on Treatment

A. Instead of trial-and-error approaches with SSRIs and antipsychotics, we would see a move toward precision psychiatry:

• Mechanism-specific treatments

• Biomarker-guided prescribing

  
  

For example:

• Inflammatory depression could be treated with anti-inflammatory agents.

• Dopaminergic dysregulation might lead to targeted neuromodulators.

  
  

B. We would see fewer “broad-spectrum” diagnoses and generalized treatments:

• SSRIs might be used only in specific subtypes.

• Antipsychotics would be prescribed based on pathophysiology, not just symptoms.

  
  

C. Non-specific psychotherapy for biologically driven illnesses would likely decrease.

D. There would be an increased emphasis on longitudinal course:

• More focus on trajectory (as per Kraepelin)

• Less reliance on cross-sectional diagnosis

  
  

Conceptual and Philosophical Consequences

A. Psychiatry would become more “medical,” drawing closer to neurology and becoming less dependent on subjective reports.

B. However, this shift risks losing part of its domain:

• It could exclude meaningful suffering that lacks biomarkers.

• It might undermine psychiatry’s role as a bridge between medicine and the human condition.

  
  

Bottom Line: The Future of Psychiatry

If psychiatry adopted a clinicopathological model:

• Nosology would shift from syndromes to biologically defined diseases.

• DSM categories would fragment or disappear.

• The ICD would adapt slowly, likely maintaining dual systems.

• Insurance would become more biomarker-driven, potentially excluding some currently covered conditions.

• Treatment would become more precise, reducing trial-and-error methods.

• Psychiatry would gain scientific validity but risk narrowing its scope and abandoning parts of human suffering that are real but not (yet) biologically classifiable.

  
  

ChatGPT then contrasted Ghaemi’s position with another thinker in the field: Kenneth Kendler, MD, a professor at the Virginia Institute for Psychiatric and Behavioral Genetics:

—Ghaemi’s position is that psychiatry should approximate the rest of medicine. As previously noted:

• The DSM diagnoses are merely a collection of symptoms that lack validity as discrete diseases.

• ‘Distress/impairment’ is arbitrary and not a scientific criterion.

• Diagnosis should be based on etiology, pathology, and longitudinal course.

  
  

—Kendler, on the other hand, asserts that psychiatric diagnoses:

• Are multifactorial, bio-psycho-social constructs that can’t, as yet, be reduced to biological mechanisms.

• Though DSM diagnoses are imperfect, they provide useful constructs where ‘distress/impairment’ is a necessary feature.

• Psychiatry should embrace multiple explanations and not wait for pathological mechanisms that may never be discovered.

  
  

—In summary, Ghaemi is pushing psychiatry towards scientific purity and medical validity, while Kendler supports pragmatic pluralism that embraces imperfect categories as the best available tools.

Looking Ahead: The DSM-5-R and Beyond

Right on time, the March edition of the Psychiatric Times focused on where we should go from the DSM-5-R. An article by Awais Aftab, MD, clinical assistant professor at Case Western Reserve University, summarized significant proposed changes to the DSM. I encourage you to read the article, but I won’t repeat the changes here, except for one: the name of the DSM would change from Diagnostic and Statistical Manual to Diagnostic and Scientific Manual.

To me, ‘Scientific’ sounds aspirationally premature and pretentious, given the wide gulf between current practice and ‘scientific purity.’ Assuming that this controversy will linger for quite some time, why not simply leave the name as Diagnostic Manual of Psychiatry?

Jonathan Bauman, MD

June 2026

Dr. Bauman is an Emeritus ASAP Member and currently serves on the Board of The American Board of Adolescent Psychiatry (ABAP), hosted by ASAP, and is its newsletter Editor.