“Schizophrenia: One disease or hundreds of diseases?”

Schizophrenia is a heterogeneous disease. The symptoms, course and outcome vary widely among patients. Together with multiple etiologic factors and pathophysiologic mechanisms, the extreme heterogeneity of schizophrenia suggests that it is not one disease, but hundreds of diseases, explained experts at WCP 2022.

Schizophrenia is not one disease

Schizophrenia is characterized by extreme heterogeneity, said Professor Rajiv Tandon, Kalamazoo, MI, not only in symptoms among patients and within an individual patient over time, but also in course and outcomes.1

The extreme heterogeneity of schizophrenia1 suggests there are hundreds of schizophrenias

At least five dimensions of symptoms including negative symptoms, positive symptoms, motor symptoms, mood symptoms, and cognitive deficits,2 are produced by different brain circuitries and respond differently to antipsychotics,1 explained Professor Tandon.

In addition, hundreds of genes and a variety of environmental risk factors confer risk for schizophrenia.1

Schizophrenia is characterized by at least five dimensions of symptoms produced by different brain circuitries and responding differently to antipsychotics1,2

However, despite intense research over 50 years and the availability of powerful brain imaging and investigative tools, understanding about schizophrenia is limited,1,4 said Professor Tandon. There is no diagnostic test or necessary or sufficient etiology or pathology for diagnosis.3

The multiple etiologic factors for schizophrenia and pathophysiologic mechanisms together with the extreme heterogeneity of phenotype suggest that schizophrenia is not one disease, but instead there are hundreds of schizophrenias, concluded Professor Tandon.


Hundreds of genes and many environmental risk factors confer risk for schizophrenia1

Abandon or rescue the construct of schizophrenia?

Professor Wolfgang Gaebel, Düsseldorf, Germany, cautioned against abandoning the construct of schizophrenia for now, because there is no better alternative.2 The construct does not need to be rescued, he said, but needs to transition to data-driven construct(s). Professor Gaebel outlined steps to achieve this including:

The current construct of schizophrenia needs to transition to data-driven construct(s)

  • Implementing the International Classification of Diseases 11th Revision5 (ICD-11) globally and harmonizing with The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition6 (DSM-5)
  • Keeping the concept and name “primary psychoses”
  • Involving people with lived experience

New constructs should be developed including fluid neuromental constructs instead of subtypes

  • Dialogue with industry on selective treatments, e.g., for positive and negative symptoms
  • Intensifying global research collaborations using an innovative, data-driven, bio-psychosocial, multi-level approach and encouraging the development of new constructs including fluid neuromental constructs instead of subtypes

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


  1. Keshavan MS, Nasrallah HA, Tandon R. Schizophrenia, "Just the Facts" 6. Moving ahead with the schizophrenia concept: from the elephant to the mouse. Schizophr Res. 2011;127(1–3):3–13.
  2. Gaebel W, Kerst A. The debate about renaming schizophrenia: a new name would not resolve the stigma. Epidemiol Psychiatr Sci 2019;28:258–61.
  3. Hany M, Rehman B, Azhar Y, Chapman J. Schizophrenia. 2022 May 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30969686.
  4. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, "just the facts" what we know in 2008. 2. Epidemiology and etiology. Schizophr Res. 2008;102(1-3):1–18.
  5. World Health Organization. International Classification of Diseases 11th Revision. Available at https://icd.who.int/en. Accessed 27 Sep 2022.
  6. American Psychiatric Association. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Available at https://psychiatry.org/psychiatrists/practice/dsm. Accessed 27 Sep 2022.