Although schizophrenia is the focus of the majority of research investigating psychosis, it represents only 30% of the poor outcome associated with the full spectrum of psychotic disorders, according to a 2018 paper by Guloksuz and van Os published in Psychological Medicine.1 This purported overemphasis on schizophrenia has led to a sort of tunnel vision in which the disease has become nearly synonymous with the concept of psychosis, limiting advancement in the area of psychotic disorders. 

The researchers suggest that the diagnosis of schizophrenia, which has been shown to have limited validity and specificity, be abandoned in favor of a broader approach. As an initial step toward reconceptualization, they propose a shift toward a classification system reflecting “single umbrella disorder – psychosis spectrum disorder (PSD) – with specifiers,” similar to autism spectrum disorder (ASD). “Even this subtle revision will help the field to rethink psychosis without the borders of schizophrenia and therefore clear the way for a better conceptualization in the future.”

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In a study published in the same issue of the journal, Zoghbi and Lieberman discourage the adoption of this system for various reasons.2 For example, they point to fundamental differences in ASD and PSD: “Unlike the syndrome of autism, psychosis is a transdiagnostic symptom that has psychiatric, neurologic, endocrine, infectious, and drug-induced etiologies,” they wrote. “Though psychosis exists on a continuum of severity, which makes the spectrum approach appealing, this does not necessarily mean that it is caused by the same underlying disease process.”

To further explore the implications of the PSD concept, Psychiatry Advisor interviewed Russell L. Margolis, MD, professor of psychiatry and neurology, and director of the Laboratory of Genetic Neurobiology, at Johns Hopkins University School of Medicine, and clinical director of the Johns Hopkins Schizophrenia Center.

Psychiatry Advisor: What are some of the proposed benefits of adopting “psychosis spectrum disorder” vs continuing to view schizophrenia as a distinct entity?

Dr Margolis: There is little question that the concept of schizophrenia is problematic. Among other problems, as Guloksuz and van Os point out, there is substantial etiologic and phenotypic overlap between schizophrenia and other disorders, particularly affective disorders. Hence, there is considerable appeal, and increasing scientific evidence, to postulate a regrouping of these disorders. Such a reorganization might indeed have considerable value for research.

Clinically, the potential is that better diagnostic schemes would yield diagnoses that correspond more tightly with treatment options and with long-term prognoses, and that would aid clinicians and their patients in understanding the particular illness of the patient. In other words, less struggle with fitting square pegs into round holes. 

Psychiatry Advisor: What are some of the potential drawbacks of doing so?

Dr Margolis: While generally correct that our current concepts of severe mental illness, including schizophrenia and affective disorders, need revision, the PSD proposed by Guloksuz and van Os is problematic. First, one aspect of the overlap among schizophrenia and affective disorders is “psychosis.” But here we run into problems. The term “psychosis” has multiple definitions and is not precisely defined by Guloksuz and van Os, and indeed is loosely used by clinicians and the public, creating confusion. Most broadly, often in slang use, psychosis is used to mean something like “very mentally ill.”

Somewhat less broadly, psychosis is used to describe a state in which there is loss of contact with reality. Sometimes it is used synonymously with schizophrenia. Most precisely, it refers to one of several psychopathologic symptoms: hallucinations, delusions, or disorganized patterns of thought and perhaps behavior. As such, psychotic phenomena are part of a large number of other disorders, as noted by Zoghbi and Lieberman (though one suspects that frequently reported phenomena, such as hearing voices, may actually reflect multiple different mental experiences depending on the underlying condition).

On the other hand, psychotic symptoms are only part of the problem faced by patients whom we now diagnosis with schizophrenia or an affective disorder, and a focus on such symptoms alone misses the clinical picture. As Zoghbi and Lieberman point out, the analogy that Guloksuz and van Os make between the  Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, concept of ASD and their concept of PSD is not quite correct, as the autism spectrum includes symptoms in a variety of domains that together make up the clinical syndrome of autism.   

Psychiatry Advisor: What are the relevant treatment implications for clinicians?

Dr Margolis: The clinical implications are that the use of PSD, as described by Guloksuz and van Os, will replace current confusion with new types of confusion and would not help to create diagnoses that clarify treatment options and improve prognostic accuracy. The fundamental problems of the Guloksuz and van Os PSD scheme are those faced by the Research Domain Criteria2,3 scheme:

  • confounding quantitative differences in symptoms with a spectrum of underlying disease entities
  • mistaking spectrum of disease variation with variations along a normal distribution in the population

Psychiatry Advisor: What should be next steps in terms of research on this topic?      

Dr Margolis: Research to improve our diagnostic system for schizophrenia, bipolar disorder, and related conditions should follow the bottom-up biomedical model that is slowly but surely improving our understanding of other complex diseases like cancer and the autoimmune diseases: Start with clinical syndromes; define etiologies, pathogenic pathways, and pathology; and then reiteratively refine the diagnostic categories. An example is dropsy (now known as edema), shown to be caused by a variety of very different disorders such as heart failure, liver failure, and renal failure, each of which could then be further defined into more and more specific conditions with more specific treatments.


1. Guloksuz S, van Os J. The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum. Psychol Med. 2018;48(2):229-244.

2. Zoghbi AW, Lieberman JA. Alive but not well: the limited validity but continued utility of the concept of schizophrenia. Psychol Med. 2018;48(2):245-246.

3. Insel T. Post by Former NIMH Director Thomas Insel: Research Domain Criteria – RDoC. National Institute of Mental Health. March 6, 2012. Accessed September 25, 2019.

This article originally appeared on Psychiatry Advisor