Emergence and Dynamics of Delusions and Hallucinations Across Stages in Early Psychosis

Catalina Mourgues-Codern¹, David Benrimoh², Jay Gandhi¹, Emily A Farina¹, Raina Vin³, Tihare Zamorano⁴, Deven Parekh⁴, Ashok Malla⁴, Ridha Joober⁴, Martin Lepage⁴, Srividya N Iyer⁴, Jean Addington⁵, Carrie E Bearden⁶, Kristin S Cadenhead⁷, Barbara Cornblatt⁸, Matcheri Keshavan⁹, William S Stone⁹, Daniel H Mathalon¹⁰, Diana O Perkins¹¹, Elaine F Walker¹², Tyrone D Cannon¹³, Scott W Woods¹, Jai L Shah⁴, Albert R Powers¹⁴

Affiliations

¹ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Connecticut Mental Health Center, New Haven, Connecticut.
² Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
⁴ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁵ Department of Psychiatry, University of Calgary, Hotchkiss Brain Institute, Calgary, Alberta, Canada.
⁶ Departments of Psychiatry and Biobehavioral Sciences & Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
⁷ Department of Psychiatry, University of California San Diego, La Jolla, California.
⁸ Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
⁹ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of California San Francisco and Weill Institute for Neurosciences, San Francisco, California; Veterans Affairs Health Care System, Mental Health Service 116D, San Francisco, California.
¹¹ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹² Departments of Psychology and Psychiatry, Emory University, Atlanta, Georgia.
¹³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.
¹⁴ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Connecticut Mental Health Center, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut. Electronic address: albert.powers@yale.edu.

PMID: 40020853
PMCID: PMC12353309 (available on 2026-02-26)
DOI: 10.1016/j.biopsych.2025.02.891

Emergence and Dynamics of Delusions and Hallucinations Across Stages in Early Psychosis

Catalina Mourgues-Codern et al. Biol Psychiatry. 2025.

. 2025 Feb 26:S0006-3223(25)00990-4.

doi: 10.1016/j.biopsych.2025.02.891. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Connecticut Mental Health Center, New Haven, Connecticut.
² Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
⁴ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁵ Department of Psychiatry, University of Calgary, Hotchkiss Brain Institute, Calgary, Alberta, Canada.
⁶ Departments of Psychiatry and Biobehavioral Sciences & Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
⁷ Department of Psychiatry, University of California San Diego, La Jolla, California.
⁸ Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
⁹ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of California San Francisco and Weill Institute for Neurosciences, San Francisco, California; Veterans Affairs Health Care System, Mental Health Service 116D, San Francisco, California.
¹¹ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
¹² Departments of Psychology and Psychiatry, Emory University, Atlanta, Georgia.
¹³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.
¹⁴ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Connecticut Mental Health Center, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut. Electronic address: albert.powers@yale.edu.

PMID: 40020853
PMCID: PMC12353309 (available on 2026-02-26)
DOI: 10.1016/j.biopsych.2025.02.891

Abstract

Background: Hallucinations and delusions are often grouped together as positive symptoms of psychosis. However, recent evidence suggests that they may be driven by distinct computational and neural mechanisms. Examining the time course of their emergence may provide insights into the relationship between these underlying mechanisms.

Methods: Participants from the second (N = 719) and third (N = 699) iterations of the North American Prodrome Longitudinal Study (NAPLS 2 and 3) were assessed for timing of clinical high risk for psychosis (CHR-P)-level delusion and hallucination onset. Pre-onset symptom patterns in patients with first-episode psychosis from the Prevention and Early Intervention Program for Psychosis (PEPP-Montréal) (N = 694) were also assessed. Symptom onset was determined at the baseline assessment, and the evolution of symptom patterns was examined over 24 months.

Results: In all 3 samples, participants were more likely to report the onset of attenuated/subthreshold delusions prior to attenuated/subthreshold hallucinations (odds ratios [ORs]: NAPLS 2 = 4.09; NAPLS 3 = 4.14; PEPP, z = 7.01, p < .001) and to present with only attenuated/subthreshold delusions compared with only attenuated/subthreshold hallucinations (ORs: NAPLS 2 = 5.6; NAPLS 3 = 11.11; PEPP = 42.75). The reemergence of attenuated/subthreshold delusions after remission was also more common than reemergence of attenuated/subthreshold hallucinations (ps < .05), which more often resolved first (ps < .001). In both CHR-P samples, ratings of delusional ideation decreased with the onset of attenuated hallucinations (p = .007).

Conclusions: Attenuated/subthreshold delusions tend to emerge before attenuated/subthreshold hallucinations and may play a role in their development. Future work should examine the relationship between the mechanisms that drive these symptoms and its utility for diagnosis and treatment.

Keywords: Clinical high risk; Delusions; First-episode psychosis; Hallucinations; Prodrome.

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Conflict of interest statement

Financial Disclosures

DB is a shareholder and founder of Aifred Health, a digital mental health company not involved in the current work. ML reports grants from Roche Canada, grants from Otsuka Lundbeck Alliance, grants and personal fees from Janssen, and personal fees from Otsuka Canada, Lundbeck Canada, and Boehringer Ingelheim outside the submitted work. SW reports that he has received speaking fees from the American Psychiatric Association and from Medscape Features. He has been granted US patent no. 8492418 B2 for a method of treating prodromal schizophrenia with glycine agonists. He is a consultant to and is a partner and owns stock in NW PharmaTech. All other authors report no biomedical financial interests or potential conflicts of interest.

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Emergence and Dynamics of Delusions and Hallucinations Across Stages in Early Psychosis

Affiliations

Emergence and Dynamics of Delusions and Hallucinations Across Stages in Early Psychosis

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources