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

Catalina Mourgues-Codern; David Benrimoh; Jay Gandhi; Emily A Farina; Raina Vin; Tihare Zamorano; Deven Parekh; Ashok Malla; Ridha Joober; Martin Lepage; Srividya N Iyer; Jean Addington; Carrie E Bearden; Kristin S Cadenhead; Barbara Cornblatt; Matcheri Keshavan; William S Stone; Daniel H Mathalon; Diana O Perkins; Elaine F Walker; Tyrone D Cannon; Scott W Woods; Jai L Shah; Albert R Powers

doi:10.1016/j.biopsych.2025.02.891

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

Biol Psychiatry. 2025 Feb 26:S0006-3223(25)00990-4. doi: 10.1016/j.biopsych.2025.02.891. Online ahead of print.

Authors

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
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.