Cited by 768Schizophrenia research and treatmentMental Health and PsychiatryBipolar Disorder and Treatment

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Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

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Clementz, Brett A., Sweeney, John A., Hamm, Jordan P., Ivleva, Elena I., Ethridge, Lauren E., Pearlson, Godfrey D., Keshavan, Matcheri S., Tamminga, Carol A.·2016·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2015.14091200PMC PMC5314432

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Abstract

OBJECTIVE: Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. METHOD: A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. RESULTS: Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. CONCLUSIONS: These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.

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Authors: Clementz, B. A., Sweeney, J. A., Hamm, J. P., Ivleva, E. I., Ethridge, L. E., Pearlson, G. D., Keshavan, M. S., & Tamminga, C. A.
Affiliations: Hartford Hospital (US)
ORCID: Clementz, Brett A.
Sweeney, John A.
Hamm, Jordan P.
Ivleva, Elena I.
Ethridge, Lauren E.
Pearlson, Godfrey D.
Keshavan, Matcheri S.
Tamminga, Carol A.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2016-04-01
Volume: 173
Issue: 4
Pages: 373-384
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2015.14091200
PMC: PMC5314432
OpenAlex: W2190536949
Cited by: 768
References: 50
Citations by year: 2026: 64 · 2025: 59 · 2024: 58 · 2023: 61 · 2022: 70 · 2021: 78 · 2020: 72 · 2019: 122 · 2018: 68 · 2017: 75 · 2016: 40
FWCI: 49.56
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH077852, MH‐077945, MH 077852, R01MH077851, MH-078113, MH077851, R01MH096913, MH‐077862, R01MH078113, R01MH077862, R01MH077945)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords: schizophrenia, schizoaffective disorder, taxometric analysis, neuropsychological assessment, stop-signal task, auditory stimulation, first-degree relatives, social functioning, structural MRI
MeSH terms: Acoustic Stimulation, Adult, Bipolar Disorder, Brain, Electroencephalography, Evoked Potentials, Auditory, Family, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Phenotype, Psychotic Disorders, Saccades, Schizophrenia, Schizophrenic Psychology, Case-Control Studies, Young Adult

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Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

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