Evidence map›Paper›PMID 26651391›Full record

ArticleThe American journal of psychiatry2016

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.

Brett A Clementz, John A Sweeney, Jordan P Hamm, Elena I Ivleva, Lauren E Ethridge, Godfrey D Pearlson, Matcheri S Keshavan, Carol A Tamminga

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 397 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
397citing papers in PubMed, 7 pooled it
31.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

397 citing papers in PubMed, 7 syntheses or guidelines pooled it, 757 citations in OpenAlex.

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  11. Schizophrenia, variability, and the Anna Karenina principle.Psychiatry research. Neuroimaging · 2026
    Article
  12. Anomalous self-experiences in biotypes of psychosis.European archives of psychiatry and clinical neuroscience · 2026
    Article
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337 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Brett A ClementzFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
John A SweeneyFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Jordan P HammFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Elena I IvlevaFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Lauren E EthridgeFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Godfrey D PearlsonFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Matcheri S KeshavanFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
Carol A TammingaFrom the Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, Conn., and the Institute of Living, Hartford Hospital, Hartford, Conn.; and the Department of Psychiatry, Harvard Medical School, Boston.
University of Georgia · US

Funding

Bipolar & Schizophrenia Consortium for Parsing Intermediate PhenotypesR01MH077851 · NIMH · UT SOUTHWESTERN MEDICAL CENTER · PI TAMMINGA, CAROL A · 2007 to 2019
$7.8M
Bipolar & Schizophrenia Consortium for Parsing Intermediate PhenotypesR01MH077945 · NIMH · YALE UNIVERSITY · PI PEARLSON, GODFREY D · 2007 to 2019
$7.6M
Stability of Biotypes: a Longitudinal EvaluationR01MH078113 · NIMH · WAYNE STATE UNIVERSITY · PI KESHAVAN, MATCHERI S. · 2007 to 2019
$6.2M
Bipolar & Schizophrenia Consortium for Parsing Intermediate PhenotypesR01MH077852 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI THAKER, GUNVANT K · 2007 to 2010
$3.5M
Bipolar & Schizophrenia Consortium for Parsing Intermediate PhenotypesR01MH077862 · NIMH · UT SOUTHWESTERN MEDICAL CENTER · PI SWEENEY, JOHN A · 2007 to 2010
$3.1M
Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP)R01MH096913 · NIMH · UT SOUTHWESTERN MEDICAL CENTER · PI TAMMINGA, CAROL A · 2013 to 2015
$950k
NIMH NIH HHS MH-077851NIMH NIH HHS MH-077852NIMH NIH HHS MH-077862NIMH NIH HHS MH-077945NIMH NIH HHS MH-078113NIMH NIH HHS R01 MH077851NIMH NIH HHS R01 MH077852NIMH NIH HHS R01 MH077862NIMH NIH HHS R01 MH077945NIMH NIH HHS R01 MH078113NIMH NIH HHS R01 MH096913
6 · The paper itself

Abstract

objectiveClinical 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.

methodA 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.

resultsMultivariate 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.

conclusionsThese 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.

Indexed as

FamilyAcoustic StimulationAdultBipolar DisorderBrainCase-Control StudiesElectroencephalographyEvoked Potentials, AuditoryFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsPhenotypePsychotic Disorders

Identifiers

PMID26651391
PMCPMC5314432
OpenAlexW2190536949

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.