Evidence map›Paper›PMID 42025866›Full record

ArticleBiological psychiatry2026

Biophysical Modeling of Excitation/Inhibition Balance and Conversion to Psychosis in the Clinical High Risk Syndrome.

Julia Rodriguez-Sanchez, Daniel J Hauke, Dimitris A Pinotsis, Lioba C S Berndt, Hope Oloye, Spero C Nicholas, Holly K Hamilton, Brian J Roach, Peter M Bachman, Aysenil Belger and 15 more

Abstract read
PubMed Publisher
In one paragraph

Article in Biological psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Julia Rodriguez-SanchezHawkes Institute, University College London, London, United Kingdom; Department of Psychology and Neuroscience, City St. George's, University of London, London, United Kingdom. Electronic address: julia.sanchez.16@ucl.ac.uk.
Daniel J HaukeHawkes Institute, University College London, London, United Kingdom.
Dimitris A PinotsisDepartment of Psychology and Neuroscience, City St. George's, University of London, London, United Kingdom.
Lioba C S BerndtHawkes Institute, University College London, London, United Kingdom; Department of Psychology, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.
Hope OloyeHawkes Institute, University College London, London, United Kingdom; Institute of Cognitive Neuroscience, University College London, London, United Kingdom.
Spero C NicholasSan Francisco Veterans Affairs Health Care System, San Francisco, California; Northern California Institute for Research and Education, San Francisco, California.
Holly K HamiltonMinneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California.
Brian J RoachSan Francisco Veterans Affairs Health Care System, San Francisco, California; Northern California Institute for Research and Education, San Francisco, California.
Peter M BachmanDepartment of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts.
Aysenil BelgerDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Ricardo E CarriónNorthwell, New Hyde Park, New York; Institute of Behavioral Science, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, New York; Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
Erica DuncanAtlanta Veterans Affairs Health Care System, Decatur, Georgia; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Jason K JohannesenDepartment of Psychiatry, Yale University, School of Medicine, New Haven, Connecticut.
Gregory A LightDepartment of Psychiatry, University of California San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, La Jolla, California.
Margaret A NiznikiewiczDepartment of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston, Massachusetts; Veterans Affairs Boston Healthcare System, Brockton, Massachusetts.
Karl J FristonWellcome Trust Centre for Human Neuroimaging, Queen Square Institute of Neurology, University College London, London, United Kingdom.
Jean AddingtonHotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
Carrie E BeardenSemel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Psychology, University of California, Los Angeles, Los Angeles, California.
Kristin S CadenheadDepartment of Psychiatry, University of California San Diego, La Jolla, California.
Diana O PerkinsDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Elaine F WalkerDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Department of Psychology, Emory University, Atlanta, Georgia.
Scott W WoodsDepartment of Psychiatry, Yale University, School of Medicine, New Haven, Connecticut.
Tyrone D CannonDepartment of Psychiatry, Yale University, School of Medicine, New Haven, Connecticut; Department of Psychology, Yale University, New Haven, Connecticut.
Rick A AdamsHawkes Institute, University College London, London, United Kingdom; Institute of Cognitive Neuroscience, University College London, London, United Kingdom.
Daniel H MathalonSan Francisco Veterans Affairs Health Care System, San Francisco, California; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundReduced mismatch negativity (MMN) and P300 event-related potential (ERP) components are widely replicated in schizophrenia and are also observed in individuals at clinical high risk for psychosis (CHR-P) who subsequently convert to psychosis. It is unknown whether they reflect changes in excitatory and/or inhibitory synaptic function-both implicated in schizophrenia and considered potential drug targets.

methodsWe analyzed baseline MMN and P300 ERPs from the North American Prodrome Longitudinal Study (NAPLS 2) and asked whether altered synaptic excitation, inhibition, or both could explain amplitude reductions in CHR-P (n = 583). CHR-P participants who converted to psychosis (CHR-converters; n = 77) or remitted by the 24-month follow-up (CHR-remitters; n = 94) were compared on MMN evoked by pitch + duration double-deviant tones and P300 elicited by target tones from passive and active auditory oddball paradigms, respectively. Biophysical modeling was used to infer (excitatory) pyramidal cell and (inhibitory) interneuron function from both MMN and P300 ERPs.

resultsMMN and P300 amplitude reductions in future CHR-converters relative to CHR-remitters were best explained by reduced pyramidal cell excitability (posterior probability P > 0.95 of a group-by-condition interaction effect). In simulations, reduced pyramidal cell excitability suppressed deviant and target ERPs. Within CHR-converters, more severe positive symptoms were associated with disinhibition of pyramidal cells (P > 0.99).

conclusionsResults mirror previous findings in schizophrenia and suggest that reduced pyramidal cell excitability is present at baseline in future CHR-converters, consistent with the hypothesis that hypofunction of pyramidal cells is a primary pathology in schizophrenia rather than a consequence of chronic illness. Positive symptoms among CHR-converters may reflect compensatory downregulation of inhibition.

Indexed as

Biophysical modelingClinical high risk for psychosisDynamic causal modelingE/I balanceMMNP300

Identifiers

PMID42025866

What OpenQuestion holds

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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.