CoChat
Sign Up
Cited by 600Schizophrenia research and treatmentPsychopathy, Forensic Psychiatry, Sexual OffendingNeural and Behavioral Psychology Studies

Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk

Open access
Cannon, Tyrone D., Chung, Yoonho, He, George, Sun, Daqiang, Jacobson, Aron, van Erp, Theo G.M., McEwen, Sarah, Addington, Jean +12 more·2015·Biological Psychiatry
DOI 10.1016/j.biopsych.2014.05.023PMC PMC4264996
Open this paper in CoChat — free account

Abstract

Background Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown. Methods In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms. Results In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma. Conclusions These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2014.05.023

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Schizophrenia is associated with accelerated gray matter loss in PFC, including loss of dendrites and spines in dlPFC.

    “Schizophrenia is associated with accelerated gray matter loss in PFC (Cannon, Chung, He, Sun, Jacobson, van Erp, & Consortium, 2014), including loss of dendrites and spines in the dlPFC (Glantz & Lewis, 2000).”

    From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Cannon et al., 2014

    The Discussion reports faster gray matter loss in prefrontal regions among clinical high-risk individuals who developed psychosis than among non-converters and healthy controls. That supports accelerated prefrontal loss around psychosis onset, but the study does not establish it for schizophrenia generally. The separate claim about dendrites and spines is attributed to Glantz and Lewis, not to this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • There is loss of dlPFC gray matter in schizophrenia and Alzheimer's disease, while changes in more ventral and medial PFC regions are evident in mood disorders and in post-traumatic-stress disorder (PTSD).

    “For example, there is loss of dlPFC gray matter in schizophrenia4,5 and Alzheimer’s disease6, while changes in more ventral and medial PFC regions are evident in mood disorders7 and in post-traumatic-stress disorder (PTSD)8.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [5]

    The paper reports that studies of early psychosis generally find lower dorsolateral prefrontal volumes, and its Results report prefrontal gray-matter loss in youth who convert to psychosis. That supports the regional-loss point, but its own longitudinal finding is in clinical-risk youth developing psychosis, not specifically patients diagnosed with schizophrenia. The Alzheimer’s, mood-disorder, and PTSD clauses have separate citations and are not attributed to this source. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The onset of schizophrenia is accompanied by increased signs of inflammation.

    “Indeed, the onset of schizophrenia is accompanied by waves of PFC gray matter loss, as well as increased signs of inflammation5.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [5]

    The Discussion (page unavailable) reports that higher baseline pro-inflammatory cytokine levels predicted steeper prefrontal thinning among clinically high-risk youth who developed psychosis. The Results, however, found no significant baseline difference in mean cytokine levels between converters, non-converters, and controls. The paper therefore links inflammatory markers to changes around psychosis onset, but does not show that signs of inflammation increase at the onset of schizophrenia. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The onset of schizophrenia is accompanied by waves of PFC gray matter loss.

    “Indeed, the onset of schizophrenia is accompanied by waves of PFC gray matter loss, as well as increased signs of inflammation5.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [5]

    The Discussion (page not available in our copy) reports steeper prefrontal gray matter loss in clinically high-risk youth who developed psychosis. It does not establish multiple “waves” of loss or limit the finding to the onset of schizophrenia specifically. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Guanfacine may offer a practical approach for reducing the inflammatory response and gray matter loss found in prodromal schizophrenia.

    “As guanfacine is approved by the US Food and Drug Administration for use in adolescents103, it may offer a practical approach for reducing the inflammatory response and gray matter loss found in prodromal schizophrenia5.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [5]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 2

  1. [10]Glausier JR Lewis DA 2012 Dendritic spine pathology in schizophrenia Neuroscience PMC3413758 22546337
  2. [27]First M Spitzer RL Gibbon M Williams B Williams JBW 1995 Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition New York Biometrics Research Department, New York State Psychiatric Institute

Cited by

Sorted by citations

Related

Authors
Cannon, T. D., Chung, Y., He, G., Sun, D., Jacobson, A., van Erp, T. G. M., McEwen, S., Addington, J., Bearden, C. E., Cadenhead, K., Cornblatt, B., Mathalon, D. H., McGlashan, T., Perkins, D., Jeffries, C., Seidman, L. J., Tsuang, M., Walker, E., Woods, S. W., & Heinssen, R.
Affiliations
  • Yale University (US)
  • University of California, Los Angeles (US)
  • University of Calgary (CA)
  • University of California San Diego (US)
  • Zucker Hillside Hospital (US)
  • University of California, San Francisco (US)
  • University of North Carolina at Chapel Hill (US)
  • Beth Israel Deaconess Medical Center (US)
  • Emory University (US)
  • National Institute of Mental Health (US)
Corresponding author
Cannon, Tyrone D.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2015-01
Volume
77
Issue
2
Pages
147-157
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2014.05.023
PMC
PMC4264996
OpenAlex
W2166663076
Cited by
599
References
63
Citations by year
2026: 28 · 2025: 28 · 2024: 38 · 2023: 49 · 2022: 44 · 2021: 73 · 2020: 73 · 2019: 78 · 2018: 38 · 2017: 43 · 2016: 54 · 2015: 44 · 2014: 8
FWCI
37.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Commonwealth of Massachusetts
  • National Institute of Mental Health
  • National Institutes of Health (MH081902, MH066160, MH081928, MH081857, MH082004, P50 MH080272, MH081988, P50 MH066286, MH082022, MH081984)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
clinical high risk for psychosis, transition to psychosis, cortical thickness, gray matter loss, schizophrenia pathophysiology, inflammatory cytokines, frontal cortex, prodromal symptoms, youth
MeSH terms
Adolescent, Cerebral Cortex, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Organ Size, Psychotic Disorders, Risk, Antipsychotic Agents, Reproducibility of Results, Cytokines, Disease Progression, Young Adult, Prodromal Symptoms

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review