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Cited by 812Schizophrenia research and treatmentMental Health and PsychiatryNeural and Behavioral Psychology Studies

Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia

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Thompson, Paul M., Vidal, Christine, Giedd, Jay N., Gochman, Peter, Blumenthal, Jonathan, Nicolson, Robert, Toga, Arthur W., Rapoport, Judith L.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.201243998PMC PMC58784
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Abstract

Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks, as well as early (pre/perinatal) and late (usually adolescent) developmental brain abnormalities. With the use of brain mapping algorithms, we detected striking anatomical profiles of accelerated gray matter loss in very early-onset schizophrenia; surprisingly, deficits moved in a dynamic pattern, enveloping increasing amounts of cortex throughout adolescence. Early-onset patients were rescanned prospectively with MRI, at 2-year intervals at three time points, to uncover the dynamics and timing of disease progression during adolescence. The earliest deficits were found in parietal brain regions, supporting visuospatial and associative thinking, where adult deficits are known to be mediated by environmental (nongenetic) factors. Over 5 years, these deficits progressed anteriorly into temporal lobes, engulfing sensorimotor and dorsolateral prefrontal cortices, and frontal eye fields. These emerging patterns correlated with psychotic symptom severity and mirrored the neuromotor, auditory, visual search, and frontal executive impairments in the disease. In temporal regions, gray matter loss was completely absent early in the disease but became pervasive later. Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri, deficit regions found consistently in adult studies. These emerging dynamic patterns were ( i ) controlled for medication and IQ effects, ( ii ) replicated in independent groups of males and females, and ( iii ) charted in individuals and groups. The resulting mapping strategy reveals a shifting pattern of tissue loss in schizophrenia. Aspects of the anatomy and dynamics of disease are uncovered, in a changing profile that implicates genetic and nongenetic patterns of deficits.

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  • Childhood-onset schizophrenia, with a mean age of onset around the age of 10 years, is associated with a striking parietal GM loss, which progresses anteriorly during adolescence in a back-to-front fashion.

    “Childhood-onset schizophrenia, with a mean age of onset around the age of 10 years, is associated with a striking parietal GM loss, which progresses anteriorly during adolescence in a back-to-front fashion (52)”

    From Dynamic mapping of human cortical development during childhood through early adulthood (2004) · cites this paper as [52]

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Authors
Thompson, P. M., Vidal, C., Giedd, J. N., Gochman, P., Blumenthal, J., Nicolson, R., Toga, A. W., & Rapoport, J. L.
Affiliations
  • National Institutes of Health (US)
  • Laboratory of Neuro Imaging, Department of Neurology, Division of Brain Mapping, 4238 Reed Neurology, University of California School of Medicine, Los Angeles, CA 90095-1761; and Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1600
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2001-09-25
Volume
98
Issue
20
Pages
11650-11655
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.201243998
PMC
PMC58784
OpenAlex
W2062648684
Cited by
812
References
52
Citations by year
2026: 9 · 2025: 8 · 2024: 11 · 2023: 17 · 2022: 17 · 2021: 21 · 2020: 22 · 2019: 35 · 2018: 21 · 2017: 19 · 2016: 20 · 2015: 32 · 2014: 19 · 2013: 32 · 2012: 34
FWCI
24.87
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (RR13642)
  • National Institute of Mental Health (P20 MH/DA52176)
  • National Institute of Neurological Disorders and Stroke (NS38753, R01NS038753)
  • U.S. National Library of Medicine (LM/MH05639)
  • National Center for Research Resources (P41RR013642)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
very early onset schizophrenia, gray matter loss, adolescent brain development, cortical thinning, disease progression, parietal cortex, temporal lobe, dorsolateral prefrontal cortex, superior temporal gyrus, frontal eye field, psychotic symptom severity, neurodevelopmental model, brain mapping
MeSH terms
Adolescent, Alzheimer Disease, Brain, Brain Mapping, Follow-Up Studies, Humans, Intelligence, Magnetic Resonance Imaging, Reference Values, Schizophrenia, Schizophrenic Psychology, Time Factors, Age of Onset

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