Cited by 132Schizophrenia research and treatmentPsychopathy, Forensic Psychiatry, Sexual OffendingFunctional Brain Connectivity Studies

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Structural Brain Abnormalities in Youth With Psychosis Spectrum Symptoms

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Satterthwaite, Theodore D., Wolf, Daniel H., Calkins, Monica E., Vandekar, Simon N., Erus, Guray, Ruparel, Kosha, Roalf, David R., Linn, Kristin A., Elliott, Mark A., Moore, Tyler M., Hakonarson, Hakon, Shinohara, Russell T., Davatzikos, Christos, Gur, Ruben C., Gur, Raquel E.·2016·JAMA Psychiatry

DOI 10.1001/jamapsychiatry.2015.3463PMC PMC5048443

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Abstract

IMPORTANCE: Structural brain abnormalities are prominent in psychotic disorders, including schizophrenia. However, it is unclear when aberrations emerge in the disease process and if such deficits are present in association with less severe psychosis spectrum (PS) symptoms in youth. OBJECTIVE: To investigate the presence of structural brain abnormalities in youth with PS symptoms. DESIGN, SETTING, AND PARTICIPANTS: The Philadelphia Neurodevelopmental Cohort is a prospectively accrued, community-based sample of 9498 youth who received a structured psychiatric evaluation. A subsample of 1601 individuals underwent neuroimaging, including structural magnetic resonance imaging, at an academic and children's hospital health care network between November 1, 2009, and November 30, 2011. MAIN OUTCOMES AND MEASURES: Measures of brain volume derived from T1-weighted structural neuroimaging at 3 T. Analyses were conducted at global, regional, and voxelwise levels. Regional volumes were estimated with an advanced multiatlas regional segmentation procedure, and voxelwise volumetric analyses were conducted as well. Nonlinear developmental patterns were examined using penalized splines within a general additive model. Psychosis spectrum (PS) symptom severity was summarized using factor analysis and evaluated dimensionally. RESULTS: Following exclusions due to comorbidity and image quality assurance, the final sample included 791 participants aged youth 8 to 22 years. Fifty percent (n = 393) were female. After structured interviews, 391 participants were identified as having PS features (PS group) and 400 participants were identified as typically developing comparison individuals without significant psychopathology (TD group). Compared with the TD group, the PS group had diminished whole-brain gray matter volume (P = 1.8 × 10-10) and expanded white matter volume (P = 2.8 × 10-11). Voxelwise analyses revealed significantly lower gray matter volume in the medial temporal lobe (maximum z score = 5.2 and cluster size of 1225 for the right and maximum z score = 4.5 and cluster size of 310 for the left) as well as in frontal, temporal, and parietal cortex. Volumetric reduction in the medial temporal lobe was correlated with PS symptom severity. CONCLUSIONS AND RELEVANCE: Structural brain abnormalities that have been commonly reported in adults with psychosis are present early in life in youth with PS symptoms and are not due to medication effects. Future longitudinal studies could use the presence of such abnormalities in conjunction with clinical presentation, cognitive profile, and genomics to predict risk and aid in stratification to guide early interventions.

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Authors: Satterthwaite, T. D., Wolf, D. H., Calkins, M. E., Vandekar, S. N., Erus, G., Ruparel, K., Roalf, D. R., Linn, K. A., Elliott, M. A., Moore, T. M., Hakonarson, H., Shinohara, R. T., Davatzikos, C., Gur, R. C., & Gur, R. E.
Affiliations: University of Pennsylvania (US)
Department of Radiology, University of Pennsylvania, Philadelphia
Children's Hospital of Philadelphia (US)
Corresponding author: Satterthwaite, Theodore D.
ORCID: Satterthwaite, Theodore D.
Wolf, Daniel H.
Calkins, Monica E.
Vandekar, Simon N.
Ruparel, Kosha
Roalf, David R.
Linn, Kristin A.
Elliott, Mark A.
Moore, Tyler M.
Hakonarson, Hakon
Shinohara, Russell T.
Davatzikos, Christos
Gur, Ruben C.
Gur, Raquel E.
Venue: JAMA Psychiatry
Publisher: American Medical Association (AMA)
Published: 2016-05-01
Volume: 73
Issue: 5
Pages: 515
ISSN: 2168-622X (ISSN-L)
DOI: 10.1001/jamapsychiatry.2015.3463
PMC: PMC5048443
OpenAlex: W2301077564
Cited by: 132
References: 120
Citations by year: 2026: 7 · 2025: 12 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 7 · 2020: 15 · 2019: 17 · 2018: 17 · 2017: 20 · 2016: 6
FWCI: 17.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: JAMA Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: University of Pennsylvania (R01NS085211)
National Institutes of Health (5r01mh107235-03, 5p50mh064045-10, MH-089983, MH089924)
National Institute of Mental Health (RC2MH089983, P50 MH-064045, P50MH096891, R01-MH-107235, MH089983, K23MH098130, R01MH101111, K01MH102609, MH089924, RC2MH089924, R01MH107703, K08MH079364, T32MH065218)
National Human Genome Research Institute (U01HG008684)
National Institute of Neurological Disorders and Stroke (R01NS085211)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD086984)
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 › Functional Brain Connectivity Studies
Keywords: psychosis spectrum symptoms, youth, structural brain abnormalities, gray matter volume, white matter volume, medial temporal lobe, brain development, symptom severity, Philadelphia Neurodevelopmental Cohort, schizophrenia risk, neuroimaging
MeSH terms: Adolescent, Brain, Child, Female, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Psychotic Disorders, Reference Values, Cohort Studies, Young Adult

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Structural Brain Abnormalities in Youth With Psychosis Spectrum Symptoms

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