Structural brain abnormalities in youth with psychosis spectrum symptoms

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

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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. O. 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.

Original languageEnglish (US)
Pages (from-to)515-524
Number of pages10
JournalJAMA psychiatry
Issue number5
StatePublished - May 2016

ASJC Scopus subject areas

  • Psychiatry and Mental health


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