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Neuropsychological Testing and Structural Magnetic Resonance Imaging as Diagnostic Biomarkers Early in the Course of Schizophrenia and Related Psychoses

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Abstract

Making an accurate diagnosis of schizophrenia and related psychoses early in the course of the disease is important for initiating treatment and counseling patients and families. In this study, we developed classification models for early disease diagnosis using structural MRI (sMRI) and neuropsychological (NP) testing. We used sMRI measurements and NP test results from 28 patients with recent-onset schizophrenia and 47 healthy subjects, drawn from the larger sample of the Mind Clinical Imaging Consortium. We developed diagnostic models based on Linear Discriminant Analysis (LDA) following two approaches; namely, (a) stepwise (STP) LDA on the original measurements, and (b) LDA on variables created through Principal Component Analysis (PCA) and selected using the Humphrey-Ilgen parallel analysis. Error estimation of the modeling algorithms was evaluated by leave-one-out external cross-validation. These analyses were performed on sMRI and NP variables separately and in combination. The following classification accuracy was obtained for different variables and modeling algorithms. sMRI only: (a) STP-LDA: 64.3% sensitivity and 76.6% specificity, (b) PCA-LDA: 67.9% sensitivity and 72.3% specificity. NP only: (a) STP-LDA: 71.4% sensitivity and 80.9% specificity, (b) PCA-LDA: 78.5% sensitivity and 91.5% specificity. Combined sMRI-NP: (a) STP-LDA: 64.3% sensitivity and 83.0% specificity, (b) PCA-LDA: 89.3% sensitivity and 93.6% specificity. (i) Maximal diagnostic accuracy was achieved by combining sMRI and NP variables. (ii) NP variables were more informative than sMRI, indicating that cognitive deficits can be detected earlier than volumetric structural abnormalities. (iii) PCA-LDA yielded more accurate classification than STP-LDA. As these sMRI and NP tests are widely available, they can increase accuracy of early intervention strategies and possibly be used in evaluating treatment response.

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Acknowledgments

Supported by the United States Department of Energy under Award Number DE-FG02-99ER62764 to The Mind Research Network (formerly The Mental Illness and Neuroscience Discovery [MIND] Institute), the Department of Veterans Affairs, the American Legion Brain Sciences Chair, and the Stanley Medical Research Institute.

The authors thank Dr. Christopher Bingham for advice on the PCA, and Mary A. Jacintha and Kathleen E. Kelly for help in study coordination.

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Authors and Affiliations

  1. Brain Sciences Center (11B), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN, 55417, USA

    Elissaios Karageorgiou, Scott R. Sponheim & Apostolos P. Georgopoulos

  2. Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

    Elissaios Karageorgiou & Apostolos P. Georgopoulos

  3. Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA

    Elissaios Karageorgiou & Apostolos P. Georgopoulos

  4. Center for Cognitive Sciences, University of Minnesota Medical School, Minneapolis, MN, USA

    Elissaios Karageorgiou & Apostolos P. Georgopoulos

  5. Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

    S. Charles Schulz, Scott R. Sponheim & Apostolos P. Georgopoulos

  6. Mind Research Network, Albuquerque, NM, USA

    S. Charles Schulz, Vince D. Calhoun & H. Jeremy Bockholt

  7. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

    Randy L. Gollub

  8. Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa, IA, USA

    Nancy C. Andreasen & Beng-Choon Ho

  9. Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA

    John Lauriello

  10. Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA

    Vince D. Calhoun

  11. Mental Health Patient Service Line, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN, 55417, USA

    Scott R. Sponheim

  12. Department of Psychology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Scott R. Sponheim

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  1. Elissaios Karageorgiou
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  2. S. Charles Schulz
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  3. Randy L. Gollub
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  4. Nancy C. Andreasen
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  5. Beng-Choon Ho
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  6. John Lauriello
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  7. Vince D. Calhoun
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  8. H. Jeremy Bockholt
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  9. Scott R. Sponheim
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  10. Apostolos P. Georgopoulos
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Correspondence to Apostolos P. Georgopoulos.

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Karageorgiou, E., Schulz, S.C., Gollub, R.L. et al. Neuropsychological Testing and Structural Magnetic Resonance Imaging as Diagnostic Biomarkers Early in the Course of Schizophrenia and Related Psychoses. Neuroinform 9, 321–333 (2011). https://doi.org/10.1007/s12021-010-9094-6

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  • DOI: https://doi.org/10.1007/s12021-010-9094-6

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