Neuropsychological testing and structural magnetic resonance imaging as diagnostic biomarkers early in the course of schizophrenia and related psychoses.
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.
Brain Sciences Center (11B), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA. karag001@umn.edu
Elissaios
E
Karageorgiou
S Charles
SC
Schulz
Randy L
RL
Gollub
Nancy C
NC
Andreasen
Beng-Choon
BC
Ho
John
J
Lauriello
Vince D
VD
Calhoun
H Jeremy
HJ
Bockholt
Scott R
SR
Sponheim
Apostolos P
AP
Georgopoulos
D000328:Adult; D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards; D008297:Male; D008959:Models, Neurological; D009483:Neuropsychological Tests / Q000592:standards*; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000523:psychology; D012559:Schizophrenia / Q000175:diagnosis* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D055815:Young Adult
D015415:Biomarkers
Schizophr Res. 2006 Oct;87(1-3):297-306
16797923
Schizophr Bull. 2010 Mar;36(2):400-9
18682375
Arch Gen Psychiatry. 1990 Jan;47(1):35-44
2294854
J Clin Psychol. 1981 Apr;37(2):347-53
7229070
Schizophr Bull. 2001;27(3):349-77
11596841
Am J Public Health. 2007 Oct;97(10):1756-7
17895405
Neuroimage. 2009 May 15;46(1):177-92
19233293
Synapse. 2008 Aug;62(8):616-27
18509852
J Psychiatr Res. 1994 May-Jun;28(3):239-65
7932285
Arch Gen Psychiatry. 2001 Jan;58(1):33-40
11146756
Neuron. 2002 Jan 31;33(3):341-55
11832223
Biol Psychiatry. 2008 Dec 15;64(12):1060-8
18814865
Psychiatry Res. 1999 Feb 22;90(1):1-15
10320207
Neuroimage. 2006 Apr 1;30(2):436-43
16300968
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6562-6
11983868
Brain. 1999 Apr;122 ( Pt 4):593-624
10219775
Arch Gen Psychiatry. 1992 Aug;49(8):615-23
1637251
Schizophr Bull. 2009 Jan;35(1):82-95
18997157
J Neural Eng. 2007 Dec;4(4):349-55
18057502
Schizophr Res. 2008 Dec;106(2-3):140-7
18818054
Schizophr Res. 2008 Apr;101(1-3):111-23
18272348
Biol Psychiatry. 2007 May 15;61(10):1148-56
17098213
J Psychiatr Res. 2010 May;44(7):421-8
19878956
Philos Trans R Soc Lond B Biol Sci. 1982 Jun 25;298(1089):199-209
6125971
Stat Med. 2005 Dec 30;24(24):3687-96
16320261
Behav Res Methods Instrum Comput. 2000 Aug;32(3):396-402
11029811
Schizophr Res. 2002 Sep 1;57(1):43-9
12165375
Psychol Med. 2003 Jan;33(1):97-110
12537041
Percept Mot Skills. 1993 Jun;76(3 Pt 2):1219-30
8337069
Am J Psychiatry. 1970 Jan;126(7):983-7
5409569
Eur Arch Psychiatry Clin Neurosci. 2004 Dec;254(6):406-14
15538599
Psychiatry Res. 2007 Apr 15;154(3):199-208
17360162
Psychiatry Res. 2008 Jun 30;159(3):281-9
18448171
Schizophr Bull. 2008 Mar;34(2):354-66
18283048
J Psychiatry Neurosci. 1999 Sep;24(4):341-7
10516802
Br J Psychol. 1970 Aug;61(3):303-21
5457503
J Int Bioethique. 2004 Mar;15(1):124-9
15835069