Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities.
BACKGROUND
Neuroanatomic abnormalities in schizophrenia may underlie behavioral manifestations. Characterization of such abnormalities is required for interpreting functional data. Frontotemporal abnormalities have been documented by using predetermined region-of-interest approaches, but deformation-based morphometry permits examination of the entire brain.


OBJECTIVE
To perform whole-brain analyses of structural differences between patients with schizophrenia and controls, to examine sex and medication effects, and to apply a high-dimensional nonlinear pattern classification technique to quantify the degree of separation between patients and controls, thereby testing the potential of this new technique as an aid to diagnostic procedures.


METHODS
Whole-brain morphologic analysis using high-dimensional shape transformations.


METHODS
Schizophrenia Research Center, University of Pennsylvania Medical Center.


METHODS
Neuroleptic-naïve and previously treated patients with DSM-IV schizophrenia (n = 69) and sociodemographically matched controls (n = 79).


METHODS
Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the brain.


RESULTS
Magnetic resonance images showed reduced gray matter and increased ventricular cerebrospinal fluid volumes in patients with schizophrenia in the whole brain and in specific foci: the hippocampus and adjacent white matter, the cingulate and orbitofrontal cortex, the frontotemporal and parietotemporal areas, and the occipital areas near the lingual gyrus. The classifier had a mean classification accuracy of 81.1% for men and women combined (82% for women and 85% for men, when each group was treated separately), determined via cross-validation.


CONCLUSIONS
This study confirms previous findings of reduced frontotemporal volumes and suggests new hypotheses, especially involving occipital association and speech production areas. It also suggests finer localization of volume reduction in the hippocampus and other limbic structures and in the frontal lobe. Pattern classification showed high sensitivity and specificity for the diagnosis of schizophrenia, suggesting the potential utility of magnetic resonance imaging as a diagnostic aid.
Davatzikos
Christos
C
Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania Medical Center, 3600 Market Street, Philadelphia, PA 19104, USA. christos@rad.upenn.edu
Shen
Dinggang
D
Gur
Ruben C
RC
Wu
Xiaoying
X
Liu
Dengfeng
D
Fan
Yong
Y
Hughett
Paul
P
Turetsky
Bruce I
BI
Gur
Raquel E
RE
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002555:Cerebrospinal Fluid / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D009778:Occipital Lobe / Q000473:pathology; D009929:Organ Size; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D012565:Schizophrenic Psychology; D012737:Sex Factors; D013060:Speech / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology
D014150:Antipsychotic Agents