title: Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy.
abstract: Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features.
authors.affiliation: Department of Computer Science and Artificial Intelligence, University of Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Arnedo
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mamah
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Baranger
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Harms
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Department of Psychology and Department of Anatomy & Neurobiology Washington University, St. Louis, MO, USA.
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Barch
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Dragan M
authors.initials: DM
authors.lastname: Svrakic
authors.affiliation: Roskamp Laboratory of Brain Development, Modulation and Repair, Department of Psychiatry and Behavioral Neurosciences (GAE), University of South Florida, Tampa, FL, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: de Erausquin
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Department of Genetics (CRC), Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: C Robert
authors.initials: CR
authors.lastname: Cloninger
authors.affiliation: Department of Computer Science and Artificial Intelligence, University of Granada, Spain; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: zwiri@psychiatry.wustl.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Zwir
mesh_terms: D000328:Adult; D016880:Anisotropy; D016000:Cluster Analysis; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D066127:White Matter / Q000473:pathology*
keywords: Biclusters; Conceptual clustering; Consensus clustering; Fractional anisotropy; Fuzzy clustering; Generalized factorization; Model-based clustering; Non-negative Matrix Factorization; Positive and negative symptoms; Possibilistic clustering; Relational clustering; Schizophrenias; White matter