title: Large-Scale Fusion of Gray Matter and Resting-State Functional MRI Reveals Common and Distinct Biological Markers across the Psychosis Spectrum in the B-SNIP Cohort.
abstract: To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses [schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar I disorder with psychosis (BP)] and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives, and 242 healthy controls (1). All subjects underwent structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) scanning. Joint-independent component analysis (jICA) was used to fuse sMRI gray matter and rs-fMRI amplitude of low-frequency fluctuations data to identify the relationship between the two modalities. jICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal-striatal-thalamic-cerebellar network and structural abnormalities in the default mode network was found to be common across psychotic diagnoses and correlated with cognitive function, social function, and schizo-bipolar scale scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality). Using a multivariate-fused approach involving two widely used imaging markers, we demonstrate both shared and distinct biological traits across the psychosis spectrum. Furthermore, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes.
authors.affiliation: Mental Health Institute of the Second Xiangya Hospital, Central South University , Changsha , China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital , Hartford, CT , USA.
authors.forename: Shashwath A
authors.initials: SA
authors.lastname: Meda
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center , Dallas, TX , USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center , Dallas, TX , USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.affiliation: Department of Psychology, University of Georgia , Athens, GA , USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Clementz
authors.affiliation: Department of Psychiatry, Johns Hopkins University , Baltimore, MD , USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schretlen
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA; The Mind Research Network, Albuquerque, NM, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Radiology, Huaxi MR Research Center, West China Hospital of Sichuan University , Chengdu , China.
authors.forename: Su
authors.initials: S
authors.lastname: Lui
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, Hartford, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
keywords: bipolar; joint-independent component analysis; multimodal neuroimaging; relatives; schizoaffective; schizophrenia