title: Joint Coupling of Awake EEG Frequency Activity and MRI Gray Matter Volumes in the Psychosis Dimension: A BSNIP Study.
abstract: BACKGROUND
  Many studies have examined either electroencephalogram (EEG) frequency activity or gray matter volumes (GMV) in various psychoses [including schizophrenia (SZ), schizoaffective (SZA), and psychotic bipolar disorder (PBP)]. Prior work demonstrated similar EEG and gray matter abnormalities in both SZ and PBP. Integrating EEG and GMV and jointly analyzing the combined data fully elucidates the linkage between the two and may provide better biomarker- or endophenotype-specificity for a particular illness. Joint exploratory investigations of EEG and GMV are scarce in the literature and the relationship between the two in psychosis is even less explored. We investigated a joint multivariate model to test whether the linear relationship or linkage between awake EEG (AEEG) frequency activity and GMV is abnormal across the psychosis dimension and if such effects are also present in first-degree relatives.
  
  
  METHODS
  We assessed 607 subjects comprising 264 probands [105 SZ, 72 SZA, and 87 PBP], 233 of their first degree relatives [82 SZ relatives (SZR), 71 SZA relatives (SZAR), and 80 PBP relatives (PBPR)], and 110 healthy comparison subjects (HC). All subjects underwent structural MRI (sMRI) and EEG scans. Frequency activity and voxel-based morphometric GMV were derived from EEG and sMRI data, respectively. Seven AEEG frequency and gray matter components were extracted using Joint independent component analysis (jICA). The loading coefficients (LC) were examined for group differences using analysis of covariance. Further, the LCs were correlated with psychopathology scores to identify relationship with clinical symptoms.
  
  
  RESULTS
  Joint ICA revealed a single component differentiating SZ from HC (p < 0.006), comprising increased posterior alpha activity associated with decreased volume in inferior parietal lobe, supramarginal, parahippocampal gyrus, middle frontal, inferior temporal gyri, and increased volume of uncus and culmen. No components were aberrant in either PBP or SZA or any relative group. No significant association was identified with clinical symptom measures.
  
  
  CONCLUSIONS
  Our data suggest that a joint EEG and GMV model yielded a biomarker specific to SZ, not abnormal in PBP or SZA. Alpha activity was related to both increased and decreased volume in different cortical structures. Additionally, the joint model failed to identify endophenotypes across psychotic disorders.
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living , Hartford, CT , USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Soh
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living , Hartford, CT , USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Narayanan
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living , Hartford, CT , USA.
authors.forename: Sabin
authors.initials: S
authors.lastname: Khadka
authors.affiliation: Department of Electrical and Computer Engineering, University of New Mexico , Albuquerque, NM , USA ; The Mind Research Network , Albuquerque, NM , USA ; Department of Psychiatry, Yale University School of Medicine , New Haven, CT , USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, 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: Olin Neuropsychiatry Research Center, Institute of Living , Hartford, CT , USA ; Department of Psychiatry, Yale University School of Medicine , New Haven, CT , USA ; Department of Neurobiology, Yale University School of Medicine , New Haven, CT , USA.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
keywords: EEG; biomarkers; endophenotypes; gray matter; joint independent component analysis; psychotic bipolar; schizoaffective; schizophrenia