title: Frequency-Specific Neural Signatures of Spontaneous Low-Frequency Resting State Fluctuations in Psychosis: Evidence From Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Consortium.
abstract: BACKGROUND
  We quantified frequency-specific, absolute, and fractional amplitude of low-frequency fluctuations (ALFF/fALFF) across the schizophrenia (SZ)-psychotic bipolar disorder (PBP) psychosis spectrum using resting functional magnetic resonance imaging data from the large BSNIP family study.
  
  
  METHODS
  We assessed 242 healthy controls (HC), 547 probands (180 PBP, 220 SZ, and 147 schizoaffective disorder-SAD), and 410 of their first-degree relatives (134 PBPR, 150SZR, and 126 SADR). Following standard preprocessing in statistical parametric mapping (SPM8), we computed absolute and fractional power (ALFF/fALFF) in 2 low-frequency bands: slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz). We evaluated voxelwise post hoc differences across traditional Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic categories.
  
  
  RESULTS
  Across ALFF/fALFF, in contrast to HC, BP/SAD showed hypoactivation in frontal/anterior brain regions in the slow-5 band and hypoactivation in posterior brain regions in the slow-4 band. SZ showed consistent hypoactivation in precuneus/cuneus and posterior cingulate across both bands and indices. Increased ALFF/fALFF was noted predominantly in deep subcortical and temporal structures across probands in both bands and indices. Across probands, spatial ALFF/fALFF differences in SAD resembled PBP more than SZ. None of these ALFF/fALFF differences were detected in relatives.
  
  
  CONCLUSIONS
  Results suggest ALFF/fALFF is a putative biomarker rather than a familial endophenotype. Overall sensitivity to discriminate proband brain alteration was stronger for fALFF than ALFF. Patterns of differences noted in SAD were more similar to those observed in PBP. Differential effects were noted across the 2 frequency bands, more prominently for BP/SAD compared with SZ, suggesting frequency-sensitive physiologic mechanisms for the former.
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, Hartford, CT; shashwath.meda@hhchealth.org.
authors.forename: Shashwath A
authors.initials: SA
authors.lastname: Meda
authors.affiliation: Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, China;
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX;
authors.forename: Elena I
authors.initials: EI
authors.lastname: Ivleva
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX;
authors.forename: Gaurav
authors.initials: G
authors.lastname: Poudyal
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX;
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX;
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.affiliation: Department of Psychology, University of Georgia, Athens, GA;
authors.forename: Brett A
authors.initials: BA
authors.lastname: Clementz
authors.affiliation: Department of Psychiatry, Johns Hopkins University, Baltimore, MD;
authors.forename: David J
authors.initials: DJ
authors.lastname: Schretlen
authors.forename: Vincent D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China;
authors.forename: Su
authors.initials: S
authors.lastname: Lui
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Eswar
authors.initials: E
authors.lastname: Damaraju
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, Hartford, CT; Department of Psychiatry, Yale University, New Haven, CT; Department of Neurobiology, Yale University, New Haven, CT.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D058256:Brain Waves / Q000502:physiology*; D005190:Family; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011618:Psychotic Disorders / Q000503:physiopathology*; D012559:Schizophrenia / Q000503:physiopathology*
keywords: ALFF; bipolar; fALFF; high risk; relatives; schizoaffective