title: Callosal Abnormalities Across the Psychosis Dimension: Bipolar Schizophrenia Network on Intermediate Phenotypes.
abstract: The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relatives; and healthy control subjects.
  
  
  
  We present findings from morphometric and neurocognitive analyses of 1381 subjects (SZ probands, n = 224; PBD probands, n = 190; schizoaffective disorder probands, n = 142; unaffected relatives, n = 483 [SZ relatives, n = 195; PBD relatives, n = 175; schizoaffective disorder relatives, n = 113]; control subjects, n = 342). Magnetization prepared rapid acquisition gradient-echo T1 scans across five sites were obtained using 3-tesla magnets. Image processing was done using FreeSurfer Version 5.1. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia scale.
  
  
  
  Anterior and posterior splenial volumes were significantly reduced across the groups. The SZ and PBD probands showed robust and significant reductions, whereas relatives showed significant reductions of intermediate severity. The splenial volumes were positively but differentially correlated with aspects of cognition in the probands and their relatives. Proband groups showed a significant age-related decrease in the volume of the anterior splenium compared with control subjects. Among the psychosis groups, the anterior splenium in probands with PBD showed a stronger correlation with psychotic symptoms, as shown by the Positive and Negative Syndrome Scale. All five subregions showed significantly high familiality.
  
  
  
  The splenial volumes were significantly reduced across the psychosis dimension. However, this volume reduction impacts cognition and clinical manifestation of the illnesses differentially.
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts. Electronic address: afrancis@mclean.harvard.edu.
authors.forename: Alan N
authors.initials: AN
authors.lastname: Francis
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard University, Boston.
authors.forename: Suraj S
authors.initials: SS
authors.lastname: Mothi
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard University, Boston.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Mathew
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard University, Boston.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Department of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, Georgia.
authors.forename: Brett
authors.initials: B
authors.lastname: Clementz
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living, Hartford; Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard University, Boston.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D001284:Atrophy / Q000473:pathology; D001714:Bipolar Disorder / Q000473:pathology* / Q000523:psychology; D016022:Case-Control Studies; D003071:Cognition; D003337:Corpus Callosum / Q000473:pathology*; D058068:Endophenotypes; D005190:Family / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010641:Phenotype; D011618:Psychotic Disorders / Q000473:pathology* / Q000523:psychology; D012559:Schizophrenia / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult
keywords: Bipolar; Corpus callosum; Neuroimaging; Psychosis; Schizoaffective; Schizophrenia