title: Hippocampal volume is reduced in schizophrenia and schizoaffective disorder but not in psychotic bipolar I disorder demonstrated by both manual tracing and automated parcellation (FreeSurfer).
abstract: This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007-.02) and SAD (P = .003-.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18-.55). All relative groups had hippocampal volumes not different from controls (P = .12-.97) and higher than those observed in probands (P = .003-.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64-.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51-.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness.
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Sara J M
authors.initials: SJ
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235; elena.ivleva@utsouthwestern.edu.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Ivleva
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Tejas A
authors.initials: TA
authors.lastname: Gopal
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Anil P
authors.initials: AP
authors.lastname: Reddy
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Haekyung
authors.initials: H
authors.lastname: Jeon-Slaughter
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Sacco
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA;
authors.forename: Alan N
authors.initials: AN
authors.lastname: Francis
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA;
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Anup S
authors.initials: AS
authors.lastname: Bidesi
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Bradley
authors.initials: B
authors.lastname: Witte
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Gaurav
authors.initials: G
authors.lastname: Poudyal
authors.affiliation: Department of Psychiatry, Institute of Living/Hartford Hospital, Yale School of Medicine, New Haven, CT;
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
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, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA;
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D016022:Case-Control Studies; D005190:Family; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011618:Psychotic Disorders / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
keywords: FreeSurfer; hippocampus; manual tracing; psychotic bipolar disorder; schizophrenia