title: Medial temporal lobe default mode functioning and hippocampal structure as vulnerability indicators for schizophrenia: a MRI study of non-psychotic adolescent first-degree relatives.
abstract: BACKGROUND
  Clues to the etiology and pathophysiology of schizophrenia can be examined in their first-degree relatives because they are genetically related to an ill family member, and have few confounds like medications. Brain abnormalities observed in young relatives are neurobiological indicators of vulnerability to illness. We examined the hypothesis that the hippocampus and parahippocampus are structurally abnormal and are related to default mode network (DMN) function and cognitive abnormalities in relatives of probands.
  
  
  METHODS
  Subjects were 27 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 48 normal controls, ages 13 to 28, undergoing high-resolution magnetic resonance imaging (MRI) at 1.5 T. After structural scan acquisition a subset of subjects performed 2-back working memory (WM) and 0-back tasks during functional MRI (fMRI) alternating with rest. fMRI data were analyzed using SPM-8. Volumes of total cerebrum, hippocampus, and parahippocampal gyrus were measured using semi-automated morphometry.
  
  
  RESULTS
  Compared to controls, relatives had significantly smaller left hippocampi, without volumetric reduction in the parahippocampus. Relatives showed significantly less suppression of DMN activity in the left parahippocampal gyrus. Left hippocampal and posterior parahippocampal volumes were inversely and significantly associated with DMN processing (smaller volumes, less suppression) in relatives. Task suppression in parahippocampal gyrus significantly correlated with WM performance within the relatives.
  
  
  CONCLUSIONS
  Results support the hypothesis that the vulnerability to schizophrenia includes smaller hippocampi and DMN suppression deficits, and these are associated with poorer WM. Findings suggest a primary structural, neurodevelopmental, medial temporal lobe abnormality associated with altered DMN function independent of psychosis.
authors.affiliation: Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA 02115, United States; Harvard Medical School, Department of Psychiatry at Massachusetts General Hospital, Boston, MA 02114, United States; Martinos Center for Biomedical Imaging, Massachusetts Institute of Technology, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, United States; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA 02115, United States. Electronic address: lseidman@bidmc.harvard.edu.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Harvard Medical School Department of Psychiatry at McLean Hospital, Belmont, MA 02478, United States.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Rosso
authors.affiliation: Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA 02115, United States; Harvard Medical School, Department of Psychiatry at Massachusetts General Hospital, Boston, MA 02114, United States; Martinos Center for Biomedical Imaging, Massachusetts Institute of Technology, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, United States; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA 02115, United States.
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Thermenos
authors.affiliation: Harvard Medical School, Department of Psychiatry at Massachusetts General Hospital, Boston, MA 02114, United States; Martinos Center for Biomedical Imaging, Massachusetts Institute of Technology, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, United States; Harvard Medical School Departments of Neurology and Radiology Services, Center for Morphometric Analysis, Massachusetts General Hospital, Boston, MA 02129, United States.
authors.forename: Nikos
authors.initials: N
authors.lastname: Makris
authors.affiliation: Harvard Medical School, Department of Psychiatry at Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Juelich
authors.affiliation: Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Harvard-MIT Division of Health Sciences and Technology, Poitras Center for Affective Disorders Research, Cambridge, MA 02139, United States.
authors.forename: John D E
authors.initials: JD
authors.lastname: Gabrieli
authors.affiliation: Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA 02115, United States; SUNY Genetics Research Program, Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA 02115, United States; University of California, San Diego, Department of Psychiatry, Institute of Behavior Genomics, La Jolla, CA 92093, United States.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Harvard-MIT Division of Health Sciences and Technology, Poitras Center for Affective Disorders Research, Cambridge, MA 02139, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology*; D020534:Parahippocampal Gyrus / Q000473:pathology* / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D013702:Temporal Lobe / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
keywords: Default mode; Genetics; Hippocampus; MRI; Parahippocampus; Relatives; Schizophrenia