title: Altered hippocampal-parahippocampal function during stimulus encoding: a potential indicator of genetic liability for schizophrenia.
abstract: OBJECTIVE
  Declarative memory-the ability to learn, store, and retrieve information-has been consistently reported to be altered in schizophrenia, and hippocampal-parahippocampal dysfunction has been implicated in this deficit. To elucidate the possible role of genetic risk factors in such findings, it is necessary to study healthy relatives of patients with schizophrenia who carry risk-associated genes but not the confounding factors related to the disorder.
  
  
  OBJECTIVE
  To investigate whether altered brain responses, particularly in the hippocampus and parahippocampus, during the encoding phase of a simple declarative memory task are also observed in unaffected siblings who are at increased genetic risk for schizophrenia.
  
  
  METHODS
  Functional magnetic resonance imaging was used with a simple visual declarative memory paradigm to test for differences in neural activation across normal control participants, patients with schizophrenia, and their healthy siblings. This study was conducted at a research center and included a total of 308 participants (181 normal control participants, 65 healthy siblings, and 62 patients with schizophrenia); all participants were white of European ancestry.
  
  
  METHODS
  All participants completed a declarative memory task involving incidental encoding of neutral visual scenes interleaved with crosshair fixation while undergoing functional magnetic resonance imaging. Differences in hippocampus and parahippocampus activation and coupling across groups and correlations with accuracy were analyzed. Analyses were repeated in pairwise-matched samples.
  
  
  RESULTS
  Both patients with schizophrenia and their healthy siblings showed reduced parahippocampal activation (bilaterally) and hippocampal-parietal (BA 40) coupling during the encoding of novel stimuli when compared with normal control participants. There was a significant positive correlation between parahippocampal activation during encoding and the visual-memory score.
  
  
  CONCLUSIONS
  These results suggest that altered hippocampal-parahippocampal function during encoding is an intermediate biologic phenotype related to increased genetic risk for schizophrenia. Therefore, measuring hippocampal-parahippocampal function with neuroimaging represents a potentially useful approach to understanding genetic mechanisms that confer risk for schizophrenia.
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rasetti
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland2Lieber Institute for Brain Development, Johns Hopkins Medical Camp.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Mattay
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland2Lieber Institute for Brain Development, Johns Hopkins Medical Camp.
authors.forename: Michael G
authors.initials: MG
authors.lastname: White
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland3Brain Center for Motor and Social Cognition, Istituto Italiano di.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sambataro
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Podell
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
authors.forename: Brad
authors.initials: B
authors.lastname: Zoltick
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland2Lieber Institute for Brain Development, Johns Hopkins Medical Camp.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Berman
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Callicott
authors.affiliation: Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland2Lieber Institute for Brain Development, Johns Hopkins Medical Camp.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology*; D059906:Neuroimaging / Q000295:instrumentation / Q000379:methods*; D020534:Parahippocampal Gyrus / Q000503:physiopathology*; D010296:Parietal Lobe / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D035781:Siblings