title: Hippocampal dysfunction during declarative memory encoding in schizophrenia and effects of genetic liability.
abstract: Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological relatives of patients. However, the neural correlates of successful and unsuccessful encoding, mediated by the medial temporal lobe (MTL) memory system, and the influence of disease-related genetic liability remain under explored. This study employed an event-related functional MRI paradigm to compare activations for successfully and unsuccessfully encoded associative face-name stimuli between 26 schizophrenia patients (mean age: 33, 19m/7f), 30 controls (mean age: 29, 24m/6f), and 14 unaffected relatives of patients (mean age: 40, 5m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporo-parietal cortical association areas when contrasting successfully encoded events to fixation. Follow-up hippocampal regions-of-interest analysis revealed schizophrenia-related hyper-activations in the right anterior hippocampus during successful encoding; contrasting successful versus unsuccessful events produced schizophrenia-related hypo-activations in the left anterior hippocampus. Similar hippocampal hypo-activations were observed in unaffected relatives during successful versus unsuccessful encoding. Post hoc analyses of hippocampal volume showed reductions in patients, but not in unaffected relatives compared to controls. Findings suggest that DM encoding deficits are attributable to both disease-specific and genetic liability factors that impact different components of the MTL memory system. Hyper-activations in temporo-occipital and parietal regions observed only in patients suggest the influence of disease-related factors. Regional hyper- and hypo-activations attributable to successful encoding occurring in both patients and unaffected relatives suggest the influence of schizophrenia-related genetic liability factors.
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Pirnia
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Woods
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA; Department of Neurological Surgery, University of California, San Francisco, USA.
authors.forename: Liberty S
authors.initials: LS
authors.lastname: Hamilton
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lyden
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
authors.forename: Shantanu H
authors.initials: SH
authors.lastname: Joshi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Geffen School of Medicine, University of California, Los Angeles, USA; Department of Psychology, University of California, Los Angeles, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Asarnow
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Geffen School of Medicine, University of California, Los Angeles, USA; Department of Psychology, University of California, Los Angeles, USA.
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, Geffen School of Medicine, and Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA. Electronic address: narr@ucla.edu.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
mesh_terms: D000328:Adult; D005190:Family; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D009929:Organ Size; D010296:Parietal Lobe / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000503:physiopathology
keywords: Associative memory; Episodic memory; Functional imaging; Hippocampus; Medial temporal lobe; fMRI