Hippocampal dysfunction during declarative memory encoding in schizophrenia and effects of genetic liability

SCHIZOPHRENIA RESEARCH

卷:161

Article

Pirnia, Tara^1,2  Woods, Roger P.^1,2  Hamilton, Liberty S.^1,2,5  Lyden, Hannah^1,2  Joshi, Shantanu H.^1,2  Asarnow, Robert F.^3,4  Nuechterlein, Keith H.^3,4  Narr, Katherine L.^1,2 

[1] Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA

[4] UCLA, Dept Psychol, Los Angeles, CA 90095 USA

[5] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

关键词: Hippocampus;    fMRI;    Functional imaging;    Episodic memory;    Associative memory;    Medial temporal lobe;   

DOI  :  10.1016/j.schres.2014.11.030

来源: Elsevier

【 摘 要 】

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, 19 m/7f), 30 controls (mean age: 29, 24 m/6f), and 14 unaffected relatives of patients (mean age: 40, 5 m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporoparietal 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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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