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Original Investigation |

Medial Temporal Lobe Structures and Hippocampal Subfields in Psychotic Disorders:  Findings From the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study

Ian Mathew, BA1; Tova M. Gardin, BS1; Neeraj Tandon, BS1,2; Shaun Eack, PhD3,4; Alan N. Francis, MPhil5; Larry J. Seidman, PhD1,5; Brett Clementz, PhD6,7; Godfrey D. Pearlson, MD8,9; John A. Sweeney, PhD10; Carol A. Tamminga, MD10; Matcheri S. Keshavan, MD1
[+] Author Affiliations
1Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
2Baylor College of Medicine, Houston, Texas
3School of Social Work, University of Pittsburgh, Pittsburgh, Pennsylvania
4Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
5Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School Athinoula A. Martinos Center for Biomedical Imaging, Boston
6Department of Psychology, BioImaging Research Center, University of Georgia, Athens
7Department of Neuroscience, BioImaging Research Center, University of Georgia, Athens
8Olin Neuropsychiatry Research Center, Institute of Living, Hartford, Connecticut
9Yale University School of Medicine, New Haven, Connecticut
10University of Texas Southwestern Medical Center, Dallas
JAMA Psychiatry. 2014;71(7):769-777. doi:10.1001/jamapsychiatry.2014.453.
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Importance  Structural alterations in the hippocampus and other medial temporal lobe regions have been observed in schizophrenia. How these alterations and hippocampal subfields might differ across the psychosis spectrum remains unclear.

Objectives  To characterize medial temporal lobe structures, including hippocampal subfields, using magnetic resonance imaging and to examine their relation to psychosis and cognitive function across the psychosis spectrum.

Design, Setting, and Participants  Case-control, cross-sectional neuroimaging study in a large series of probands with psychotic disorders and healthy volunteers as part of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Patients with psychotic disorders (schizophrenia, n = 219; schizoaffective disorder, n = 142; and psychotic bipolar disorder, n = 188) and healthy controls (n = 337) were recruited across ambulatory clinics at university health centers in the B-SNIP consortium.

Main Outcomes and Measures  Medial temporal lobe and hippocampal subfields were quantified with an automated parcellation approach using FreeSurfer software. Memory and other cognitive parameters were assessed using standardized neuropsychological tests.

Results  Hippocampal volume reductions were seen in all 3 diagnostic groups when compared with healthy controls; alterations in the entorhinal cortex and parahippocampal regions were limited to schizophrenia and schizoaffective disorders (P < .001). Smaller volumes across the hippocampal subfields were seen in all 3 psychotic disorders, with the most prominent differences being in cornu ammonis 2/3 (P < .001). Hippocampal volumes were positively correlated with psychosis severity, declarative memory, and overall cognitive performance (P < .05).

Conclusions and Relevance  Alterations in the hippocampus were evident across psychotic disorders. Hippocampal subfields that participate in memory-related processes supporting pattern separation and pattern completion might be abnormal and may underlie the pathophysiology of psychosis.

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Figure 1.
Hippocampal Subfield Segmentation

A, FreeSurfer segmentation and location of different subfields within the hippocampus. CA indicates cornu ammonis; DG, dentate gyrus. Effect sizes per group according to the Cohen d color scale are shown for healthy controls (HCs) vs probands (B), HCs vs patients with schizophrenia (SZ) (C), HCs vs patients with schizoaffective disorder (SZA) (D), and HCs vs patients with psychotic bipolar disorder (BPP) (E).

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Figure 2.
Relationship of Left Hippocampal Volume With Brief Assessment of Cognition in Schizophrenia (BACS) Composite and List-Learning Scores

Scatterplot of individual-specific data for all participants and diagnostic group correlations. A, Correlation between BACS composite scores (z scale) and left hippocampal volume, with healthy controls (HCs) separate from probands. B, Correlation between list-learning scores (z scale) and left hippocampal volume, with HCs separate from probands. BPP indicates psychotic bipolar disorder; SZ, schizophrenia; and SZA, schizoaffective disorder.

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