Elsevier

Biological Psychiatry

Volume 77, Issue 6, 15 March 2015, Pages 581-588
Biological Psychiatry

Archival Report
In Vivo Hippocampal Subfield Volumes in Schizophrenia and Bipolar Disorder

https://doi.org/10.1016/j.biopsych.2014.06.020Get rights and content

Abstract

Background

Hippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects.

Methods

Clinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum [n = 210; mean age, 32.0 ± 9.3 (SD) years; 59% male], patients with bipolar spectrum [n = 192; mean age, 35.5 ± 11.5 years; 40% male] and healthy control subjects [n = 300; mean age, 35.3 ± 9.9 years; 53% male]). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory [California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated Scale of Intelligence]) were performed.

Results

Patient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 × 10−6; right, p = 2.3 × 10−6), CA4/dentate gyrus (left, p = 1.4 × 10−5; right, p = 2.3 × 10−6), subiculum (left, p = 3.7 × 10−6; right, p = 2.8 × 10−8), and right CA1 (p = .006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 × 10−5; right, p = 1.6 × 10−7). Patients with schizophrenia had smaller subiculum (left, p = .035; right, p = .031) and right presubiculum (p = .002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia.

Conclusions

Hippocampal subfield volume reductions are found in patients with schizophrenia and bipolar disorder. The magnitude of reduction is greater in patients with schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum.

Section snippets

Subjects

The subject sample (N = 702) consisted of patients with a DSM-IV diagnosis within the schizophrenia spectrum (n = 210; schizophrenia [DSM-IV 295.1, 295.3, 295.6, 295.9; n = 161], schizophreniform disorder [DSM-IV 295.4; n = 21], or schizoaffective disorder [DSM-IV 295.7; n = 28]), patients with a DSM-IV diagnosis within the bipolar spectrum (n = 192; bipolar I disorder [DSM-IV 296.0-7; n = 117], bipolar II disorder [DSM-IV 296.89; n = 66], or bipolar disorder not otherwise specified [DSM-IV

Demographic and Clinical Variables

Demographic and clinical variables are presented in Table 1.

Hippocampal Subfield Volume Differences Between Diagnostic Groups

Volume differences between groups (Table 2) were found in hippocampal subfields CA2/3, CA4/DG, presubiculum, and subiculum bilaterally and right CA1 when age and ICV were accounted for; patients with schizophrenia or bipolar disorder had smaller volumes than healthy control subjects for all subfields except the presubiculum, where only patients with schizophrenia had smaller volumes (Table 3). Both patient groups showed smaller right

Discussion

The main findings in this study were smaller in vivo volumes of the hippocampal subfields CA2/3, CA4/DG, subiculum, and right CA1 in patients with schizophrenia and patients with bipolar disorder compared with healthy control subjects, with distinctly smaller subiculum and presubiculum volumes in patients with schizophrenia compared with patients with bipolar disorder.

Subiculum and presubiculum constitute the outflow parts of the hippocampal neuronal circuitry (8) and receive the major output

Acknowledgment and disclosures

This work was supported by the Research Council of Norway Grant Nos. 190311/V50, 167153/V50, and 204966/F20; the South Eastern Norway Regional Health Authority Grant Nos. 2008011, 2009037, and 2011096; and the K.G. Jebsen Foundation. The funding organizations had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the article; or in the decision to submit the article for publication.

AMD is a founder and holds equity in CorTechs Labs and

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