Subfield-specific longitudinal changes of hippocampal volumes in patients with early-stage bipolar disorder

Abstract

Background: The hippocampus is a heterogeneous structure composed of biologically and functionally distinct subfields. Hippocampal aberrations are proposed to play a fundamental role in the etiology of psychotic symptoms. Bipolar disorder (BPD) has substantial overlap in symptomatology and genetic liability with schizophrenia (SZ), and reduced hippocampal volumes, particularly at the chronic illness stages, are documented in both disorders. Studies of hippocampal subfields in the early stage of BPD are limited and cross-sectional findings to date report no reduction in hippocampal volumes. To our knowledge, there have been no longitudinal studies of BPD evaluating hippocampal volumes in the early phase of illness. We investigated the longitudinal changes in hippocampal regions and subfields in BPD mainly and in early stage of psychosis (ESP) patients more broadly and compared them to those in controls (HC).

Methods: Baseline clinical and structural MRI data were acquired from 88 BPD, from a total of 143 ESP patients, and 74 HCs. Of those, 66 participants (23 HC, 43 patients) completed a 12-month follow-up visit. The hippocampus regions and subfields were segmented using Freesurfer automated pipeline.

Results: We found general baseline deficits in hippocampal volumes among BPD and ESP cohorts. Both cohorts displayed significant increases in the anterior hippocampal region and dentate gyrus compared with controls. Additionally, antipsychotic medications were positively correlated with the posterior region at baseline.

Conclusion: These findings highlight brain plasticity in BPD and in ESP patients providing evidence that deviations in hippocampal volumes are adaptive responses to atypical signaling rather than progressive degeneration.

Keywords: bipolar disorder; early-stage psychosis; hippocampus subfield volumes; longitudinal.

FIGURE 1

Hippocampal regions (anterior, posterior) and subfields (CA, DG, Sub) from a single subject. A, anterior; CA, Cornu Ammonis; DG, dentate gyrus; P, posterior; Sub, subiculum.

FIGURE 2

Psychosis patients display no hippocampal volume atrophy over time. Hippocampal volume residuals are calculated after taking the effects of sex, age, and ICV into account, and segmented by region (anterior and posterior) and subfield (cornu ammonis, dentate gyrus, subiculum). Volumes in the anterior region and dentate gyrus increased significantly in (A) BPD and (B) ESP at follow-up (indicated by star sign). Hippocampal volume residuals are stratified by diagnosis group and time point where individual participant data are represented by points; the estimated marginal mean change in segmented hippocampal regions across time points is indicated by the line plot; and the distribution of volumes at each time-point is indicated by density plots. BPD, bipolar disorder with psychosis; ESP, early-stage psychosis; HC, healthy control.