LAUSR

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 to 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.