ArticleSchizophrenia research2025
Hippocampal subfield activity in schizophrenia: Effects of the disease course.
Article in Schizophrenia research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Alterations in hippocampal structure and function are established in schizophrenia. However, the specific patterns of hippocampal activity along the schizophrenia course remain unknown. Eighty-five study participants [34 schizophrenia probands (SZ), 32 first-degree relatives (REL), 19 healthy controls (HC)] underwent 3Tesla ultra-high resolution brain MRI (Vascular Space Occupancy); relative cerebral blood volume (rCBV)-an index of regional activity-was estimated across hippocampal subfields: dentate gyrus (DG), CA3, CA1, and subiculum (SUB). To examine effects of the schizophrenia course, SZ were stratified into SZ-Early (≤7 yrs. from psychosis onset), SZ-Mid-Course (8-14 yrs) and SZ-Advanced (≥15 yrs). REL were grouped into those with (RELP) and without (REL-NP) psychosis spectrum disorders. Medication effects were examined by contrasting SZ on- vs. off-antipsychotics. No hippocampal rCBV differences emerged in SZ vs. HC or in SZ-on vs. SZ-off antipsychotic medications. However, among the SZ course groups, SZ-Early showed elevated rCBV in CA3, CA1 and DG compared to SZ-Advanced and HC (p = .004-032). Illness duration-based cross-sectional "trajectories" demonstrated elevated hippocampal rCBV within the initial 7 yrs., followed by an intermediary plateau (8-20 yrs), and a subsequent decline in advanced (20+ yrs) SZ. Among biological relatives of SZ, REL-P vs. HC showed reduced rCBV in SUB, CA1 and DG (p = .021-0.046). Our findings demonstrate differential patterns of hippocampal rCBV along the schizophrenia course. Regional hippocampal activity may serve as a granular biomarker sensitive to the effects of the schizophrenia course and, via future work, inform SZ stage-specific interventions: e.g., reducing hippocampal hyperactivity in early-course SZ vs. enhancing this same circuit's function in advanced stages of SZ.
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