Presence, severity, and functional associations of incomplete hippocampal inversion in 22q11.2 deletion syndrome.

Abstract

Background: The hippocampus is smaller and functionally disrupted in individuals with 22q11.2 deletion syndrome (22q11DS), though the cause remains unclear. During gestational weeks 20-30 an inversion in the dentate gyrus and cornu ammonis occurs. This process can go awry resulting in incomplete hippocampal inversion (IHI). In the general population, IHI is more common in the left hemisphere than the right; yet its prevalence, severity, and functional impact in 22q11DS remain unexplored. Investigating IHI in 22q11DS could uncover morphological hippocampal abnormalities linked to neuropsychiatric and neurocognitive symptoms.

Methods: Using 3T structural MRI data, the presence and severity of IHI were assessed in 22q11DS (n=108) and healthy comparison (HC; n=633) individuals. Total and subregional hippocampal volume, psychopathology, and hippocampal-based memory were evaluated.

Results: IHI prevalence was significantly higher in 22q11DS compared to HC in both the left (63% vs. 30%, p<0.001) and right hemispheres (29% vs. 8%, p<0.001). IHI severity was also greater in 22q11DS (p<0.001) bilaterally. IHI influenced hippocampal volume differences, with left IHI primarily affecting the head (p<0.01) and tail (p<0.001) and right IHI affecting only the tail (p<0.001). In exploratory analyses within 22q11DS, left IHI presence was linked to poorer face memory (p<0.05) but not psychopathology.

Conclusions: These findings highlight a high prevalence of hippocampal morphological alterations in 22q11DS, which are associated with memory performance. Earlier developmental and longitudinal studies are needed to clarify the role of IHI in 22q11DS sequelae.