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<p>The hippocampus and amygdala form a tightly integrated circuit supporting memory-emotion integration and stress regulation, critically implicated in psychosis development. However, the maturation of the hippocampus-amygdala (HIP-AMY) complex as a functional unit remains poorly understood. 22q11.2 deletion syndrome (22q11DS), with increased risk of schizophrenia, provides a valuable model to study its neurodevelopmental trajectories. A prospective longitudinal cohort of 133 individuals with 22q11DS and 150 healthy controls (HC) underwent neuroimaging and psychiatric assessments approximately every three years. Resting-state fMRI data were analysed using a data-driven clustering approach to identify transient states of dynamic functional connectivity linked to the activation of specific ensembles of HIP-AMY nuclei. State occurrences over age were compared between 22q11DS and HC and between 22q11DS individuals with and without positive psychotic symptoms (PPS+ and PPS−). Seven HIP-AMY states were identified, three showing significant and one trend-level age-by-diagnosis interaction. Importantly, the occurrence of a CA3-centromedial amygdala driven state showing co-activation of limbic and thalamo-striatal salience hubs decreased over age in HC, but remained elevated in 22q11DS. This divergence was reflected within 22q11DS, with PPS− showing a decrease and PPS+ a modest increase. The persistence of this pattern over development may provide a dynamic signature of emergence of psychosis.</p>

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Dynamic reconfiguration of subunits from the hippocampal-amygdala complex indicate patterns of psychosis vulnerability in 22q11.2 deletion syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • Laura Fusi,
  • Farnaz Delavari,
  • Silas Forrer,
  • Corrado Sandini,
  • Dimitri Van De Ville,
  • Stéphan Eliez

摘要

The hippocampus and amygdala form a tightly integrated circuit supporting memory-emotion integration and stress regulation, critically implicated in psychosis development. However, the maturation of the hippocampus-amygdala (HIP-AMY) complex as a functional unit remains poorly understood. 22q11.2 deletion syndrome (22q11DS), with increased risk of schizophrenia, provides a valuable model to study its neurodevelopmental trajectories. A prospective longitudinal cohort of 133 individuals with 22q11DS and 150 healthy controls (HC) underwent neuroimaging and psychiatric assessments approximately every three years. Resting-state fMRI data were analysed using a data-driven clustering approach to identify transient states of dynamic functional connectivity linked to the activation of specific ensembles of HIP-AMY nuclei. State occurrences over age were compared between 22q11DS and HC and between 22q11DS individuals with and without positive psychotic symptoms (PPS+ and PPS−). Seven HIP-AMY states were identified, three showing significant and one trend-level age-by-diagnosis interaction. Importantly, the occurrence of a CA3-centromedial amygdala driven state showing co-activation of limbic and thalamo-striatal salience hubs decreased over age in HC, but remained elevated in 22q11DS. This divergence was reflected within 22q11DS, with PPS− showing a decrease and PPS+ a modest increase. The persistence of this pattern over development may provide a dynamic signature of emergence of psychosis.