Background: The cognitive profile in 22q11.2 deletion syndrome (22q11.2DS) is often characterized by a discrepancy between nonverbalvs.verbal reasoning skills, in favor of the latter skills. This dissociation has also been observed in memory, with verbal learning skills described as a relative strength. Yet the development of these skills is still to be investigated. We thus aimed to explore verbal learning longitudinally. Furthermore, we explored verbal learning and its respective associations with hippocampal alterations and psychosis, which remain largely unknown despite their high prevalence in 22q11.2DS.

Methods: In total, 332 individuals (173 with 22q11.2DS) aged 5-30 years completed a verbal-paired associates task. Mixed-models regression analyses were conducted to explore developmental trajectories with threefold objectives. First, verbal learning and retention trajectories were compared between 22q11.2DSvs.HC. Second, we examined hippocampal volume development in 22q11.2DS participants with lowervs.higher verbal learning performance. Third, we explored verbal learning trajectories in 22q11.2DS participants withvs.without positive psychotic symptoms and withvs.without a psychotic spectrum disorder (PSD).

Results: Our findings first reveal lower verbal learning performance in 22q11.2DS, with a developmental plateau emerging from adolescence. Second, participants with lower verbal learning scores displayed a reduced left hippocampal tail volume. Third, participants with PSD showed a deterioration of verbal learning performance, independently of verbal reasoning skills.

Conclusion: Our study challenges the current view of preserved verbal learning skills in 22q11.2DS and highlights associations with specific hippocampal alterations. We further identify verbal learning as a novel cognitive marker for psychosis in 22q11.2DS.