Altered developmental trajectories of verbal learning skills in 22q11.2DS: associations with hippocampal development and psychosis

Abstract

Background The cognitive profile in 22q11.2 deletion syndrome (22q11.2DS) is often characterized by a discrepancy between nonverbal vs. 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 22q11.2DS vs. HC. Second, we examined hippocampal volume development in 22q11.2DS participants with lower vs. higher verbal learning performance. Third, we explored verbal learning trajectories in 22q11.2DS participants with vs. without positive psychotic symptoms and with vs. 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.

Effects of Gene Dosage and Development on Subcortical Nuclei Volumes in Individuals with 22q11.2 Copy Number Variations

“…Analysis of hippocampal tail volume relationships to IQ suggests that this region may be particularly related to verbal cognition in 22qDel but not 22qDup or TD. This broadly supports the recent finding of hippocampal tail volume relationships with verbal learning scores in 22qDel [27]. Our analysis was specifically motivated by this prior literature; however, this effect would not have remained significant after correction for multiple comparisons in an exploratory analysis of cognition relationships to all subregional volumes.…”

“…Analysis of hippocampal tail volume relationships to IQ suggests that this region may be particularly related to verbal cognition in 22qDel but not 22qDup or TD. This broadly supports the recent finding of hippocampal tail volume relationships with verbal learning scores in 22qDel [27].…”

“…Motivated by literature relating low hippocampal tail volume to verbal learning impairment in 22qDel [27], we assessed verbal and non-verbal IQ [Wechsler Abbreviated Scale of Intelligence (WASI-2) Vocabulary and Matrix subtest scaled scores] for associations with hippocampal tail volume in each group. Given the relationship between 22qDel and psychosis risk [9,26,51], we additionally tested relationships between psychosis risk symptoms and all subcortical volumes in the 22qDel group.…”

“…Longitudinally, there were steeper thalamic volume decreases over time in individuals with 22qDel who experienced auditory hallucinations. In 22qDel, lower hippocampal tail volume has been related to verbal learning impairments [27], and hippocampal volume loss over time in 22qDel has been linked to altered local balance of excitatory and inhibitory neurotransmitter metabolites [28].…”

Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome

“…Verbal memory in 22q11.2DS is differentially characterized in the literature, with some studies suggesting it as a relative strength and others documenting pronounced deficits. While Woodin et al [9] and Lajiness-O'Neill et al [38] indicate that verbal memory is significantly less impacted than visuospatial memory, research by Maeder et al [29] and Latrèche et al [39] depicts a less optimistic picture, finding significant challenges in both immediate and delayed verbal memory. In combination, these deficits in both immediate and delayed verbal memory suggest a pattern of forgetting that may point to an impaired process of memory consolidation [29].…”