Schizophrenia research · 2026
Negative symptom dimensions link cognitive impairment to global and social functioning in 22q11.2 deletion syndrome.
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Parker David A, Chen Marissa, Walker Elaine F, Imes Sidney, Ruban Gabrielle A, Ousley Opal Y, Henshey Brett, Massa Nicholas M, Pearce Bradley, Cubells Joseph F, Duncan Erica
Аннотация
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) confers a 20-30% lifetime risk of schizophrenia, with negative symptoms associated with poorer outcomes and higher psychosis risk. High rates of neurocognitive deficits, autism spectrum traits (ASD), and attention-deficit/hyperactivity disorder (ADHD) may further complicate symptom profiles and functional outcomes. We examined relationships among positive and negative symptom severity, ASD traits, ADHD symptoms, and global functioning in 22q11DS.
METHODS: Individuals with 22q11DS (n = 38) and healthy comparison subjects (n = 34) completed clinical and cognitive assessments. Exploratory factor analysis (EFA) of the 19 items on the Structured Interview for Psychosis-Risk Syndromes (SIPS) derived empirical symptom dimensions. Group differences were evaluated using Mann-Whitney U tests. Mediation analyses examined whether SIPS-derived factors mediated relationships between cognition and three domains: global functioning, ASD traits, and ADHD symptom severity.
RESULTS: EFA identified three symptom dimensions: (1) Positive/Disorganized, (2) Negative-Motivational, and (3) Negative-Expressive. Compared to healthy comparisons, 22q11DS subjects showed elevated scores across all three symptom dimensions, ASD subscales, and ADHD domains (except hyperactivity/restlessness), alongside significant neurocognitive and global functioning impairments. The Negative-Expressive factor was the strongest mediator, showing the largest indirect effects for global functioning and ASD traits. The Negative-Motivational factor was the only dimension to significantly mediate all three outcomes. The Positive/Disorganized factor mediated effects only on global functioning and ASD traits.
CONCLUSION: Negative-expressive symptoms represent a core pathway linking cognitive deficits to functional impairment in 22q11DS, while motivational and positive symptom dimensions contribute differentially across functional domains. Expressive and motivational symptoms may represent candidate targets for future longitudinal and intervention studies in 22q11DS.
METHODS: Individuals with 22q11DS (n = 38) and healthy comparison subjects (n = 34) completed clinical and cognitive assessments. Exploratory factor analysis (EFA) of the 19 items on the Structured Interview for Psychosis-Risk Syndromes (SIPS) derived empirical symptom dimensions. Group differences were evaluated using Mann-Whitney U tests. Mediation analyses examined whether SIPS-derived factors mediated relationships between cognition and three domains: global functioning, ASD traits, and ADHD symptom severity.
RESULTS: EFA identified three symptom dimensions: (1) Positive/Disorganized, (2) Negative-Motivational, and (3) Negative-Expressive. Compared to healthy comparisons, 22q11DS subjects showed elevated scores across all three symptom dimensions, ASD subscales, and ADHD domains (except hyperactivity/restlessness), alongside significant neurocognitive and global functioning impairments. The Negative-Expressive factor was the strongest mediator, showing the largest indirect effects for global functioning and ASD traits. The Negative-Motivational factor was the only dimension to significantly mediate all three outcomes. The Positive/Disorganized factor mediated effects only on global functioning and ASD traits.
CONCLUSION: Negative-expressive symptoms represent a core pathway linking cognitive deficits to functional impairment in 22q11DS, while motivational and positive symptom dimensions contribute differentially across functional domains. Expressive and motivational symptoms may represent candidate targets for future longitudinal and intervention studies in 22q11DS.