A comprehensive overview of neuropsychiatric symptoms in adolescents with 22q11.2 deletion syndrome

Abstract

Background: The 22q11.2 deletion syndrome (22q11DS) is associated with a variety of neuropsychiatric outcomes that vary across deletion carriers. We adopted a dimensional approach to provide a comprehensive overview of neuropsychiatric symptom expression in adolescents with 22q11DS and further our understanding of the observed phenotypical heterogeneity.

Methods: Participants were 208 adolescents with 22q11DS between 10 and 19 years old. Semi-structured clinical interviews and IQ tests were used to quantify symptom expression on multiple symptom dimensions, some reflecting DSM-IV diagnostic domains. We investigated symptom expression in those with and without a formal DSM-IV classification and examined between and within symptom dimensions. We used correlation analyses to explore associations between different symptom dimensions.

Results: We demonstrated inter-individual differences in symptom expression, both between and within neuropsychiatric symptom dimensions. On most symptom dimensions, more than 50% of adolescents expressed at least one clinically relevant symptom. In addition, a significant proportion of youth without a formal DSM-IV diagnosis reported clinically relevant symptoms (e.g. >85% of those without an ADHD diagnosis reported ADHD symptoms). The exploratory correlation analysis indicated mostly positive correlations between symptom dimensions.

Conclusions: The finding that most adolescents with 22q11DS express neuropsychiatric symptoms, even in the absence of a DSM-IV classification, has substantial ramifications for guiding adequate support. Findings may spur further research into the dimensional structure of neuropsychiatric symptoms in 22q11DS and aid in uncovering mechanisms that contribute to symptom expression. Ultimately, this provides leads to improve clinical care for 22q11DS and to understand phenotypical variation in other high-risk genetic variants.

Keywords: 22q11DS; dimensions; neurodevelopment; psychiatry; symptom expression.

Figure 1

Boxplot presenting the standardised scores (%) on the major symptom dimensions (bold) and minor symptom dimensions for adolescents with 22q11DS. Individual dots represent individual participants. Participants with the same score share overlapping dots. RRBI, repetitive restricted behaviours and stereotyped interests. Note: Area to the left of the striped line = normal range; area between striped and dotted line = subthreshold range; area to the right of the dotted line = clinical range

Figure 2

Results of Spearman correlation analyses, ranging from −1 (dark red) to +1 (dark blue), to explore the associations between scores on the minor symptom domains (*p < .05 after correction for multiple comparisons).