The Psychosis Spectrum in 22q11.2 Deletion Syndrome Is Comparable to That of Nondeleted Youths

Abstract

Background: Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and nondeleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity.

Methods: ND youths (n = 150) ages 9 to 24 years were matched to 22q11DS individuals (n = 150) on age and sex, stratifying for presence of psychosis spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes, and for attention-deficit/hyperactivity, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differs from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis.

Results: Onset of psychosis proneness was similar among 22q11DS (mean: 11.0 years) and ND (mean: 12.1 years) individuals. Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND individuals were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but it did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis spectrum 22q11DS; substance-related disorders were more likely in ND. Global assessment of function was similar in 22q11DS and ND individuals, except among those with low total Structured Interview for Prodromal Syndromes scores.

Conclusions: Individuals with 22q11DS share overarching similarities with ND individuals in psychosis symptoms and age of onset for psychosis proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis.

Keywords: 22q11.2 Deletion syndrome; Clinical high risk; DiGeorge syndrome; Prodromal; Psychosis; Schizophrenia.

Figure 1. SOPS Items Showing Differential Item Functioning

Compared to ND at the same total level of symptomatology, individuals with 22q11 are more likely to have clinically significant impairment in stress tolerance (G4), avolition (N2), and ideational richness (N5) while they are less likely to have unusual thought content (P1), persecutory ideas (P2), and bizarre thinking (D2). Y-axis illustrates probability of clinically significant symptoms for that item. X-axis represents the number of total clinically significant items endorsed by a participant. 22q11DS=22q11.2 deletion syndrome; ND=non-deleted; SOPS=scale of prodromal symptoms

Figure 2. Cognition in 22q11.2 Deletion Syndrome and Non-Deleted Individuals

Accuracy scores for 12 tasks assessing four cognitive domains (executive function, episodic memory, complex cognition, and social cognition) were normalized against ND individuals without psychosis-spectrum (n=56). Individuals with 22q11DS were significantly impaired in all cognitive domains as well as in the overall composite score compared to ND (p<0.001 for all comparisons). There were no differences between those with psychosis-spectrum versus those without for either 22q11DS or ND. Pairwise comparisons were made using Student's t-test with significance threshold p=0.05. Error bars represent 95% confidence intervals. 22q11DS=22q11.2 deletion syndrome; ND=non-deleted; +PS=with psychosis-spectrum; −PS=without psychosis-spectrum

Figure 3. Comorbidities of Psychosis-Spectrum Individuals with 22q11DS and ND

Mood disorders occur in similar prevalence, but individuals with 22q11DS who are psychosis-spectrum are more likely to have comorbid ADHD (p<0.01) and less likely to have comorbid substance disorders (p<0.01). Prevalence of comorbidities were compared using two-sided Student's t-test with significance threshold set at p=0.05. 22q11DS=22q11.2 deletion syndrome; ND=non-deleted; N.S.=non-significant; Mood=mood disorders including major depression, bipolar disorder, dysthymia, and unspecified depressive and mood disorders; ADHD=attention deficit hyperactivity disorder; Substance=abuse or dependence on alcohol or illicits including hallucinogens, opioids, anxiolytics, and cocaine.

Figure 4. Global Assessment of Function and Total SOPS Score

Mean GAF is plotted against total SOPS score for 22q11DS (blue) and ND participants (red). Total SOPS score was segmented into 4 groups, ranging from 0-10, 11-19, 20-30, and 31 and above. GAF=global assessment of function; SOPS=scale of prodromal symptoms; 22q11DS=22q11.2 deletion syndrome; ND=non-deleted.