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Impact of Psychiatric Comorbidity and Cognitive Deficit on Function in 22q11.2 Deletion Syndrome

J Clin Psychiatry 2015;76(10):e1262–e1270

Objective: Presence of psychiatric comorbidity is associated with poor functioning and is an important consideration in treatment. Many individuals with 22q11.2 deletion syndrome (22q11DS) develop comorbid psychiatric disorders, yet its pattern and impact on functioning have not been formally investigated. In this cross-sectional study, we examined the relationship between comorbid psychopathology and neurocognitive deficits and their association with global functioning. We hypothesized that higher psychiatric burden and psychosis-spectrum features would be associated with reduced functioning and increased neurocognitive deficits.

Method: The cohort included 171 individuals with 22q11DS and mean (SD) age of 17.4 (8.1) years, recruited from a tertiary children’s hospital and nationally through social media between September 2010 and December 2013. Psychiatric diagnoses and functioning were assessed using semistructured interviews and the Global Assessment of Functioning (GAF) scale, respectively. On the basis of psychopathology and number of comorbid diagnoses, participants were assigned to unaffected (n = 32), nonpsychosis spectrum (n = 24), nonpsychosis spectrum-plus (n = 15), psychosis spectrum (n = 29), and psychosis spectrum-plus (n = 71) groups. Executive function, episodic memory, complex cognition, social cognition, and praxis speed were assessed using a computerized neurocognitive battery (CNB). Cognitive profile and GAF scores were compared among the groups, and the association of GAF with cognitive performance and psychopathology was examined.

Results: We observed high rates of comorbid psychiatric disorders. Approximately 50% of the participants had 2 diagnoses. Psychosis spectrum disorders were most frequently comorbid with other disorders. GAF score was progressively worse with increased psychiatric burden. Mean (SD) GAF score for the unaffected group (81.1 [8.9]) was significantly different from those of nonpsychosis spectrum (68.6 [12.1]), nonpsychosis spectrum-plus (63.4 [8.8]), psychosis spectrum (58.7 [13.1]), or psychosis spectrum-plus (55.5 [13.3]) (P < .05) groups. All groups performed poorly and were comparable to each other on the CNB (P = .273). Notably, verbal memory (P = .003), spatial processing (P = .001), and parent education level (P < .001) were significantly associated with GAF.

Conclusions: Individuals with 22q11DS have high rates of comorbid psychiatric disorders and diffuse cognitive deficits regardless of psychiatric burden. Those with psychotic spectrum disorders and comorbid psychiatric disorders are at an increased risk for poor overall functioning.