Background There is increased risk of developing psychosis in 22q11.2 deletion syndrome (22q11DS). Although this condition is associated with morphological brain abnormalities, simultaneous examination of multiple high-resolution measures of cortical structure has not been performed. Methods 53 patients with 22q11DS, 30 with psychotic symptoms, were compared to demographically matched nondeleted youths: 53 typically developing and 53 with psychotic symptoms. High-resolution MRI measures of cerebral volume, cortical thickness, surface area, and an index of local gyrification (lGI) were obtained and compared between groups. Results Patients with 22q11DS demonstrated global increases in cortical thickness associated with reductions in surface area, reduced lGI, and lower cerebral volumes relative to typically developing controls. Findings were principally in the frontal lobe, superior parietal lobes, and in the paramedian cerebral cortex. Focally decreased thickness was seen in the superior temporal gyrus and posterior cingulate cortex in 22q11DS relative to nondeleted groups. Patterns between nondeleted participants with psychotic symptoms and 22q11DS were similar, but with important differences in several regions implicated in schizophrenia. Post hoc analysis suggested that like the 22q11DS group, cortical thickness in nondeleted individuals with psychotic symptoms differed from typically developing controls in the superior frontal gyrus and superior temporal gyrus, two regions previously linked to schizophrenia. Conclusions Simultaneous examination of multiple measures of cerebral architecture demonstrates that differences in 22q11DS localize to regions of the frontal, superior parietal, superior temporal, and paramidline cerebral cortex. The overlapping patterns between nondeleted participants with psychotic symptoms and 22q11DS suggest partially shared neuroanatomic substrates.

The 22q11.2 deletion syndrome (22q11DS) presents with medical and neuropsychiatric manifestations including neurocognitive deficits. Quantitative neurobehavioral measures linked to brain circuitry can help elucidate genetic mechanisms contributing to deficits. To establish the neurocognitive profile and neurocognitive “growth charts”, we compared cross-sectionally 137 individuals with 22q11DS ages 8–21 to 439 demographically matched non-deleted individuals with developmental delay (DD) and medical comorbidities and 443 typically developing (TD) participants. We administered a computerized neurocognitive battery that measures performance accuracy and speed in executive, episodic memory, complex cognition, social cognition and sensorimotor domains. The accuracy performance profile of 22q11DS showed greater impairment than DD, who were impaired relative to TD. Deficits in 22q11DS were most pronounced for face memory and social cognition, followed by complex cognition. Performance speed was similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in face memory and emotion identification. The growth chart, comparing neurocognitive age based on performance relative to chronological age, indicated that 22q11DS participants lagged behind both groups from the earliest age assessed. The lag ranged from less than a year to over three years depending on chronological age and neurocognitive domain. The greatest developmental lag across the age range was for social cognition and complex cognition, with the smallest for episodic memory and sensorimotor speed, where lags were similar to DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability that may underlie brain circuitry associated with deficits in several neuropsychiatric disorders and thereby help identify potential targets and developmental epochs optimal for intervention.

Background Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder with high rates of psychosis and other psychopathologies, but few studies discuss treatment. Our aim was to characterize the prevalence and treatment of major psychiatric illnesses in a well-characterized sample of individuals with 22q11DS. Method This was a cross-sectional study of 112 individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each participant was administered a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold psychosis, depression, mania, generalized and separation anxiety, obsessions/compulsions, inattention/hyperactivity and substance use. Histories of mental health care and current psychotropic treatment were obtained. Results Psychopathology was common, with 79% of individuals meeting diagnostic criteria for a disorder at the time of assessment. Diagnoses of psychosis were made in 11% of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced significant subthreshold symptoms. Peak occurrence of psychosis risk was during adolescence (62% of those aged 12–17 years). Criteria for a mood disorder were met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity disorder (ADHD) 31%. Mental health care had been received by 63% of individuals in their lifetime, but only 40% continued therapy and 39% used psychotropics. Antipsychotics were used by 42% of participants with psychosis and none of the participants with APS. Half of those at risk for psychosis were receiving no mental health care. Conclusions Psychopathology is common in 22q11DS but is not adequately treated or clinically followed. Particular attention should be paid to subthreshold psychotic symptoms, especially in adolescents.

Background Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and non-deleted (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) aged 9-24 were matched to 22q11DS (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 (SIPS), and for ADHD, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differ 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). Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but 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. GAF was similar in 22q11DS and ND, except among those with low total SIPS scores. Conclusions Individuals with 22q11DS share overarching similarities with ND 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.