Ultra High Risk Status and Transition to Psychosis in 22q11.2 Deletion Syndrome

Abstract

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio-demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 6 17.6 months after initial assessment. Eighty-nine participants with 22q11DS (age range: 8-30 years; mean 16.1 6 4.7) were assessed using the Structured Interview for Psychosis-Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non-UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high-risk samples. Nevertheless, the relatively high transition rate in non-UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth. . This syndrome is characterized in most cases by a microdeletion of 3 million base pairs on chromosome 22 band q11, and has an estimated prevalence of 1:2.000-4.000 live births 6 . From a clinical perspective, 22q11DS is associated with high rates of psychiatric disorders, especially schizophrenia 7 . While 23 to 45% of affected adolescents report transient psychotic experiences [8][9][10][11] , up to 40% of affected adults are diagnosed with a psychotic disorder 7 . Moreover, 22q11DS was found in 0.3 to 2.0% of patients with schizophrenia [12][13][14] , with rates of up to 5.7% in patients with childhood-onset schizophrenia 15 . Taken together, these findings indicate that 22q11DS is a highly relevant genetic risk factor for schizophrenia and the most promising human model for studying risk factors and states at risk for schizophrenia 5 .Several studies have investigated prodromal symptoms in patients with 22q11DS, reporting rates between 45 and 56% for UHR symptoms and between 10 and 21% for UHR criteria (including frequency and onset/worsening requirements) 8,10,11,[16][17][18] . Armando et al 8 compared the symptom profile of UHR patients with (N530) vs. without (N581) 22q11DS and found no significant group difference in positive symptoms, while negative symptoms were more severe in patients with 22q11DS. Yet, few stud...