Background 22q11.2 Deletion Syndrome (22q11DS) confers strongly increased genetic risk for multiple psychiatric disorders. Similarly to the general population, rates of psychiatric comorbidity suggest that common disease mechanisms are shared across dimensions of psychopathology. Such pleiotropic disease mechanisms remain however currently unknown. We hypothesized that pituitary dysmaturation, indicative of HPA-axis dysregulation, could correlate to reduced tolerance to daily life stressors and reflect pleiotropic risk factor for psychopathology. Moreover HPA-axis dysregulation could affect atypical cortical and hippocampal development previously described in 22q11DS.