How might stress contribute to increased risk for schizophrenia in children with chromosome 22q11.2 deletion syndrome?

The most common human microdeletion occurs at chromosome 22q11.2. The associated syndrome (22q11.2DS) has a complex and variable phenotype with a high risk of schizophrenia. While the role of stress in the etiopathology of schizophrenia has been under investigation for over 30 years (Walker et al. 2008), the stress-diathesis model has yet to be investigated in children with 22q11.2DS. Children with 22q11.2DS face serious medical, behavioral, and socioemotional challenges from infancy into adulthood. Chronic stress elevates glucocorticoids, decreases immunocompetence, negatively impacts brain development and function, and is associated with psychiatric illness in adulthood. Drawing knowledge from the extant and well-developed anxiety and stress literature will provide invaluable insight into the complex etiopathology of schizophrenia in people with 22q11.2DS while suggesting possible early interventions. Childhood anxiety is treatable and stress coping skills can be developed thereby improving quality of life in the short-term and potentially mitigating the risk of developing psychosis.