Alteration of functional brain architecture in 22q11.2 deletion syndrome - Insights into susceptibility for psychosis

Abstract

The 22q11.2 deletion is one of the most common copy number variants in humans. Carriers of the deletion have a markedly increased risk for neurodevelopmental brain disorders, including schizophrenia, autism spectrum disorders, and attention deficit hyperactivity disorder. The high risk of psychiatric disorders associated with 22q11.2 deletion syndrome offers a unique possibility to identify the functional abnormalities that precede the emergence of psychosis. Carriers of a 22q11.2 deletion show a broad range of sensory processing and cognitive abnormalities similar as in schizophrenia, such as auditory and visual sensory processing, response inhibition, working memory, social cognition, reward processing and arithmetic processing. All these processes have a significant negative impact on daily life if impaired and have been studied extensively in schizophrenia using task-based functional neuroimaging. Here, we review task-related functional brain mapping studies that have used electroencephalography or functional magnetic resonance imaging to identify functional alterations in carriers with 22q11.2 deletion syndrome within the above mentioned cognitive and sensory domains. We discuss how the identification of functional changes at the brain system level can advance the general understanding of which neurobiological alterations set the frame for the emergence of neurodevelopmental disorders in the human brain. The task-based functional neuroimaging literature shows conflicting results in many domains. Nevertheless, consistent similarities between 22q11.2 deletion syndrome and schizophrenia have been found for sensory processing, social cognition and working memory. We discuss these functional brain alterations in terms of potential biomarkers of increased risk for psychosis in the general population.