Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome

E. Scariati, M. C. Padula, M. Schaer, S. Eliez

Patients affected by 22q11.2 deletion syndrome (22q11DS) present a characteristic cognitive and psychiatric profile and have a genetic predisposition to develop schizophrenia. Although brain morphological alterations have been shown in the syndrome, they do not entirely account for the complex clinical picture of the patients with 22q11DS and for their high risk of psychotic symptoms. Since Friston proposed the "disconnection hypothesis" in 1998, schizophrenia is commonly considered as a disorder of brain connectivity. In this study, we review existing evidence pointing to altered brain structural and functional connectivity in 22q11DS, with a specific focus on the role of dysconnectivity in the emergence of psychotic symptoms. We show that widespread alterations of structural and functional connectivity have been described in association with 22q11DS. Moreover, alterations involving long-range association tracts as well as midline structures, such as the corpus callosum and the cingulate gyrus, have been associated with psychotic symptoms in this population. These results suggest common mechanisms for schizophrenia in syndromic and non-syndromic populations. Future directions for investigations are also discussed.