Journal of Neural Transmission

, Volume 123, Issue 8, pp 823–839 | Cite as

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

Psychiatry and Preclinical Psychiatric Studies - Review Article


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.


Velo-cardio-facial syndrome Connectivity DTI Resting-state fMRI Schizophrenia 



This work is supported by the National Center of Competence in Research (NCCR) Synapsy-The Synaptic Bases of Mental Diseases (SNF) and by grants of the Swiss National Foundation to S. Eliez (324730_121996 and 324730_144260). Individual fellowships from the Swiss National Foundation of Science support Marie Schaer (#145760) and Elisa Scariati (#145250). We would like to thank Angeline Mihailov for the manuscript proof reading.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to report.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Office Médico-Pédagogique, Department of PsychiatryUniversity of GenevaGenève 8Switzerland
  2. 2.Stanford Cognitive and Systems Neuroscience LaboratoryStanford UniversityStanfordUSA
  3. 3.Department of Genetic Medicine and DevelopmentUniversity of GenevaGenevaSwitzerland

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