A highly increased risk of schizophrenia spectrum disorders in 22q11.2 deletion carriers

Vangkilde A, Olsen L, Hoeffding LK, Pedersen CB, Mortensen PB, Werge T, Trabjerg B.
Schizophr Bull. 2016 May;42(3):824-31.

Although studies have indicated that there is a high risk for schizophrenia in individuals with 22q11.2 Deletion Syndrome, the population based risk of schizophrenia in individuals with 22q11.2 deletion prior to onset of schizophrenia is not known.

Vangkilde and colleagues, using information recorded in the nationwide Danish Psychiatric Central Register and the Danish Cytogenetic Central Register, examined the incidence rate ratios (IRR) of schizophrenia in known carriers of a 22q11.2 deletion compared to non carriers in the entire Danish population as well as the impact of a range of other potential confounders (i..e, parental history of mental illneses, urbanicity, parental age and immigration status) that are known to predispose to schizophrenia.

Out of 3107281 people born in Denmark between 1955 and 2003, 156 were identified with 22q11.2DS. The majority of them received the 22q11.2DS diagnosis between 10 and 25 years old. Among these, 6 developed schizophrenia-spectrum disorder after the 22q11.2DS diagnoses while 3 were diagnosed with schizophrenia-spectrum disorder before they were tested for 22q11.2DS. These 3 individuals were excluded from the analyses as including them would distort the estimation of the IRR.

Individuals with 22q11.2DS had an IR of schizophrenia spectrum diagnosis of 57.8 per 10000 person years (i.e., years of observation time per person) in comparison to 6.56 among persons without the 22q11.2 deletion and an overall 8.13-fold increased risk of schizophrenia spectrum disorder compared to persons without 22q11.2DS. Apart from 22q11.2 status, age (15-25), having parents with a psychiatric diagnosis are well as parents born abroad also increased the IRs. When the analysis was restricted to individuals with 22q11.2DS who were diagnosed with schizophrenia (n=4), individuals with 22q11.2DS had an overall 11.11 fold increased risk of schizophrenia compared to non-deleted individuals.

This is the first nationwide study to examine the risk of developing schizophrenia in individuals with 22q11.2DS while also taking into account potential confounders. The findings provided further support that the 22q11.2 deletion confers high risk for schizophrenia.

Author information:
Dr Maria Niarchou
Research Associate
Division of Psychological Medicine and Clinical Neurosciences
Cardiff University
CF10 3AT