This article is more than 5 years old. Information may no longer be current.

Chromosome 22 syndromes increase risk for psychiatric disorders

Individuals with 22q11.2 deletion or duplication were significantly more likely to develop a psychiatric disorder, according to recent findings.

“The clinical presentation of 22q11.2 [deletion syndrome] has been studied intensively and shown to be highly variable. More than 180 clinical features have been described, ranging from nearly healthy individuals to those with fatal conditions, such as immune deficiencies and congenital heart defects,” Louise K. Hoeffding, PhD, of Copenhagen University Hospital, Roskilde, Denmark, and colleagues wrote. “Psychiatric disorders have frequently been reported for the 22q11.2 [deletion syndrome], and multiple cross-sectional studies have indicated a high prevalence of schizophrenia. In addition, reports have highlighted the high frequency of both autism spectrum disorder, attention-deficit/hyperactivity disorder, and mood and anxiety disorders among individuals with the 22q11.2 deletion compared with the general population, but with inconsistent risk estimates between studies.”

To estimate incidence and risk for psychiatric disorders in individuals with 22q11.2 deletion or duplication, researchers analyzed a sample of 3,768,943 individuals born in Denmark from 1955 to 2012. Follow-up consisted of 57.1 million person-years. The cohort included 244 individuals with 22q11.2 deletion and 58 with 22q11.2 duplication.

Mean age at diagnosis of any psychiatric disorder was 12.5 years among individuals with deletions and 6.1 years among those with duplications.

Parental diagnosis of schizophrenia was associated with 22q11.2 deletion, while parental diagnosis of a psychiatric disorder other than schizophrenia was associated with duplication.

Individuals with 22q11.2 deletion (IRR = 4.24; 95% CI, 3.07-5.67) and duplication (IRR = 4.99; 95% CI, 1.79-10.72) had increased risk for psychiatric disorders.

Deletion (IRR = 34.08; 95% CI, 22.39-49.27) and duplication (IRR = 33.86; 95% CI, 8.42-87.87) were significantly associated with risk for intellectual disability.

Further, individuals with 22q11.2 deletion had increased risk for several psychiatric disorders, including pervasive developmental disorders (IRR = 9.45; 95% CI, 5.64-14.69) and childhood autism (IRR = 8.94; 95% CI, 3.21-19.23).

“The diagnosis of so many different psychiatric disorder categories in patients with 22q11.2 deletion and duplication points to the difficulties of using the ICD psychiatric diagnostic system criteria to make psychiatric diagnoses in children and adults with neurodevelopmental disorders of the developing brain,” James C. Harris, MD, of Johns Hopkins University School of Medicine, wrote in an accompanying editorial. “A more parsimonious approach is to instead systematically describe the behavioral phenotype of each neurogenetic syndrome and trace pathways from genes to behavior in these individuals. Genetic syndromes are not models for clinical ICD psychiatric disorders, per se. However, intermediate phenotypes identified in these patients can be beneficial in understanding features of disorders.” – by Amanda Oldt

Disclosure: Hoeffding and Harris report no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.