Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis

December 9, 2022

Putting It Into Practice

Schizophrenia is a heterogeneous disorder that can be categorized into patients with positive, negative, and cognitive symptoms.

Similarly, the response to treatment is heterogeneous. Treatment response among patients with schizophrenia is determined by genetics (as demonstrated by the 1% concordance rate between unrelated individuals and the 44% concordance rate between monozygotic twins), the environment, and an interaction between genetics and the environment (as demonstrated by cytomegalovirus infection and the CNV near the CTNNA3 gene).

As the cost of whole genome sequencing decreases and the detection of single gene CNS improves, individualized treatment of patients with schizophrenia will become available in the clinical setting.

Why this study matters

Patients with schizophrenia have an increased CNV burden, including rare CNVs that significantly increase the risk of schizophrenia. Identification of specific genes that are associated with schizophrenia is necessary to elucidate the neurobiology and pathophysiology of the disease.

The current study expanded what is known about the genetics of schizophrenia and the phenotypic heterogeneity of the disease.

Study design

Using chromosomal microarray and whole exome sequencing, CNVs were identified in 509 patients with treatment-resistant psychoses.

Results and conclusion

Of the 509 patients, 47 (9.2%) had 1 or more CNVs known to have or possibly have a neuropsychiatric disorder risk, and 24 (4.7%) had a CNV with a known neuropsychiatric disorder risk. The prevalence of schizophrenia-associated CNVs was 4.1%.

The most frequent CNVs were duplicates (16p11.2 and 15q11.2-q13.1) and deletions (22q11.2). Duplication of 15q11.2-q13.1 was independently associated with treatment resistance.

Original Source