Long stretches of DNA, from 1000 to several million base pairs, can be deleted or duplicated within a chromosome. These changes are known as copy number variants (CNVs). It is now recognised that eight CNVs are associated with schizophrenia. For a person carrying a CNV, their risk of developing schizophrenia is increased by 3-58 times compared to the general population. It is also known that approximately 2.5-5% of people suffering from schizophrenia will carry at least one of these CNVs.
A new paper by Danish researchers serves as an excellent introduction to this rapidly developing and fundamental topic. The authors detail the characteristics of each of the eight CNVs.
The effect of CNVs: Neurexin
The majority of the CNVs harbor multiple genes. The exception is deletion of a stretch of DNA which harbors a single gene coding for a protein called neurexin (NRXN)1.
Neurexin is a component which holds the two sides of a synapse together. When people talk about connectivity in the nervous system, they are talking about components like neurexin. Healthy information processing in the brain depends on healthy stable connections between neurons.
The effect of CNVs: The other seven
Researchers are beginning to understand how the the seven other CNVs might operate to confer risk for schizophrenia, and indeed many other psychiatric syndromes. A property known as pleitropy means that a genetic change actually confers risk for a range of disorders. The CNVs associated with schizophrenia are also risk factors for autism, ADHD, epilepsy and intellectual disability. Indeed, all eight schizophrenia CNVs confer risk for autism spectrum disorders (Table 1).
Using animal models, researchers can decipher how the CNVs alter brain and behviour since DNA stretches are conserved across mammalian species. Animal models of five of the eight schizophrenia CNVs are now available. Those CNVs have been shown to cause deficits in cognition, social behavior, information processing and synaptic plasticity.
Further developments in this area are bound to reveal much more detail about how altered neuronal dynamics give rise to schizophrenia and other major psychiatric syndromes.
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