Birth defect gene linked to mental illness in mouse study

Gene mutations that can cause major birth defects may also cause more subtle disruptions in the brain and contribute to psychiatric disorders, according to a study.

Researchers investigated the function of the Dact1 gene, which is involved in the formation of the nervous system and plays an important role in embryonic development. Dact1 mutations are known to cause a range of severe spinal cord and brain malformations in mice, some resembling the human condition spina bifida.

The team deleted Dact1 gene function in the brains of mice and found that nerve formation was affected, causing neuron growth and branching similar to that seen in mice with models of psychiatric disorders.

'When you delete this gene function after initial, early development — just eliminating it in neurons after they've formed — they migrate to the right place and their numbers are correct, but their morphology is a little off', said Dr Benjamin Cheyette at the University of California, San Francisco, who led the study. 'And that's very much in line with the kinds of pathology that people have been able to identify in psychiatric illness'.

The researchers deleted the Dact1 protein in just one group of nerve cells in the brain known as cortical interneurons. The genetically altered interneurons, despite being relatively normal in size and number and in the correct position in the brain, had significantly fewer synapses, connections with other nerve cells, and did not branch out in the same way as cells with normal Dact1 function.

Cortical interneurons regulate activity in the cerebral cortex, including cognitive and sensory processes. Poor function of interneurons has been linked to several psychiatric conditions, including autism, schizophrenia and bipolar disorder.

The group are conducting research into the Wnt pathway, a cell signalling pathway that the Dact1 gene affects, in people with autism. The team also plan to perform behavioural experiments with the mice to test whether they have abnormalities in sociability, sensory perception, anxiety or motivation that resemble symptoms in major psychiatric disorders.