Gene (DIXDC1) mutations could cause psychiatric disease

Gene (DIXDC1) mutations could cause psychiatric disease

In a new research led by UC San Francisco, scientists find that mutations in a gene (DIXDC1) can change the way brain cells communicate and may dispose people to psychiatric diseases.

The finding is newly published in Molecular Psychiatry. Researchers conducted genetic analysis of more than 9,000 human psychiatric patients and mutant mice. They find that mutations in the gene DIXDC1 may act as a general risk factor for psychiatric disease.

Gene DIXDC1 is involved in brain development, and its mutation can interfere with the way the brain regulates connections between neurons.

Researchers find that this gene is a key piece of the WNT signaling pathway, which is active in tissues of the brain and interacts with gene DISC1.

Gene DISC1 has been implicated in schizophrenia, depression, bipolar disorder, and autism spectrum disorders.

Researchers first analyzed genomic data from 6,000 patients with autism spectrum disorders, 1,000 patients with bipolar disorder, and 2,500 patients with schizophrenia.

They found that disruptive mutations in the main neuronal form of DIXDC1 were present about 80% more often in psychiatric patients compared to healthy controls.

To understand how gene DIXDC1 mutations put normal brain function at risk, researchers then turned to mutant mice that lacked a functioning copy of the gene.

They found that though the mutant mice were normal in many ways, they exhibited heightened anxiety, loss of motivation, and reduced interest in social interactions. All of these were similar to symptoms in human psychiatric disorders.

Further analysis showed that neurons in the mutant mice had lower numbers of dendritic spines, an important part of the synapses that neurons use to communicate with one another.

Researchers suggest that WNT signaling can play a key role in driving psychiatric disease, and that it works through changes in synaptic communication between neurons.

This study is one key step towards a precision medicine understanding of what drives psychiatric disorders.

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Citation: Martin PM, et al. (2016). DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling. Molecular Psychiatry, published online. DOI: 10.1038/mp.2016.184.
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