New Study Provides Insight into Causes of Schizophrenia

New findings in the journal Neuron provide novel insight into the causes of schizophrenia, which have remained largely elusive until recently.

Healthy brain function depends on a precise balance between chemical signals that excite and inhibit nerve cell activity. In this study, an international team of researchers confirmed and expanded upon their previous findings that specific mutations disrupt that balance, contributing to schizophrenia.
________________________________________________________________________________________________________________________________________________________________

RELATED CONTENT
Study: Long-Term Depression Linked to Schizophrenia
OCD Linked to Higher Risk of Schizophrenia
________________________________________________________________________________________________________________________________________________________________

“The present study strongly supports an etiological role for the disruption of excitatory, glutamatergic signaling and provides novel evidence implicating the disruption of inhibitory, GABAergic signaling in schizophrenia,” says lead study author Andrew Pocklington, PhD, a senior lecturer in the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University in Wales.

The researchers believe uncovering this significant piece of the puzzle may go a long way in helping to discover more about the complex architecture of schizophrenia.

“The robust confirmation that disruption of excitatory signaling contributes to schizophrenia makes this the first disease-related process to be convincingly identified,” Pocklington says. “However, this is only the first step towards building a reliable model of the disease.”

He and his colleagues came to these conclusions by comparing the genetic data of 11,355 patients with schizophrenia against a control group of 16,416 people without the disorder.

They looked for copy number variants (CNVs)—mutations in which large stretches of DNA are either deleted or duplicated. When they compared the CNVs found in individuals with schizophrenia to those in the control group, the researchers determined that the mutations in people with the disorder tended to disrupt genes involved in signaling.

“In terms of the CNV contribution to schizophrenia, disruption of glutamatergic and GABAergic signaling is only part of the picture,” Pocklington says. “We also see independent enrichment in behavioral and neurodevelopmental gene sets, suggesting that additional subcellular processes relevant to the disorder remain to be identified.”

The team hopes that their work could eventually lead to novel methods of predicting a person’s risk of developing schizophrenia.

“The evidence for disruption of inhibitory signaling in schizophrenia obviously needs to be confirmed, and other biological processes contributing to disease risk remain to be identified,” he says. “We are planning to look at these questions in future work.”

—Colleen Mullarkey

Reference

Pocklington AJ, Rees E, Walters JT, Han J, Kavanagh DH, Chambert KD, et al. Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia. Neuron. 2015; 86(5):1203–14.