Tiny brain spines reveal schizophrenia risk early

Researchers published in eLife a method for automatically mapping and comparing the nanostructure of dendritic spines across mouse models of psychiatric disorders. They examined models of both schizophrenia and autism spectrum disorder (ASD). In schizophrenia models, there was an increase in small, underdeveloped spines. In ASD models, large spines were more abundant.

Spines are the contact points at which neurons receive incoming signals. Their size and number partly determine how well a synapse (the connection between neurons) functions. Disruptions in spine structure have long been linked to psychiatric conditions, but an objective, population-wide analysis had been lacking.

A gene behind the schizophrenia pattern

The researchers also used their analysis to search for the molecular cause of the schizophrenia-associated spine pattern. They found that the gene Ecrg4, which encodes small secretory peptides (proteins secreted by cells), was more active in the schizophrenia models. Follow-up experiments confirmed that this gene directly influences the dynamics and shape of small spines.

From a longevity perspective, synaptic decline, in which synapses progressively lose efficiency, is also a feature of aging brains. The idea that population-level spine analysis could provide an early signal may in principle extend to age-related synaptic deterioration. That goes beyond what this study directly demonstrates and should be read as an interpretation.

From mouse to human

This is mouse research, and psychiatric conditions in rodents are never fully equivalent to the human versions. But the methodological approach, automated population analysis of synaptic microstructure, could in future be applied to human tissue from brain banks, opening avenues for earlier diagnosis of synaptic disorders.

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