Psychology Chartered

Schizophrenia: Resynchronising and Restoring Brain Dynamics

Posted by Lexi Nye

1st October 2018

New research has sparked a viable treatment route for schizophrenia! 

Current treatments for schizophrenia include atypical antipsychotics which target the dopaminergic and serotonergic systems. Although these are found highly effective for managing many schizophrenic symptoms, such as delusions, these atypical antipsychotics are argued to not be as effective for improving cognitive symptoms, for example poor working memory (Wang, Hu, Guo, Wu, Li & Zhao, 2013).

This new study therefore aimed to improve the cognitive symptoms of schizophrenia through a mouse model by looking at a brain structure strongly involved in memory; the hippocampus.

Mice were genetically engineered to have a deletion on the mouse chromosome 16 to replicate the chromosomal deletion of the human 22q11 deletion syndrome– which is currently the highest identified genetic risk for developing schizophrenia.

Even though deletion syndrome is a neurodevelopmental disorder, this new study explored whether pharmacological treatments could, in effect, ‘resynchronise’ the neural networks affected.

Networks

The thousands of neurons in the hippocampal networks of the ‘control’ mice were found to be in synchronisation and perfectly organised. In stark contrast, the neural networks in the mouse model were found to be uncoordinated and desynchronised.

Why was this? These mice were found to show hypoexcitability of a particular group of inhibitory neurons, called Parvalbumin Interneruons (PVIs), whose role is to regulate and optimally pattern network activity in the hippocampus. This research then begged the question: if we increase the activity of these inhibitory neurons, will they start to regulate the affected network dynamics?

Resynchronising

The answer was yes! By increasing the excitability of the PVIs with pharmacological treatments, the network desynchronization was successfully extinguished. Not only this, but behavioural schizophrenic symptoms such as working memory were improved as well as a reduction in hyper-locomotor activity.

Treatment

By targeting these PVIs the neural networks were restored, which paves a really exciting new therapeutic treatment for 22q11DS. This will not only help individuals with schizophrenia but can also apply to various other mental health disorders which originate from this genetic syndrome such as autism-spectrum disorders and attention deficit/hyperactivity disorders!

 

 

 

References

Marissal, T., Salazar, R. F., Bertollini, C., Mutel, S., De Roo, M., Rodriguez, I., … & Carleton, A. (2018). Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia. Nature neuroscience, 1.

Wang, J., Hu, M., Guo, X., Wu, R., Li, L., & Zhao, J. (2013). Cognitive effects of atypical antipsychotic drugs in first-episode drug-naïve schizophrenic patients. Neural Regeneration Research8(3), 277–286. http://doi.org/10.3969/j.issn.1673-5374.2013.03.011