New research sheds light on the role of Cacna1c in psychiatric disorders

Genetic variation in the gene Cacna1c has been consistently associated with increasing risk for psychiatric disorders, particularly schizophrenia and bipolar disorder. It is therefore important to try and understand how this gene may increase risk and the impact it may have on biological pathways.

Research Associate Anna Moon recently published the results of a study utilising Cacna1c hemizygous rats (where one copy of a gene is knocked out, with one copy remaining), where research concentrated on how their behaviour and biology differ to wild-type rats. This particular study looked at how these rats learn, a highly important area to study as many people with schizophrenia and related psychiatric disorders show altered learning, particularly associative learning.

Associative learning is an important form of learning – most people are familiar with this due to Pavlov’s research in the 1920s. It involves learning that one stimulus predicts a particular outcome, for example, a ‘click’ sound predicts that food will be delivered. In this study, the authors showed that rats hemizygous for Cacna1c learn associations in a different manner than their wild-type counterparts. Instead of learning that one stimulus predicted an outcome, they associated the outcome with a number of different, irrelevant cues that occurred within their environment. This increased association to so-called ‘inappropriate’ cues or stimuli is known as aberrant salience and is often reported in patients with psychosis.

Anna Moon said, ‘Understanding the role of Cacna1c is very important to the research community as it has been consistently implicated in psychiatric disorders, but we don’t yet fully understand why. These results indicate a potential mechanism through which variation in Cacna1c may have behavioural outcomes consistent with key models of psychosis. If we can fully pick out the role of this gene and how it can increase risk, it would help inform on pathways or targets for future therapy’.

This result is important, as it suggests Cacna1c may be highly important for regulating learning processes, which are altered in a wide-range of mental disorders. It particularly suggests that more research into this gene’s role within psychosis would be advantageous to understanding the molecular basis of this phenomena.

Please find the full research paper here, published in Schizophrenia Bulletin:

https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.1093/schbul/sbz127/5698064