CREB Gene vs Fear, Phobia and PTSD

The expression of the CREB gene may function as a switch to regulate fear and extinction learning. The findings could provide a new avenue of treatment for PTSD and other mental health disorders.

Fear and fear extinction learning (the gradual reduction of fear by repeated exposure to the feared object) are adaptive processes caused by molecular changes in specific brain circuits, and they’re perturbed in conditions such as anxiety and post-traumatic stress disorder.

Think of it like an unlocked course on Mario Kart Super Deluxe Edition: its a route pf fear and phobia you didnt know existed, but in order to complete the game you have to cross the finish line - otherwise you will only go round and round and round the same track again and again reliving the events, being hit by shells and mushrooms and all sorts until you reach the gold star.

Geneticists and neurologists work together to explore and unveil the more complex facets of what comprises brain behaviour, rather than just asking ye old psychiatrist. And what they are beginning to reveal is that the expression of a particular gene may function as a switch to regulate feelings of fear and its extinction. The findings point to a potential new target for diagnosing, treating, and preventing fear-related psychiatric illnesses.

The new research in question focuses on neurons in the central amygdala that produce a corticotropin-releasing hormone (Crh) and are involved in the brain’s response to threats. The scientists examined how different gene pathways are activated within Crh neurons after the expression or extinction of fear.

This precise analysis utilized a new cell-type-specific technology called translating ribosome affinity purification, or TRAP, to identify gene expression only within the Crh amygdala cells, and furthermore, what the results presently indicate is that there does exist a diverse gene network which is activated or inhibited by fear versus extinction learning.

And we're back with the mice, I'm afraid 🐭 Additional analyses demonstrated that fear extinction learning requires that Crh neurons reduce their expression of a regulatory gene named CREB, which codes for a protein called cAMP response-element binding protein. Indeed, overexpression of CREB in Crh neurons in mice increased their fear response.

CREB is well known to be involved in learning and memory, and these data suggest that it may act as a molecular switch that regulates expression of fear and its extinction. So the end goal here is to consider whether targeting CREB expression in Crh neurons in the brain’s amygdala may provide a better understanding of the mechanisms behind fear-based psychiatric illnesses and represent a promising treatment strategy.

Fear is one of the most basic emotions we all experience in response to trauma–and also one of the most complex to study. And as a neuroscientist / psychologist in the making with a history of depression, PTSD and anxiety, I am proud to support this latest research into how animal models’ brains process fear, which could provide important parallels in humans and lead to new ways to diagnose or treat disorders such as PTSD.


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