New hormone treatment for social anxiety

What happens in the brain of a person who suffers from social anxiety? Why do some minors experience new relationships perfectly normally while others of the same age face worry and fear in anticipation of being separated from their parents for a few hours?

It is known that boys and girls have a natural social preference for their familiar figures. However, at some point in their growth, this preference is reversed and they seek new social interactions. However, in some cases this change does not occur naturally and social disorders and avoidance behaviours develop, which can lead to more serious problems. Is there any physiological basis for this?

A team led by Félix Leroy, from the Institute of Neurosciences of Alicante (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University (UMH), in Spain, had already found, through research in mice, a response in a hormone that the brain produces naturally: corticotropin-releasing hormone (or CRH). His team demonstrated in 2023 that CRH, which is produced by neurons in the infralimbic cortex (where, among others, emotional expression and alertness are regulated), sends a signal to the rostral region of the lateral septum (a region that regulates motivated behaviors such as socializing or seeking food and safety), which suppresses social interactions with familiar mice.

This circuit, the scientists explain, contributes to reducing the preference for familiar relationships and increasing the predilection for social novelty shown by adult mice. In addition, the scientists saw that when the mice were two weeks old, they showed an increase in the density of infralimbic neurons that release CRH, which was directly related to a change in the development of social preference in young mice, which went from choosing familiar companions to new conspecifics.

Using a combination of electrophysiological, chemogenetic, optogenetic, calcium recording and gene silencing techniques, the team has shown that this hormone modulates socialisation preferences. According to the IN scientist, “our team has observed that, with the use of hormones, socialisation preferences can be modulated and interaction with new individuals can be favoured, thus facilitating the creation of new social bonds.” This response is of particular interest for treating disorders related to apathy, phobia or anxiety that some people may develop in unfamiliar social environments.

Extreme introversion, which involves avoiding socializing with other people, is a more common disorder than is commonly believed. (Illustration: Amazings / NCYT)

The discovery could be an initial step towards the development of treatments based on this natural substance, which has begun to be tested in phase 1 preclinical trials, as to date no side effects have been detected and the results are promising. It would represent an alternative to current treatments, which in the case of social anxiety disorder or avoidant personality disorder are based on behavioural therapy alone or combined with antidepressants or anxiolytics, which only partially improve symptoms and can cause adverse side effects. Currently, there is no drug against social anxiety disorder recommended by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

Researchers are negotiating with interested pharmaceutical companies to license the patent for the development of treatments based on this technology. This would be the first specific substance to treat social anxiety disorders, which would avoid the use of other non-specific synthetic drugs, as well as their adverse effects. (Source: CSIC)