5-HT2A Receptor Could Be Target For Sociocognitive Deficits Therapy

The serotonin 2A receptor in the human brain is critically involved in the experience of the self and others, University of Zurich researchers report.

Their study found that LSD reduces the borders between these intertwined psychological mechanisms, and thereby affects social interactions. The results could contribute to new therapies for psychiatric disorders such as schizophrenia or depression.

Virtually all mental health disorders come with difficulties in interpersonal relations that in the long run negatively affect the progression of the disease. The associated health and social restrictions can only be marginally improved by current forms of therapy.

One of the reasons for this is that there has been very little research into the basic neurobiological principles and in particular the neurochemical mechanisms of these kinds of disorders.

A further symptom of various psychiatric disorders is distortions of self-experience. People suffering from mental disorders often show either an inflated or weakened sense of self.

Blurred Boundaries

Katrin Preller, who led the research team, explained;

“LSD blurs the boundaries between one’s own self and others during a social interactions.”

Together with Prof. Franz Vollenweider her team cooperated with the Max Planck Institute of Psychiatry in Munich on the study.

LSD reduced activity in the posterior cingulate cortex and the temporal cortex, brain areas

LSD reduced activity in the posterior cingulate cortex and the temporal cortex, brain areas important for establishing one’s sense of self.
Credit: Preller et al., JNeurosci (2018)

While lying in an fMRI scanner, study participants communicated with a virtual avatar by means of eye movements after having been administered a placebo, LSD, or LSD in combination with ketanserin.

“This allowed us to show that brain regions which are important for distinguishing between self and others were less active under the influence of LSD,” says Preller. “And this also changed social interactions.”

The researchers were also able to show that the LSD-induced changes were blocked by ketanserin indicating that the serotonin 2A receptor (5-HT2A receptor) plays a critical role in this mechanism.

Potential Pharmacological Therapies

The findings show that self-experience and social interaction are closely linked. Varying impairments of these intertwined processes could be the result of an impaired transfer of information mediated by the 5-HT2A receptor system.

This could be important for the development of new pharmacological therapies. For example, blocking this receptor in patients suffering from an incoherent sense of self such as schizophrenia could improve their symptoms as well as their social abilities.

On the other hand, stimulating this receptor could help patients who suffer from an increased self-focus, as is the case with depression, for example.

Katrin H. Preller, Leonhard Schilbach, Thomas Pokorny, Jan Flemming, Erich Seifritz, Franz X. Vollenweider
Role of the 5-HT2A receptor in self- and other-initiated social interaction in LSD-induced states — a pharmacological fMRI study
Journal of Neuroscience 19 March 2018, 1939-17; DOI: 10.1523/JNEUROSCI.1939-17.2018