Evidence for a common biological basis of the absorption trait, hallucinogen effects, and positive symptoms: Epistasis between 5-HT2a and COMT polymorphisms

The personality trait Absorption—a disposition for altered states of consciousness involving focused attention, vivid imagery, and mystical experiences—is linked to a specific genetic variation. People with the T/T genotype of the T102C polymorphism in the 5-HT2a receptor gene, which produces stronger receptor binding, scored significantly higher on the Tellegen Absorption Scale. No independent effect was found for the COMT gene variation, but an interaction between the two genes was significant, highlighting the interplay between serotonin and dopamine systems. These results suggest a biological basis for Absorption.

Study at a glance

Abstract

Absorption represents a disposition to experience altered states of consciousness characterized by intensively focused attention. It is correlated with hypnotic susceptibility and includes phenomena ranging from vivid perceptions and imaginations to mystical experiences. Based on the assumption that drug-induced and naturally occurring mystical experiences share common neural mechanisms, we hypothesized that Absorption is influenced by the T102C polymorphism affecting the 5-HT2a receptor, which is known to be an important target site of hallucinogens like LSD. Based on the pivotal role ascribed to the prefrontal executive control network for absorbed attention and positive symptoms in schizophrenia, it was further hypothesized that Absorption is associated with the VAL158MET polymorphism of the catechol-O-methyltransferase (COMT) gene affecting the dopaminergic neurotransmitter system. The Tellegen Absorption Scale was administered to 336 subjects (95 male, 241 female). Statistical analysis revealed that the group with the T/T genotype of the T102C polymorphism, implying a stronger binding potential of the 5-HT2a receptor, indeed had significantly higher Absorption scores (F = 10.00, P = 0.002), while no main effect was found for the COMT polymorphism. However, the interaction between T102C and COMT genotypes yielded significance (F = 3.89; P = 0.049), underlining the known functional interaction between the 5-HT and the dopaminergic system. These findings point to biological foundations of the personality trait of Absorption.