The genetics of hypnotizability (2025)

Jessie Markovits, MD
Stanford School of Medicine, Stanford, CA, USA

Correspondence: Jkittle@stanford.edu

Keywords: hypnotizability, genetics, polymorphisms

Hypnotizability is a measurement of an individual’s ability to respond to standardized hypnotic suggestions on a validated scale. This trait remains relatively constant over time (Piccione et al., 1989) and exhibits concordance among twins (Bauman & Bul’, 1981) which indicates a possible genetic basis for hypnotizability. Hypnosis engages brain regions via neurotransmitters (Raz et al., 2006), prompting research into whether genetic differences in neurotransmitter function may predict hypnotizability.

Dopamine influences executive function, motor control, and motivation among other cognitive functions, and most genetic studies of hypnotizability focus on its key metabolizing enzyme, catechol-O-methyltransferase (COMT) (Acunzo et al., 2021). A single base-pair change in the DNA code for COMT, called a polymorphism, changes the activity of the enzyme which modifies dopamine levels in the brain. The COMT rs4680 (Val158Met) polymorphism affects enzyme activity and dopamine levels: Val/Val results in high activity and low dopamine, Met/Met in low activity and high dopamine, and Val/Met in intermediate levels of both. The relationship of this COMT polymorphism to hypnotizability is notably mixed, sometimes showing Val/Met associates with higher hypnotizability than Val/Val or Met/Met as in (Raz et al., 2006) whereas in other studies Val/Met exhibits intermediate hypnotizability while Val/Val was highest and Met/Met was lowest e.g., (Katonai et al., 2017) . Still others found no significant relationship (Bryant et al., 2013; Presciuttini et al., 2014) which led one group to propose that the dopamine-mediated theory of hypnotizability may be incorrect (Presciuttini et al., 2014). One small study used a model of four COMT polymorphisms that more accurately predicts enzyme activity (rs4680 plus rs6269, rs4633, and rs4818), and found a combination of two diplotypes that correlate with moderate dopamine levels in the brain and are positively correlated with hypnotizability (Cortade et al., 2023) This study may help explain the predictive failure of the single-SNP model if it can be further validated.

Single studies of polymorphisms in genes encoding the oxytocin receptor (OXTR) (Bryant et al., 2013), nitric oxide synthase 3 (NO3) enzyme (Presciuttini et al., 2009), and the opioid receptor mu 1 (OPRM1) (Presciuttini et al., 2018) have also shown some positive associations with hypnotizability levels and may be targets of future study. Other polymorphisms failed to show an association with hypnotizability including those in the serotonin-transporter-linked promoter region (5-HTTLPR) (Katonai et al., 2017), and that underpin various dopamine receptors (Raz et al., 2006).

Ultimately, there is no consensus in the field regarding the ability to use a single genetic test to predict hypnotizability, and most of the studies included small, exploratory sample sizes and have not yet been replicated. Future research analyzing larger sample sizes, and possibly sex, gene-gene, or gene-environment interactions could help clarify the relationship of genetics and hypnotizability. Further investigation into these genetic factors is warranted, since it could help to identify heightened or diminished susceptibility to hypnosis, providing a deeper understanding of the neurophysiology of the trait and its potential to be augmented or applied in therapeutic and experimental contexts.

References
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