New Device Predicts the Efficacy of Hypnosis Treatment for Pain

How likely you are to experience hypnosis—and how well hypnosis can work as a treatment for your pain—is a heritable¹ and stable² trait called hypnotizability. Efforts to uncover biomarkers of this trait have focused on single nucleotide polymorphisms (SNPs) found in the catechol-o-methyltransferase (COMT) gene. Since characterizing COMT SNPs could help predict the efficacy of hypnosis treatment for pain management, in their recent study published in the Journal of Molecular Diagnostics, Cortade et al. developed an inexpensive point-of-care (POC) molecular testing device for genotyping COMT SNPs using giant magnetoresistive (GMR) biosensors. The team also showed the device’s efficacy for phenotyping hypnotizability.³

What Do COMT SNPs Have to Do with Hypnotizability and Pain?

COMT modulates dopamine levels in the prefrontal cortex (PFC), which is the region of the brain that is most active during hypnosis. SNPs in the COMT gene correlate to hypnotizability as well as to pain and perioperative opioid use. Specifically, four SNPs in the COMT gene have been identified; these SNPs form a haploblock and together predict COMT enzymatic activity better than any single SNP alone.⁴ The four-SNP haploblock underlies two COMT diplotypes, which correlate to both of the following:⁵

1. Optimal COMT activity, with the SNPs underlying as much as a 25-fold difference in enzymatic activity
2. Moderate levels of tonic dopamine in the PFC, which is thought to correspond to optimal cognitive performance⁶

How Does a GMR Array Work?

The giant magnetoresistive effect is a phenomenon where the presence of a local magnetic field can significantly increase the electrical resistance of a material. The GMR arrays take advantage of this effect, detecting changes in the local magnetic field caused by the binding of streptavidin-coated magnetic nanoparticles to biotinylated analytes on the GMR surface. During their binding, there is a measurable change in the electrical resistance of the GMR sensors, which correlates to the analyte quantity in the sample.

Since GMR sensors are highly sensitive to changes in the magnetic field, they can detect analytes at ultra-low concentrations. Compared to traditional fluorescent methods, GMR sensors, therefore, have higher sensitivity for the target and lower sensitivity for sample impurities.

How Was the GMR Array Used to Study COMT Genotyping and Hypnotizability?

Using this GMR array technology, Cortade et al. developed a GMR assay to detect the four-SNP haploblock in the COMT gene from rapid genomic DNA (gDNA) collected from participants. Then, they investigated the association between the detected COMT diplotypes and hypnotizability in a retrospective study at Stanford University that analyzed three cohorts of participants assessed with the Hypnotic Induction Profile (HIP).

HIP is a validated, in-person assessment where a trained provider evaluates both biological and sensorimotor experiences of the participant and gives a final score—from zero to ten—corresponding with the lowest to highest hypnotic susceptibility, respectively. Participants who score higher than three on HIP were considered individuals who would benefit from hypnosis intervention for pain (“treatable category”).

The following three participant cohorts were examined:

1. 23 high and low hypnotizability participants from a previous study
2. 30 participants from a trial testing the efficacy of a remote compared to in-person version of HIP, where only data from the in-person participants was used
3. Nine participants from the experimental condition of a total knee arthroplasty (TKA) randomized controlled trial testing the efficacy of hypnosis (experimental condition)

gDNA samples for the first cohort had already been extracted from whole blood, and for the remaining cohorts, the researchers extracted them from salivary samples. They developed a combined PCR and GMR protocol for the multiplexed amplification and genotyping of the four COMT SNPs. For all four SNPs in 15 patient samples, pyrosequencing confirmed 100 percent accuracy of the multiplexed COMT GMR assay across 60 runs.

Can COMT Genotyping Be Used to Predict Hypnotizability?

The GMR assay could differentiate between optimal and suboptimal COMT diplotypes. Participants with the optimal COMT diplotype showed significantly higher HIP scores than those with the suboptimal COMT activity, with 89.5 percent being in the treatable category. Additionally, all females who had optimal COMT activity were in the treatable category, but this was not true for males.

Despite the strong associations between COMT diplotypes and hypnotizability, Cortade et al. caution that this biomarker captures only about 40 percent of people who could benefit from hypnosis. So while their assay can be used to select candidates, it should not be used to exclude any individuals from hypnotic therapy.

How Can the COMT GMR Array Be Used in the Clinic?

Cortade et al. have engineered an inexpensive, sensitive, and accurate POC device that performs fully multiplexed four-SNP COMT genotyping using a GMR array. This device reveals genetic polymorphisms controlling enzymatic activity (of COMT) in the PFC to identify a subset of highly hypnotizable individuals who also experience high perioperative pain.

Future studies with bigger cohorts and a more comprehensive biomarker panel are necessary to fully establish these links. But overall, in the clinic, this COMT GMR genotyping POC device can enable targeted hypnosis referrals as an effective, nonpharmacological treatment for pain management.

References:

1. https://psycnet.apa.org/doiLanding?doi=10.1037%2Fh0034854
2. https://www.tandfonline.com/doi/abs/10.1080/00207147408413004
3. https://www.jmdjournal.org/article/S1525-1578(23)00003-X/fulltext
4. https://academic.oup.com/hmg/article/14/1/135/2355796
5. https://www.science.org/doi/10.1126/science.1131262
6. https://www.biologicalpsychiatryjournal.com/article/S0006-3223(11)00278-2/fulltext