Genomics, the mind and the gut

Relation

Han CJ, Kohen R, Jun S, et al. COMT Val158 Met polymorphism and symptom improvement following a cognitively focused intervention for irritable bowel syndrome.Nurs Res. 2017;66(2):75-84.

Draft

Secondary genomic analysis of 2 previous randomized controlled trials comparing a nurse-led cognitive behavioral therapy (CBT) package with usual care for irritable bowel syndrome (IBS)

Participant

A total of 172 participants (from 2 previous studies) diagnosed with IBS and eligible for catecholO-Methyltransferase (COMT)genetic data was available. The sample was 87% female; 29% of participants had constipation-predominant IBS, 54% had diarrhea-predominant IBS, 11% had mixed presentation, and 6% had an unknown IBS subtype.

Study parameters assessed

IBS symptoms, psychological distress, quality of life and cognitive beliefs about IBS

intervention

Nurse-delivered IBS-focused CBT package. This included self-work on a CBT for IBS workbook¹and checking in with nurses throughout the study for 8 to 9 sessions (60 minute sessions) over 10 to 12 weeks. Concepts covered included recognizing dietary triggers, relaxation techniques, problem solving, correcting false beliefs, managing pain, and practicing good sleep habits.

Primary outcome measures

percentage of days with moderate to severe abdominal pain or discomfort, depression, anxiety, and feelings of stress; Secondary measurements included daily gastrointestinal symptoms, Brief Symptom Inventory (retrospective assessment of psychological distress), IBS-QoL Scale (quality of life), and Cognitive Scale for Functional Bowel Disorders (cognitive beliefs about IBS).

Symptoms were measured 1 month before study entry, with assessments conducted at 3 and 6 months after study start.

Key insights

This is what the researchers found outCOMEStatus was statistically significantly associated with benefit from the CBT package. Especially those with at least 1 copy of the Val¹⁵⁸Met version of Single Nucleotide Polymorphism (SNP) saw greater improvement in her anxiety, stress, abdominal bloat, constipation, and retrospective psychological distress after 3 months. This effect was not observed at the 6-month mark.

Practice implications

catecholO-Methyltransferase (COMT) is an important enzyme involved in the breakdown of the neurotransmitters dopamine and adrenaline. Val¹⁵⁸met is a common oneCOMEVariant, a single nucleotide polymorphism (SNP) in which the variant allele codes for methionine instead of valine at position 158^thAmino acid position. This leads to a functional difference in the COMT enzyme, resulting in a 30% decrease in enzymatic activity.²Your own statusCOMEAlleles (wild type or variant) have previously been associated with the effectiveness of CBT interventions.^3.4

The researchers found that COMT status was statistically significantly associated with CBT package benefit.

Genomic medicine has come under criticism⁵for the generally minimal clinical effects of individual SNPs. For this reason, many genomic medicine researchers are now turning to genetic risk scores consisting of a portfolio of SNPs.⁶However,COMEis an exception in that it is often still considered individually and is often taken into account in psychological interventions because of its connection to dopamine levels.

Two previous studies have shown that nurse-delivered cognitive behavioral therapy (CBT) is effective for irritable bowel syndrome.^7.8But the question remained: Do you have it?COMEStatus modulate the effect of this CBT approach in patients with IBS?

In this article, the authors found that a CBT package program for IBS was effective compared to usual care and was most effective in patients with at least one Val allele of common Val¹⁵⁸metCOMESNP. The current study found that this allele was most strongly associated with improving anxiety and stress, bloating, constipation, and subsequent psychological distress.

In general, this was a well-conducted study. It is registered on the US National Library of Medicine website ClinicalTrials.gov, reducing the risk of selective outcome reporting bias. There are also some limitations to the study. They didn't use standard IBS scales, making it difficult to understand the magnitude of the effect, and they only looked at people with European-American genetic ancestry. They did this to avoid potential bias problems inherent in genomic medicine research, but it limits external validity when attempting to apply the results to patients with other genetic lineages.

As discussed above, the magnitude of the effect modulation is based onCOMEStatus in this study is difficult to assess, so recommending genetic testing based on these data alone may be overstatement. Nevertheless, I find this study clinically useful. Many of my patients already have theirsCOMEStatus identified by commercially available genetics companies. If I am already considering a CBT intervention for an IBS patient because the clinical scenario suggests a strong psychological component, knowing that they have a Val allele can inform my treatment decision. If this is the case, it is simple enough to refer the patient to the workbook used to deliver this particular CBT package, which is readily available in book and eBook form.¹

Detailed background on SNPs, genomic medicine and a video version of this overview are available here.