Genetic Factors, Shared Environment and the Risk of Chronic Pain and Depression

Genetic factors and the environment patients share with their partner or spouse may determine their risk of developing chronic pain and help explain the association between chronic pain and depression.

Genetic factors and the environment patients share with their partner or spouse may determine their risk of developing chronic pain and help explain the association between chronic pain and depression, according to a study published on August 16 in PLoS Medicine.1

Chronic pain and major depressive disorder are highly prevalent comorbid conditions. Whether chronic pain leads to depression or depression causes chronic pain is not understood, Andrew M. McIntosh, MD, chairman of biological psychiatry at the University of Edinburgh in Scotland and study co-author told Clinical Pain Advisor. Future studies are needed to investigate the mechanisms underlying the association between the 2 disorders, Dr McIntosh said.

“There is a genetic relationship between the 2 disorders,” Dr McIntosh said. “The more genetic risk variants you carry for depression, the more likely you are to be in chronic pain.”

About 100 million Americans suffer from chronic pain, according to an Institute of Medicine report, while about 15.7 million adults aged 18 years or older in the US had at least 1 major depressive episode in 2014, according to the US National Institute of Mental Health. 

“Both chronic pain and depression we know have a genetic basis but we don’t really know what the genes are driving this. Any way you can chip apart the complex genetic architecture, the better you are able to identify individual genes,” David Glahn, PhD, a professor of psychiatry and psychology at Yale University School of Medicine in New Haven, Connecticut, who was not an author of the current paper, told Clinical Pain Advisor.

This research points to the need for genetic studies of chronic pain, in an endeavor to identify novel drug targets, Dr McIntosh said. The study also suggests that using spouses or partners as controls in studies may need to be re-examined as they may not be as independent as previously thought, he added.

Dr McIntosh and co-authors used data from Generation Scotland: Scottish Family Health Study (GS:SFHS) to estimate the contributions of genetic factors and shared environment to chronic pain and the correlation to major depressive disorder.

They also used data from 2 genome-wide association studies to test whether chronic pain had a polygenic architecture and whether genomic risk of chronic pain predicted psychiatric disorder and vice versa. The researchers then used GS:SFHS and data from the UK Biobank to test the genetic relationship and their associated phenotypes.

The researchers showed that chronic pain is a moderately heritable trait (heritability = 38.4%), significantly concordant with spouses (variance explained 18.7%), positively correlated with depression (P =.13) and has a tendency to cluster within families for genetic reasons (genetic correlation = 0.51).

Future studies need to focus on the genetics of pain and depression and identify the biological pathway(s), more so than genetic variations involved to help develop therapeutic targets, said Dr Glahn.

Other studies need to investigate ways in which genetics may be leveraged to identify a person’s risk of depression and chronic pain. Such knowledge would allow for early interventions, prior to the appearance of symptoms.

Summary and Clinical Applicability

Results from this study indicate that genetic factors and the environment patients share with their spouse or partner are risk factors for the development of chronic pain and at least partly underlie the association between depression and chronic pain.

A combination of variants in many different genes and the cumulative effects of genetic risk factors for depression raise a person’s risk of chronic pain. 

Limitations and Disclosures

Limitations include the relatively small polygenic risk score and effect sizes, as well as the chance that spouse effects could have occurred from assortative mating.

The study was funded by a Wellcome Trust Strategic grant.

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  1. McIntosh, AM, Hall LS, Zeng Y, et al. Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis. PLoS Med .13 (8): 2016 Aug 16. doi:10.1371/journal.pmed.1002090.
  2. Nicholl BI, Mackay D, Cullen B, et al. Chronic multisite pain in major depression and bipolar disorder: cross-sectional study of 149,611 participants in UK Biobank. BMC Psychiatry. 2014; 14:350. 2014 Dec 10. doi: 10.1186/s12888-014-0350-4. 
  3. Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research (2011). The National Academies Press. Available at: Accessed August 30, 2016.
  4. National Institute of Mental Health. Major Depression Among Adults. Available at: Accessed August 30, 2016.