Genetic Links Found Between Endometriosis and Psychiatric Disorders

Endometriosis was associated with several psychiatric disorders through genetic and phenotypic mechanisms, even after accounting for several comorbidities including chronic pain, according to a genetic association study.

A multivariate regression analysis of more than 200,000 women found that endometriosis was associated with depression, anxiety, and eating disorders through a pleiotropic mechanism, even after accounting for age, body mass index, socioeconomic status, and chronic pain-related phenotypes, reported Dora Koller, PhD, MSc, of Yale School of Medicine and the Veterans Affairs Connecticut Healthcare Center in West Haven, Connecticut, and colleagues.

As shown in their study in JAMA Network Open, endometriosis was associated with increased odds of depression (OR 3.61, 95% CI 3.32-3.92), eating disorders (OR 2.94, 95% CI 1.96-4.41), and anxiety (OR 2.61, 95% CI 2.30-2.97).

A 1-sample mendelian randomization showed that the genetic liabilities to depression (OR 1.09, 95% CI 1.08-1.11) and anxiety (OR 1.39, 95% CI 1.13-1.65), though not eating disorders, were associated with higher odds of endometriosis.

"The main takeaway is that we found genetic and epidemiological evidence that endometriosis not only affects physical health but also mental health, and chronic pain is not the sole factor explaining this association," Koller told MedPage Today.

"It's expected that chronic pain causes depression, anxiety, and eating disorders, but we know it's not only because of that," Koller said. "There are some biological mechanisms which are causal, probably for both endometriosis and the mental health conditions."

Co-author Renato Polimanti, PhD, MSc, also of Yale School of Medicine and the VA Connecticut Healthcare Center, noted that the results reinforce the complex nature of endometriosis and its associations with mental health disorders as well as other comorbidities, such as chronic pain.

"One thing that we hope for with this study is [to add] to the knowledge about the complexity of endometriosis from a mental health perspective, but also highlight that endometriosis is unfortunately a really common disease," Polimanti told MedPage Today, adding that an estimated 10% of women worldwide develop the condition.

The complex nature of the disease is further exacerbated by the incomplete understanding of how it presents in patients, according to Louise Perkins King, MD, JD, of Brigham and Women's Hospital in Boston, who was not involved in the research.

"The biggest confounder here is that so many endometriosis patients have their disease poorly treated," she told MedPage Today.

She noted that in her experience with endometriosis patients, chronic pain is the biggest factor for depression, and treating patients with endometriosis for chronic pain often also improves their mental health.

The results are also important for increasing understanding around this "poorly diagnosed disease" with limited treatment options, King added. "It's a cart-and-horse, egg-and-chicken kind of thing. Are people with endometriosis, especially endometriosis with pain, at more risk for depression -- because anybody with chronic pain is exceptionally at risk for depression -- or not?"

King said that for many individuals with endometriosis, it can take 7 to 10 years before they are diagnosed, and in some cases patients undergo incorrect treatments before finally getting the necessary care.

"All of that experience is going to obviously, for many people, lead to depression, whether they are genetically predisposed or not," King said.

The researchers highlighted these limitations in the paper, writing that "the phenotypic associations observed may be affected by the fact that individuals diagnosed with a chronic disease often have more hospital visits than those without any chronic disease."

In addition, the authors noted, this limitation was unlikely to completely explain the large association between endometriosis and psychiatric disorders, since endometriosis remains "systematically" underdiagnosed.

In total, the team analyzed data on 8,276 women with endometriosis (mean age 53.1 years [SD 7.9]) and 194,000 women in a control group (mean age 56.7 years [7.9]) from Sept. 13, 2021 to June 24, 2022. Of the patients with endometriosis, 4,998 were identified using ICD-10 codes on their electronic health records and 4,300 were identified based on self-reported diagnoses (1,022 participants had both ICD-10 codes and self-reported diagnoses of endometriosis).

The researchers also conducted a genome-wide analysis of associations between endometriosis and psychiatric disorders. That analysis identified a genetic marker (DGKB rs12666606) that showed evidence of a pleiotropic association between endometriosis and depression (z score -9.46 for endometriosis, z score 8.10 for depression, P=5.56 × 10^-8; false discovery rate q=4.95 × 10^-4).

"This eventually could lead to better prevention and treatment strategies," Koller said. "A patient with endometriosis goes to the gynecologist [and] the gynecologist is aware that these psychiatric comorbidities can actually happen -- and they are really common among patients with endometriosis."

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