Study Find Links Between Inflammation, Menopause, and Depressive Disorder

Summary: Study reports a link between levels of GlycA, an inflammatory molecule in the blood, and an increased risk of depression symptoms. Researchers also outline specific symptoms associated with menopause and an increased likelihood of developing depression.

Source: UT Southwestern

Recently published UT Southwestern research reveals new insights about risk factors for depression based on data from a landmark longitudinal study focused on heart disease.

One study, published in the Journal of Clinical Psychiatry, shows a link between an inflammatory molecule in the blood and a person’s likelihood of depressive symptoms. The other study, in the journal Maturitas, indicates which symptoms of menopause are most predictive of depression.

Both studies are based on data from the Dallas Heart Study (DHS), which since 2000 has tracked the health of thousands of participants with the goal of improving the diagnosis, prevention, and treatment of heart disease.

“The DHS dataset is an extraordinary resource at UT Southwestern,” says Sherwood Brown, M.D., Ph.D., senior author of both papers and professor of psychiatry and vice chair for clinical research at UTSW.

The first two years of the study, more than 6,000 residents of Dallas County completed a detailed medical survey; 3,500 of them, aged 30 to 65, provided blood samples and underwent imaging studies. The DHS put particular emphasis on recruiting a diverse group; more than half of all participants were African American and 17 percent were Hispanic.

In the process of collecting information, data useful for studying other medical conditions was amassed. Brown immediately saw the utility for the DHS data in his own work on depression.

Inflammation and depression

Depression is estimated to affect 4.4 percent of the world’s population, making it one of the leading causes of disability. Researchers have struggled to understand all the molecular changes in the body that accompany major depressive disorder. More than 20 years ago, clinicians found that a pro-inflammatory drug used to treat some diseases could cause depression. Since that time, researchers including Brown have wondered about the link between inflammatory molecules and depression.

To that end, Brown and Samara Huckvale – an undergraduate at Columbia University who as a high school student worked in Brown’s lab in 2019 through UT Southwestern’s STARS (Science Teacher Access to Resources at Southwestern) Summer Research Program – analyzed data on 3,033 adults who had provided blood samples and completed a depression screening questionnaire as part of the DHS. The STARS Program, begun in 1991, provides summer research opportunities to high school students.

They discovered that levels of GlycA, an inflammatory molecule that’s not routinely tested for in patients, correlated with the severity of depressive symptoms. Even after controlling for factors such as sex, ethnicity, antidepressant use, education, and body mass index, GlycA levels remained associated with depression severity.

“This study suggests that maybe we could predict or diagnose depression based on inflammatory scores,” says Huckvale, who aspires to be a chemist. “Or maybe eventually we’ll be able to design therapies that actually target this inflammation to treat depression.”

Brown, who holds the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research and the Aradine S. Ard Chair in Brain Science, adds that he’d like to study whether GlycA levels can predict how well a treatment for depression works or help guide the best antidepressants for particular patients. He’d also like to follow patients over time to gauge whether GlycA levels rise before or after the onset of depression symptoms.

Menopause and depression

In the Maturitas paper, Brown and his colleagues used DHS data to study menopausal women, a group known to have an increased risk of depression.

Previous studies have found a correlation between the most common symptoms of menopause – hot flashes, night sweats, and sleep disturbances – and the onset of depression. Menopause also causes sexual symptoms, including vaginal dryness and low libido, but few studies have looked at the association between these symptoms and depression.

In the study, Brown and colleagues analyzed DHS data on 384 women aged 37 to 73 years old who self-reported being in menopause. Sixty-four percent of the women were non-Hispanic Black, 26.8 percent were non-Hispanic white, and 9.11 percent were Hispanic.

“There are very different cultural and ethnic experiences around menopause, so it was important to us to look at a very diverse sample of women,” says Michael Xincheng Ji, co-first author of the study and a fourth-year UTSW medical student.

As part of the Dallas Heart Study, the women reported whether they had symptoms classically associated with menopause, which the researchers grouped into vasomotor, psychosocial, physical, or sexual symptoms. In addition, each woman completed the Quick Inventory of Depressive Symptomatology-Self Report survey (QIDS-SR), which gauged the presence of depression symptoms.

Study Find Links Between Inflammation, Menopause, and Depressive Disorder

Depression is estimated to affect 4.4 percent of the world’s population, making it one of the leading causes of disability. Image is in the public domain

The prevalence of sexual symptoms of menopause was positively associated with a higher score on the QIDS-SR. This association remained even after excluding women who were taking antidepressants, and there was also an association between psychosocial symptoms of menopause and the QIDS-SR score. No association was found between vasomotor or physical symptoms and the QIDS-SR score, and ethnicity was not a strong predictor of the depression symptoms.

“Recognizing patterns in who is most likely to develop depression is really important to help guide our screening efforts,” says Sydney Singleterry, co-first author of the new work and a fourth-year UTSW medical student.

“What we hope is that these findings make clinicians think about the possibility of depression when they hear a woman reporting these symptoms,” says Brown, also a member of the Peter O’Donnell Jr. Brain Institute.

Other UTSW researchers who contributed to the Journal of Clinical Psychiatry paper were Stephanie Reyes, Alexandra Kulikova, Anand Rohatgi, and Kayla Riggs.

Funding: The work was supported, in part, by the STARS program, the National Center for Advancing Translational Sciences (UL1TR001105), and the Donald W. Reynolds Cardiovascular Clinical Research Center.

Other UTSW researchers who contributed to the Maturitas study were Alexandra Kulikova, Yaprak Harrison, and Geetha Shivakumar. The research was supported by funds from the National Center for Advancing Translational Sciences (UL1TR001105).

About this depression research news

Source: UT SouthwesternContact: Press Office – UT Southwestern
Image: The image is in the public domain

Original Research: Closed access.
“An Association Between the Inflammatory Biomarker GlycA and Depressive Symptom Severity” by Samara Huckvale; Stephanie Reyes, MA; Alexandra Kulikova, MS; Anand Rohatgi, MD; Kayla A. Riggs, MD; and E. Sherwood Brown, MD, PhD. Journal of Clinical Psychiatry

Closed access:
“Association of menopause symptoms with depressive symptom severity in a diverse community-based sample” by E. Sherwood Brown et al. Maturitas


An Association Between the Inflammatory Biomarker GlycA and Depressive Symptom Severity

Objective: The underlying mechanisms of depression remain unclear; however, current literature suggests a relationship between inflammation and depression. The association between the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) and depression has been previously investigated, but the relationship between GlycA, a novel spectroscopic inflammatory biomarker, and depression does not appear to have been examined.

Methods: Data were obtained from The Dallas Heart Study (DHS, conducted between 2000 and 2002), which consisted of a large community-based sample of Dallas County residents (N = 3,033). Depressive symptom severity was assessed with the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR). It was hypothesized that the serum GlycA level would be a statistically significant predictor of QIDS-SR scores after control for demographic covariates. Multiple linear regression was used to assess the relationship between GlycA level and QIDS-SR scores. The role of hs-CRP in predicting QIDS-SR scores was also explored.

Results: GlycA level was a statistically significant positive predictor of QIDS-SR score (β = .053, P= .038) with control for sex, age, antidepressant use, ethnicity, smoking status, drinking status, body mass index, and years of education. In a subset of adults with moderate-to-severe depression, GlycA level was not associated with QIDS-SR scores. Additionally, hs-CRP level was not a statistically significant predictor of QIDS-SR scores.

Conclusions: This study found a positive association between the inflammatory biomarker GlycA, but not hs-CRP, and depressive symptom severity in a large multiethnic and multiracial community-based sample. Thus, these results provide the first indication that GlycA may be a potentially useful novel biomarker of depression.


Association of menopause symptoms with depressive symptom severity in a diverse community-based sample


  • •Sexual symptoms in menopause may be predictive of depression.
  • •Other menopausal symptoms were not significantly associated with depression.
  • •Race and ethnicity were not significant predictors of depression in menopause.


The Dallas Heart Study dataset was used to examine relationships between menopausal symptoms and depressive symptom severity in 384 women (37–73 years old) self-reporting as menopausal. Self-reported menopausal symptoms were grouped based on the Menopause-specific Quality of Life Questionnaire (MENQOL). Depressive symptom severity was assessed using the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). The relationship between menopause symptom groups, ethnicity and QIDS-SR was evaluated using multiple linear regression. Endorsement of sexual symptoms was positively associated with QIDS-SR score (β = .12, p = .031), suggesting that sexual dysfunction during menopause may be a predictor of underlying depressive symptoms.

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