New Links Between Inflammation, Menopause, and Depression, Research Finds

Two studies on depression from researchers at the University of Texas Southwestern Medical Center highlight potential risk factors that could add to depression screening.

The first, published in the Journal of Clinical Psychiatry, found that high levels of a specific inflammatory molecule known as GlycA are associated with more likelihood of depressive symptoms. Researchers noted that this link remained even after taking other factors into consideration, such as antidepressant use.

The second focused on menopause. Published in Maturitas, the study analyzed a group of 384 women who shared menopause-related symptoms, including hot flashes, physical changes, sexual issues, and mental health changes. It found that sexual symptoms may be predictive of depression, but other issues were not.

Both studies used the same data set, from the Dallas Heart Study, which has collected health and behavior information on over 6,000 participants for the past 20 years. Encompassing both men and women and multiple ethnic groups, that study includes blood assays, DNA sequence information, and imaging results, providing a wealth of data that allowed researchers to gather insights in unique ways for both of the recent studies.

Link to Inflammation

Currently, GlycA is not part of a depression screening, but given the latest results, the researchers believe it should be considered. They found that people with higher levels of the inflammatory molecule were significantly more likely to show higher scores on a test called the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR), which includes symptoms such as:

• Sleep difficulties, including insomnia or sleeping too much
• Changes in appetite
• Consistently feeling sad
• Sudden increase or decrease in weight
• Difficulty with concentration or decision making
• Low energy or feeling slowed down
• Thoughts of death or suicide
• Feeling restless
• Experiencing low self-worth

This isn’t the first time inflammation and depression have been linked. A study published in Frontiers in Immunology suggested inflammation can play a major role in the condition, as well as fatigue. Those researchers noted that one of the reasons antidepressants work is because they lower inflammation levels to some degree; that when inflammation is too high, it can lower treatment efficacy.

Your Brain on Inflammation

Depression isn’t the only potential mental outcome of excess inflammation, previous research has found.

For example, inflammation tied to excess weight can be particularly problematic, according to a study published in the Journal of Alzheimer's Disease that looked at blood flow and brain activity. Low cerebral blood flow has been associated with increased inflammation, and also linked to brain-related issues like dementia, ADHD, depression, bipolar disorder, schizophrenia, and other conditions.

That study found that those at higher weights, who had more inflammation, tended to have less cerebral blood flow, according to the study's lead author, Daniel Amen, MD, founder of Amen Clinics.

“The takeaway here is the inflammation can absolutely have a negative effect on the brain and its functions,” he says. “The connection with weight comes because fat cells increase inflammation and also store toxins, which can damage the brain.”

The good news is that healthy behaviors can lower inflammation levels and protect the brain, potentially lowering risks of depression, dementia, and other issues. Amen says weight maintenance is important, but so are other inflammation fighters like nutritious foods and regular exercise.

Menopause and Depression

In the other recent study, the QIDS-SR also was used, along with a menopause-specific questionnaire about quality-of-life issues, in which participants rate their agreement with 23 statements, including:

• I believe my work benefits society.
• My diet is not nutritionally sound.
• My mood is generally depressed.
• Most things that happen to me are out of my control.
• I am not content with my sexual life.
• I currently experience physical discomfort or pain during sexual activity.
• I expect that good things will happen in my life.

Scoring on the questionnaire falls into four domains: occupational, health, emotional, and sexual. In the recent research, those who scored low on the sexual domain had significantly more depression symptoms than those who did not.

With Change Comes Challenges

Although the study is helpful for pinpointing a specific area of struggle for women undergoing menopause, hormones also can play a role in depression during menopause and perimenopause, according to Jennifer Payne, MD, psychiatrist and director of the Women’s Mood Disorders Center at Johns Hopkins.

“The same hormones that control the menstrual cycle also influence serotonin, a brain chemical that regulates feelings of well-being,” she says. “When hormone levels drop, serotonin levels also fall, which contributes to increased irritability, anxiety, and sadness.”

Falling estrogen and progesterone levels can trigger mood swings and reduce a sense of resilience. For some women, this can set off a depressive episode, Payne adds.

Much like the lifestyle changes to lower inflammation, healthy habits like exercise can have a profound effect—before, during, and after menopause. For example, a study in the Journal of Clinical Nursing with postmenopausal women found significant improvements in moderate and even severe depression in participants who exercised for just six months.

Understanding risk factors like inflammation and menopause-related issues can be helpful for better depression screening, particularly since they may identify those at risk while they are still in the early stages of depressive symptoms.