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Metabolic biomarkers are tied to the risk of developing a mental health condition in a new study. Image credit: piola666/Getty Images.
  • Researchers are interested in understanding what components they can use to identify people with a higher risk for anxiety, depression, and stress-related disorders.
  • One recent study found that higher blood sugar and triglyceride levels were associated with an increased future risk for depression, anxiety, and stress-related disorders.
  • In contrast, the study also found that higher levels of high-density lipoprotein or ‘good’ cholesterol were associated with a lower future risk for depression, anxiety, and stress-related disorders.

Some people are more likely than others to experience chronic mental health conditions like anxiety and depression. When doctors identify who is more at risk and find contributing factors, this can help deliver early treatment and reach positive health outcomes.

A study recently published in JAMA Network Open examined several biomarkers and how these were associated with participants’ risk for depression, anxiety, and stress-related disorders.

Researchers looked at data from over 211,000 participants. They found that higher levels of blood sugar and triglycerides — a type of blood fats — were associated with an increased risk for these mental illnesses 20 years before diagnosis.

In contrast, researchers found that having higher levels of “good” cholesterol seemed to offer protection against these mental illnesses.

The results point to the importance of monitoring these metabolic biomarkers and regular follow-up so people can receive prompt mental illness diagnoses.

Anxiety, depression, and stress-related disorders are common forms of mental illness that can make it harder for people to thrive in everyday situations.

Many risk factors may contribute to someone’s chances of developing these mental health conditions. The researchers who conducted the current study note that metabolic factors may contribute to their development, and they wanted to examine this relationship more closely.

The researchers included 211,200 participants from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort.

Participants did not have any mental disorders at baseline and had at least one measurement of the metabolic biomarkers the study authors were focusing on. Almost 90% of the study participants were born in Sweden, and the average age of participants at first blood sampling was just over 42.

Researchers measured blood sugar and a number of biomarkers that measure fat-related components, including total cholesterol, low-density lipoprotein or “bad” cholesterol, high-density lipoprotein or “good” cholesterol, and triglycerides.

Researchers followed up with participants for an average of 21 years, looking at the development of anxiety, depression, and stress-related disorders, such as acute stress disorder and post-traumatic stress disorder (PTSD).

Their analysis accounted for specific covariates, including socioeconomic status, country of birth, fasting status at blood measurement, age at blood measurement, and sex.

During the study, 16,256 participants received a depression, anxiety, or stress-related disorder diagnosis. The average age of diagnosis was 60.5 years. About 3,000 participants received diagnoses of depression and anxiety.

The study found that higher levels of blood sugar and triglycerides were associated with higher risk for all three mental disorders and higher levels of “good” cholesterol were associated with a decreased risk.

In their nested case-control analysis, researchers further found that participants with anxiety, depression, or stress-related disorders had higher levels of triglycerides, total cholesterol, and blood sugar during the twenty years before getting a psychiatric diagnosis.

Alex Dimitriu, MD, double board-certified in psychiatry and sleep medicine, and founder of Menlo Park Psychiatry & Sleep Medicine, who was not involved in the study, noted to Medical News Today:

“This was an interesting study. High levels of glucose and triglycerides and low levels of (healthy) HDL protein were associated with increased risk of depression, anxiety and stress-disorders… Elevations in glucose and triglycerides as well as lipid abnormalities, may be associated with autonomic dysregulation (high cortisol states). These markers may also be signs of elevated inflammation, which has also been associated with mental health conditions.”

While these findings are interesting, the research did have its limitations. First, it was conducted in a specific population, so the results may not be generalizable to other populations. Most study participants were also employed during recruitment, further making it difficult to generalize the findings.

Future studies could include more diverse demographics in their samples to confirm this study’s findings. One sensitivity analysis that examined specific biomarkers “through referral by outpatient care” found that higher levels of “bad” cholesterol and total cholesterol and other factors were associated with a decreased risk for mental illnesses.

The findings of this sensitivity analysis warrant further investigation, even though conclusions for blood sugar and triglycerides remained consistent with the study’s main findings.

Second, the researchers note there was the possibility for residual confounding, and they acknowledge that accounting for body mass index (BMI) in future studies could show variation in the results.

There was a further risk for detection bias because doctors were more likely to monitor individuals with abnormal biomarker levels.

There was also possible misclassification because of the resources researchers had to collect data on psychiatric disorders. For example, participants who did not seek treatment or only saw their primary provider would not have been classified as having a psychiatric disorder.

It is also possible that new diagnoses were exacerbations of disorders doctors had not previously diagnosed.

Cheng-Han Chen, MD, board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, who was not involved in the research, offered the following insights as well:

“As with all observational studies, the direction of causality cannot be determined; it might be that people at risk for developing depression and anxiety have underlying physiology that effect metabolic changes which increase glucose and triglyceride levels. The results might also be confounded by attributes such as obesity or physical inactivity that might relate both abnormal glucose/triglycerides and also the risk of developing depression and anxiety. For now, these findings highlight the complex relationship between cardiovascular risk factors and mental health.”

The study results indicate that controlling and monitoring certain metabolic markers may be helpful for more than just physical well-being. Even as research advances, people can work with medical professionals to ensure that components like cholesterol and blood sugar remain in healthy ranges.

Jared Braunstein, DO, a board-certified internist with Medical Offices of Manhattan, not involved in the research, advised MNT that “[t]he best thing people can do to decrease glucose and triglyceride levels while increasing [high-density lipoprotein cholesterol levels] is to eat more good fats like olive oil, nuts, avocados, salmon, tuna etc.”

“Taking omega-3 fish oil supplements helps too as well as more cardiovascular exercise. They must also avoid high fat foods like donuts, cookies, muffins, pies and fried foods,” he emphasized.

The study findings also point to the importance of physicians monitoring their patients to ensure proper diagnosis and treatment.

Braunstein noted that “[t]he clinical implications are that we as physicians should be on the lookout for depression and anxiety in patients with metabolic syndrome with low [high-density lipoprotein cholesterol levels] and high triglycerides and glucose levels.”