High glucose and TG levels and low HDL-C levels tied to risk of depression, anxiety, and stress-related disorders: JAMA

The population-based cohort study of more than 200,000 individuals revealed that high levels of triglycerides and glucose and a low level of high-density lipoprotein (HDL) were associated with a higher risk of anxiety, depression, and stress-related disorders. The findings support closer follow-up of people with metabolic dysregulations for the diagnosis and prevention of psychiatric disorders.

Anxiety, depression, and stress-related disorders are common psychiatric disorders that affect approximately one-third of individuals during their life course. Increasing evidence suggests that biomarkers of lipid, apolipoprotein, and carbohydrate metabolism may be associated with the risk for anxiety, depression, and stress-related disorders, but results are inconsistent.

Against the above background, Charilaos Chourpiliadis, Karolinska Institutet, Stockholm, Sweden, and colleagues aimed to investigate whether the biomarkers of lipid, carbohydrate, and apolipoprotein metabolism are associated with the risk of anxiety, depression, and stress-related disorders.

For this purpose, the researchers conducted a population-based cohort study with longitudinal data collection that assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between 1985 and 1996, mainly in the Stockholm region in Sweden.

The main outcomes were the associations between biomarker levels and the risk of developing anxiety, depression, and stress-related disorders through the end of 2020. Nested case-control analyses were conducted within the cohort, including all cases of anxiety, depression, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by sex, year of birth, and year of enrollment to the AMORIS cohort, using incidence density sampling.

Population trajectories were used to illustrate the temporal trends in biomarker levels for controls and cases.

The study led to the following findings:

• 211 200 individuals (mean age at first biomarker measurement, 12.6 years; 58.0% male; 89.4% born in Sweden) participated in the study. During a mean follow-up of 21.0 years, a total of 16,256 individuals were diagnosed with depression, anxiety, or stress-related disorders.
• High levels of triglycerides (HR, 1.15) and glucose (hazard ratio [HR], 1.30) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88) were associated with a reduced risk. These results were similar for female and male participants and all tested disorders.
• The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the ten years preceding diagnosis, compared with control participants.

In conclusion, the researchers found elevated levels of triglycerides and glucose and reduced levels of HDL-C are linked to a higher risk of subsequent diagnosis of anxiety, depression, and stress-related disorders. The study provides further longitudinal evidence that metabolic syndrome or metabolic dysregulation raises the risk of developing common psychiatric disorders.

"These results add further evidence of the association between cardiometabolic health and psychiatric disorders and potentially advocate for a closer follow-up of individuals with metabolic dysregulations for prevention and early diagnosis of psychiatric disorders," the researchers wrote.

"There is a need for additional studies to explore whether rigorous or earlier interventions for cardiometabolic diseases could counteract such an association," they concluded.

Reference:

Chourpiliadis C, Zeng Y, Lovik A, et al. Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders. JAMA Netw Open. 2024;7(4):e244525. doi:10.1001/jamanetworkopen.2024.4525