Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders

Abstract

ImportanceBiomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent.ObjectiveTo examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders.Design, Setting, and ParticipantsThis population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023.ExposuresLipid, apolipoprotein, and carbohydrate biomarkers measured in blood.Main Outcomes and MeasuresThe associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, 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 cases and controls.ResultsA total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for 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 10 years preceding diagnosis, compared with control participants.Conclusions and RelevanceIn this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio(NHHR) with depressive symptoms: recent findings from NHANES 2005– 2018

“…It's worth noting that the frequency of adult depression in the U.S. is increasing each year, affecting about 8% of adults in the U.S., and is higher in women than in men (4) .A high incidence, a high clinical cure rate but a low treatment acceptance rate and a high relapse rate are the hallmarks of depression as a mental illness. Along with cognitive abnormalities that could interfere with day-to-day learning and work, the patient may also experience hallucinations and, in extreme circumstances, suicidal thoughts (5,6).Depressed moods may cause immune, endocrine and neurological dysfunction in the body, which can increase susceptibility to disease and lead to death (7) .According to a recent meta-analysis, depression raised the probability of dying by 50% (8).However, current treatment regimens remain inadequate for some patients, and some may experience intolerable side effects, making the discovery of new depression-related bioindicators crucial for the prevention and treatment of depression.Many studies have shown that the pathogenesis of depression is closely associated with in ammation, neuroimmune dysfunction, and abnormalities in lipid metabolism (9)(10)(11)(12) .Previous ndings on the association of biomarkers in lipid metabolism with depression have however been controversial, with some studies reporting that Triglycerides (TG) have a positive correlation with the likelihood of developing depression, while low-density lipoproteins (LDL-C), total cholesterol (TC), and high-density lipoproteins (HDL-C) have a negative correlation (13)(14)(15)(16) , In contrast, Raised HDL-C levels were substantially positively correlated with depression in both sexes, according to a cross-sectional study (17) .Jane E. Persons et al concluded from a meta-analysis that there was a U-shaped relationship between LDL and depression when LDL was used as a continuous variable (18) .Non-HDL-C mainly contains cholesterol from all atherogenic lipoprotein particles, apolipoproteins, very low-density lipoprotein cholesterol (VLDL-C), and IDL-C, and relevant studies have demonstrated that the major components contained within non-HDL-C are linked to an increased risk of suffering from depression (19) . Therefore, the development of newer and more reliable lipid parameters is necessary for the prediction and management strategies of depression.…”