Insulin resistance ( IR) is a physiological state characterized by the attenuated response of peripheral receptors to insulin. It is a known risk factor for somatic and brain disorders, including cardiovascular disease, Alzheimer’s disease, and major depressive disorder (MDD).
Several plausible mechanisms link IR to major depressive disorder (MDD). Insulin resistance leads to decreased insulin-mediated glucose disposal, compensatory hyperinsulinemia, and type 2 diabetes.
Characterizing these associations represents a critical step toward better phenotyping , a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD. We investigated whether IR was positively associated with the presence of major depression, the severity of major depression, and the chronicity of major depression using the Netherlands Study of Depression and Anxiety (NESDA).
Methods
The NESDA study is a Dutch longitudinal study of adults that describes the course and consequences of depressive and anxiety disorders. We studied 1269 participants with proteomic data in 3 diagnostic groups:
- Current TDM.
- TDM referred.
- Those without a history of the disorder (control group).
Non-Dutch speakers and those with a history of other psychiatric disorders were excluded . The NESDA protocol was approved by the ethical committee of Vrije University Medical Center and all participants provided written informed consent.
We used 2 well-validated surrogate biomarkers of IR , the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglyceride to high-density lipoprotein (HDL) ratio, with the goal of understanding whether the use of different measures of IR substitutes has consistent associations with MDD.
Those in the bottom quartile of QUICKI were categorized as insulin resistant and all others as insulin sensitive , as is standard in IR studies.
The triglyceride-HDL ratio is an index based on measurements from fasting blood samples and a sex-specific cut-off point for IR was used. .
Trained research staff assessed depression diagnostic status using the Composite International Diagnostic Interview, version 2. The Depressive Symptomatology Inventory assessed depression severity. Chronicity of depression during the previous 4 years was measured using the life chart interview.
The association between depression group and IR status was assessed using multivariable-adjusted multinomial logistic regression. We used adjusted linear regression to investigate the association between IR and depression characteristics among current and referred cases.
A complementary analysis adjusted the models of MDD characteristics for antidepressant use. All models were adjusted for age, sex, education, relationship status, smoking, and alcohol consumption.
Results
Participants in the RI group (defined by QUICKI) were older, less educated, and had a higher body mass index than those who were insulin sensitive.
Insulin resistance was associated with current MDD compared with control individuals (odds ratio [OR], 1.51; 95% CI, 1.08-2.12), but not with MDD. referred (OR, 1.14; 95% CI, 0.79-1.64).
Among participants with current MDD, both measures of IR were positively associated with depression severity .
The chronicity of depression was associated with the triglyceride-HDL ratio but not with the QUICKI.
Among participants with remitted MDD, neither severity nor chronicity of depression was associated with IR. There were no substantial changes in model results after adjustment for antidepressant use.
Linear Regression Models of the Association Between Depression Characteristics and Measures of Insulin Resistance: Depression Severity and Depression Chronicity Among Participants with Current MDD
Discussion
We report an association between insulin resistance (IR) and current major depressive disorder (MDD), but not with remitted MDD, suggesting that IR is a state , rather than a trait, biomarker of depression.
Among IR-specific biomarkers, triglyceride-HDL ratio was positively associated with depression severity and chronicity (again, only among participants with current MDD), while IR measured by QUICKI was associated with depression severity. the Depression.
Together, these biomarkers of metabolic dysfunction represent simple and clinically accessible methods of identifying IR among currently depressed patients.
A limitation of this analysis was the cross-sectional design. Longitudinal analyzes need to extend these findings and examine temporality and are the subject of our current investigations.
