Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Dr. Katie Watson
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.