Serum 4-Hydroxynonenal Linked to Depression in Coronary Artery Disease

blood tests
blood tests
Investigators examined the relationship between lipid peroxidation markers and depression in patients with coronary artery disease.

For patients with coronary artery disease, 4-hydroxynonenal may be an important marker of depression and may be involved in the progression of the depressive disorder, according to a study published in Psychiatry Research.

Assuming oxidative stress as a possible mechanism underlying depression, researchers in the current study examined the relationship between depression and markers of early lipid peroxidation, measured by lipid hydroperoxides and lipid-polymer hybrid (LPH), and late lipid peroxidation, measured by 4-hydroxynonenal and 8-isoprotane. Serum levels of lipid peroxidation markers were measured in patients with coronary artery disease (N=120) undergoing cardiac rehabilitation at the UHN Toronto Rehabilitation Institute from 2012 to 2015. Investigators used the Structured Clinical Interview for DSM Axis I Disorders- Depression Module (SCID) to diagnose baseline levels of depression, and they calculated the severity of depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D).

The researchers used multivariate mixed models to compare the trajectories of serum 4-hydroxynonenal, LPH, and 8-isoprotane between participants with and without depression who were undergoing 6 months of cardiac rehabilitation. Similar models were used to evaluate the associations between CES-D scores and serum 4-hydroxynonenal, LPH, and 8-isoprotane over the 6-month rehabilitation. Participants with depression (n=18) showed significantly higher serum 4-hydroxynonenal concentrations than participants without depression (n=102) at baseline, but no significant between-group difference was seen in serum LPH or 8-isoprotane. Furthermore, participants without depression showed a greater decrease in serum 4-hydroxynonenal than participants with depression. Increases in 4-hydoxynonenal serum concentrations over the course of 6 months were significantly associated with increased depression severity, as measured by decreases in CES-D scores during that same time period.

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Study investigators conclude that these findings indicate that 4-hydoxynonenal may play a significant role in depression development and progression and could be an important marker of depression for patients with coronary artery disease. They note that “[f]uture studies should emphasize assessment of the oxidative balance by including markers of exogenous and endogenous antioxidants as well as a greater number of depressed patients.”


Rosen M, Chan P, Saleem M, et al. Longitudinal associations between 4-hydroxynonenal and depression in coronary artery disease patientsPsychiatry Res. 2018; 270:219-224.