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.