Mood Disorders and Cardiovascular Disease: Focusing on Early Prevention

Major depressive disorder (MDD) and bipolar disorder (BD) are common mood disorders among adolescents in the US. BD involves episodes of mania/hypomania (elevated mood) that can alternate with depression episodes. MDD involves episodes of depression (sadness, lack of interest or pleasure in daily activities) lasting at least two weeks. MDD and BD can be severe and potentially disabling conditions. Adolescent onset of mood disorders is associated with chronicity of disorder into adulthood and comorbidity with other disorders.

In this issue of Circulation, Goldstein et al summarize the existing evidence documenting an association between MDD and BP and accelerated atherosclerosis and early cardiovascular disease (CVD) in youth.¹ Based on the current evidence the writing group proposes MDD and BD to be included as tier II moderate-risk conditions that require risk stratification and management in accordance with Expert Panel recommendations.

Our current knowledge warrants the inclusion of MDD and BD as moderate-risk conditions for early CVD. As Goldstein et al describe, diagnosis of clinical depression has been prospectively associated with increased ischemic heart disease mortality in the National Health and Nutrition Examination Survey III, independent of psychiatric medications.² Depressive symptoms have also been associated with carotid artery intima-media thickness (CIMT) and endothelial dysfunction in youth. In addition, cardiovascular risk factors, obesity, Type 2 diabetes mellitus, and dyslipidemia have all been noted to be higher among adolescents and young adults with MDD and BD. Potential mechanisms behind the mood disorder and CVD associations include behavioral factors as well as pathophysiological processes. Extensive evidence exists for the relationship between inflammation, oxidative stress, and autonomic system dysfunction and MDD and BD among adults. As Goldstein et al note, the limited evidence among youth is concordant with findings among adults, for example a few small studies have noted an association between depressive symptoms and BD and elevated inflammatory markers. Smoking, tobacco use, sleep disturbances, and a sedentary lifestyle are also associated with both mood disorders and CVD, yet in studies conducted to date behavioral factors do not fully account for the relationship between mood disorders and CVD.

Unfortunately, most adolescents in the US are not treated for their mood disorders. Evidence for the relationship between mood disorders and CVD comes from largely untreated populations. Little if any evidence exists of the potential benefit for CVD risk that treatment for mood disorders may convey. Conversely, treatment, in particular with psychiatric medications, may increase cardiometabolic factors such as weight gain. As the writing group describes, the potential for a bidirectional role of mood disorders and CVD is plausible, particularly considering the impact of psychiatric medications on traditional CVD risk factors. However no work to date has examined the association between psychiatric medications and CVD or CVD mortality among youth. Future work should focus on the role of treatment, with or without psychiatric medications, for MDD and BD and on the effects that treatment may have on CVD and CVD risk factors.

Sex differences in the relationship between mood disorders and CVD have been noted in some studies and deserve further examination. Findings are mixed; some studies note a relationship between mood disorders and CVD among women while others have noted an association only among men. Differential behavioral responses or physiological mechanisms may contribute to potential sex differences. Furthermore there are noted differences in the prevalence of mood disorders by sex, with young women having nearly a two-fold higher prevalence of depression compared to young men.³ Understanding sex differences in the relationship between mood disorders and CVD could prove fruitful in devising treatment strategies and interventions. Likewise, while not extensively, racial/ethnic differences in the relationship between mood disorders and CVD have also been documented and may contribute to the noted racial/ethnic disparities in CVD. For example, among adults depressive symptoms have been associated with CVD mortality among blacks but not whites. Blacks and Hispanic adults report more severe and untreated MDD than their white counterparts, potentially placing them at greater risk of CVD.^4,5 Among adolescents, Hispanics have an increased prevalence of depression compared to their white counterparts.³ Differential racial/ethnic effects of mood disorders on CVD should be further examined, particularly as they aid in the understanding of pathways that may confer elevated risk differentially by racial/ethnic group.

The recommendation by Goldstein et al to include MDD and BD as tier II moderate-risk conditions for early CVD in youth is merited. Childhood and adolescence are particularly important periods of development. The prevention of CVD and CVD mortality in adulthood hinges on the early prevention of CVD risk factors and the effective management of conditions, such as mood disorders, that accelerate the development of CVD in youth.