Vascular Mortality in Participants of a Bipolar Genomics Study

Fiedorowicz, Jess G.; Jancic, Dubravka; Potash, James B.; Butcher, Brandon; Coryell, William

doi:10.1016/j.psym.2014.02.001

Cited by 20 publications

(11 citation statements)

References 21 publications

(24 reference statements)

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“…Several papers have reported higher levels of proinflammatory cytokines in those with bipolar I disorder during euthymic states (Barbosa et al, 2013a; do Prado et al, 2013; Modabbernia et al, 2013) and assessment of the duration of euthymia in future work may potentially add clarity to divergent findings. State-related inflammation changes may also explain the observed dose response between the persistence of mood symptoms, cardiovascular mortality and vascular dysfunction (Fiedorowicz, 2014; Fiedorowicz et al, 2012; Fiedorowicz et al, 2014; Fiedorowicz et al, 2009; Sodhi et al, 2012). …”

Section: Resultsmentioning

confidence: 99%

Peripheral inflammation during abnormal mood states in bipolar I disorder

Fiedorowicz

Prossin

Johnson

et al. 2015

Journal of Affective Disorders

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Background Bipolar disorder carries a substantive morbidity and mortality burden, particularly related to cardiovascular disease. Abnormalities in peripheral inflammatory markers, which have been commonly reported in case-control studies, potentially link these co-morbidities. However, it is not clear whether inflammatory markers change episodically in response to mood states or are indicative of chronic pro-inflammatory activity, regardless of mood, in bipolar disorder. Methods Investigations focused on comparing concentrations of specific inflammatory cytokines associated with immune activation status (primary outcome = tumor necrosis factor alpha (TNF-α)) in 37 participants with bipolar disorder across 3 mood states (mania N=15, depression N=9, normal mood N=13) and 29 controls without a psychiatric disorder (total N=66). Cytokine levels were also compared to T1ρ, a potential neuroimaging marker for inflammation, in select brain regions in a subsample (N=39). Results Participants with bipolar disorder and healthy controls did not differ significantly in inflammatory cytokine concentrations. However, compared to cases with normal mood, cases with abnormal mood states (mania and depression) had significantly elevated levels of TNF-α, its soluble receptors (sTNFR1/sTNFR2), other macrophage-derived cytokines (interleukin 1β (IL-1β), IL-6, IL-10, IL-18) in addition to IL-4, interferon-γ, monocyte chemotactic protein-1, fibroblast growth factor β, and vascular endothelial growth factor. Cytokine levels were not correlated with signals from T1ρ imaging in selected structures (amygdalae, hippocampi, hypothalamus, anterior cingulate gyrus, middle frontal gyrus). Limitations Participants were not followed prospectively across mood states. Conclusion Activation of inflammatory markers was found in abnormal mood states of bipolar disorder. Longitudinal study of individuals with mood disorders is needed to confirm these findings and to elucidate the time course of any such changes.

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Section: Resultsmentioning

confidence: 99%

Peripheral inflammation during abnormal mood states in bipolar I disorder

Fiedorowicz

Prossin

Johnson

et al. 2015

Journal of Affective Disorders

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“…Such physiological effects could explain the dose-response between depressive symptom burden and vascular outcomes [22, 23]. The neurobiological underpinnings of depression may most plausibly mediate any such vascular effects through alterations in the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and inflammation.…”

Section: Discussionmentioning

confidence: 99%

The development of depressive symptoms during medical internship stress predicts worsening vascular function

Fiedorowicz¹,

Ellingrod²,

Kaplan³

et al. 2015

Journal of Psychosomatic Research

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Objective We sought to prospectively determine whether the onset of internship stress and any subsequent depression alters physiological markers of early vascular disease Methods We explored potential mechanisms linking stress and depression to vascular disease in a prospective cohort of 37 participants exposed to medical internship stress, an established precipitant of depressive symptomatology. Results Change in depressive symptom score from baseline over one year of internship stress was inversely correlated with change in the reactive hyperemia index (RHI), a measure of peripheral endothelial function (r=0.41, p=0.01). The change in depressive symptoms in the first six months of internship was similarly related to change in RHI over one year (r=0.38, p=0.02). While the development of depressive symptoms did not significantly impact changes in endothelial progenitor cells (EPCs), EPCs did significantly decrease with the year of internship stress (11.9 to 3.4 cells/ml blood; p=0.01). Conclusion Endothelial function may be a critical link between stress, depression, and cardiovascular disease and a feasible surrogate outcome for prospective studies.

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“…In a study of 435 participants with bipolar disorder followed prospectively for up to 25 years, the longitudinal burden of clinically significant manic or hypomanic symptoms was significantly associated with vascular mortality [15]. In a 7-year mortality follow-up of 1716 persons with bipolar disorder, a measure of depressive symptom burden, the duration of the most severe depression, predicated vascular mortality [16]. Taken together, these findings suggest that the risk of vascular mortality with mood disorders is related to the amount of time one is symptomatic.…”

Section: Course Of Illness and Riskmentioning

confidence: 99%

Depression and Cardiovascular Disease: An Update on How Course of Illness May Influence Risk

Fiedorowicz

2014

Curr Psychiatry Rep

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Depression constitutes a novel and independent risk factor for cardiovascular disease, which despite extensive support in the literature has been underappreciated. While much of the evidence for depression as a risk factor for cardiovascular disease is based on studies following myocardial infarction, the elevated vascular risk conveyed by depression is not confined to periods following acute coronary syndromes. For that matter, the risk appears across mood disorders with evidence for even greater risk in bipolar disorder. This review summarizes the literature linking depressive disorders to cardiovascular mortality with a focus on how the course of illness of mood disorders may influence this risk. Mood disorders may influence risk over decades of illness in a dose-response to symptom burden, or the persistence of affective symptomatology. This may be mediated through changes in the activity of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis, and inflammatory cytokines. Whether treatment of depression can mitigate this risk is not established although there are suggestions to support this contention, which could be better studied with more effective treatments of depression and larger standardized samples. Directions for future study of mechanisms and treatment are discussed. Regardless of causal mechanisms, persons with depressive disorders and other risk factors for vascular disease represent a neglected, high-risk group for cardiovascular events. In addition to the appropriate treatment for depression, screening and optimized management of traditional risk factors for cardiovascular diseases is necessary.

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Vascular Mortality in Participants of a Bipolar Genomics Study

Cited by 20 publications

References 21 publications

Peripheral inflammation during abnormal mood states in bipolar I disorder

Peripheral inflammation during abnormal mood states in bipolar I disorder

The development of depressive symptoms during medical internship stress predicts worsening vascular function

Depression and Cardiovascular Disease: An Update on How Course of Illness May Influence Risk

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