Open Access Peer-Reviewed



Coronary calcium score as an expression of multisystemic progression of bipolar disorder

Elisa Brietzke1,2, Rodrigo B. Mansur1, Roger S. McIntyre1,3

We read with interest the study by Wageck et al.1 recently published in Revista Brasileira de Psiquiatria. In their analysis, the authors describe a positive association between number of hospitalizations and coronary calcium score (CCS), a well-defined predictor of cardiovascular mortality in the general population, in individuals with bipolar disorder (BD). In the Discussion, the authors hypothesize that the activation of inflammatory response which is associated with mood episodes, especially more severe episodes (i.e., those requiring hospitalization), may be a causal explanation for the premature onset or progression of atherosclerotic pathology, although inflammatory status was not assessed in the study. While the results of this study still need to be replicated, they provide novel insights into the systemic pathophysiology associated with severe and recurrent mood disorders. In addition to being neuro-progressive illnesses,2 mood disorders are perhaps more comprehensively conceptualized as conditions of multi-systemic progression.3 In accordance with this view, multi-systemic progression would be mediated by persistent inflammatory activation, insulin resistance, and oxidative stress.4,5 Within this framework, cardiovascular disease seems to be a final common endpoint of the alterations and effector systems mentioned earlier.

Alternatively, it could be hypothesized that the marked systemic alterations which lead to a high CCS score are causally associated with a more severe neuroprogression. This comports with a robust body of evidence from both animal studies and clinical trials which provides the basis for repurposing pharmacological agents that primarily target the metabolic system, such as anti-inflammatory or antidiabetic agents (e.g., intranasal insulin, GLP-1 agonists), to reduce symptoms or modify the course of mood disorders. Indeed, our group has proposed the term ''meta-boptosis'' to refer to the myriad changes in energy balance of peripheral origin with central nervous system (CNS) penetration, causing apoptosis and changes in the substrates subserving neuroprogression and a less favorable clinical course in BD.

From a practical point of view, the findings of Wageck et al.1 also highlight the need to reinforce cardiovascular assessment and care in individuals with mood disorders, especially in long-term and severe presentations of these psychiatric conditions. In addition, they shed light on the need for a holistic approach to individuals with mood disorders, blurring the limits between psychiatry and general medicine to provide evidence-based and integrated care.


The authors report no conflicts of interest.


1. Wageck AR, Torres FS, Gama CS, Martins DS, Scotton E, Reckziegel R, et al. Cardiovascular risk and bipolar disorder: factors associated with a positive coronary calcium score in patients with bipolar disorder type 1. Rev Bras Psiquiatr. 2018;40:163-8.

2. Passos IC, Mwangi B, Vieta E, Berk M, Kapczinski F. Areas of controversy in neuroprogression in bipolar disorder. Acta Psychiatr Scand. 2016;134:91-103.

3. Czepielewski L, Daruy Filho L, Brietzke E, Grassi-Oliveira R. Bipolar disorder and metabolic syndrome: a systematic review. Rev Bras Psiquiatr. 2013;35:88-93.

4. Rosenblat JD, Brietzke E, Mansur RB, Maruschak NA, Lee Y, McIntyre RS. Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: Evidence, pathophysiology and treatment implications. J Affect Disord. 2015;188:149-59.

5. Brietzke E, Kapczinski F, Grassi-Oliveira R, Grande I, Vieta E, McIntyre RS. Insulin dysfunction and allostatic load in bipolar disorder. Expert Rev Neurother. 2011;11:1017-28.

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