The association between carotid atherosclerosis and treatment with lithium and antipsychotics in patients with bipolar disorder

Hsiao

Chiang

et al. 2021

Aust N Z J Psychiatry

Self Cite

Objective: Over a half century, lithium has been used as the first-line medication to treat bipolar disorder. Emerging clinical and laboratory studies suggest that lithium may exhibit cardioprotective effects in addition to neuroprotective actions. Fractalkine (CX3CL1) is a unique chemokine associated with the pathogenesis of mood disorders and cardiovascular diseases. Herein we aimed to ascertain whether lithium treatment is associated with favorable cardiac structure and function in relation to the reduced CX3CL1 among patients with bipolar disorder. Methods: We recruited 100 euthymic patients with bipolar I disorder aged over 20 years to undergo echocardiographic study and measurement of plasma CX3CL1. Associations between lithium treatment, cardiac structure and function and peripheral CX3CL1 were analyzed according to the cardiovascular risk. The high cardiovascular risk was defined as (1) age ⩾ 45 years in men or ⩾ 55 years in women or (2) presence of concurrent cardiometabolic diseases. Results: In the high cardiovascular risk group ( n = 61), patients who received lithium as the maintenance treatment had significantly lower mean values of left ventricular internal diameters at end-diastole (Cohen’s d = 0.65, p = 0.001) and end-systole (Cohen’s d = 0.60, p = 0.004), higher mean values of mitral valve E/A ratio (Cohen’s d = 0.51, p = 0.019) and superior performance of global longitudinal strain (Cohen’s d = 0.51, p = 0.037) than those without lithium treatment. In addition, mean plasma levels of CX3CL1 in the high cardiovascular risk group were significantly lower among patients with lithium therapy compared with those without lithium treatment ( p = 0.029). Multiple regression models showed that the association between lithium treatment and mitral value E/A ratio was contributed by CX3CL1. Conclusion: Data from this largest sample size study of the association between lithium treatment and echocardiographic measures suggest that lithium may protect cardiac structure and function in patients with bipolar disorder. Reduction of CX3CL1 may mediate the cardioprotective effects of lithium.

Section: Clinical Variablesmentioning

confidence: 99%

Cardioprotective potential of lithium and role of fractalkine in euthymic patients with bipolar disorder

Hsiao

Chiang

et al. 2021

Aust N Z J Psychiatry

Self Cite

“…For instance, clinical studies have revealed that lithium treatment reduces the risk of cardiovascular disease in patients with bipolar disorder. 26,34,35 In addition, laboratory studies have indicated that lithium administered at therapeutic levels ameliorates pathological hypertrophy and cardiac fibrogenesis in cellular and rat models of myocardial infarction. 6,36 Lithium likely achieves cardioprotective effects by inhibiting inflammatory responses, reactive oxidative stress, and endothelial dysfunction 37,38 and involves numerous signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Mood stabilizers and risk of all‐cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study

Tsai

et al. 2022

Acta Psychiatr Scand

Self Cite

Objectives People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all‐cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. Methods In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time‐dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. Results The SMRs of all‐cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all‐cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5‐year follow‐up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all‐cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). Conclusion In addition to having protective effects against suicide and all‐cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality.

“…AS has been recognized as a momentous pathological basis for cardiovascular diseases. The pathogenesis of AS is incredibly complex and has not yet been fully elucidated [ 1 , 3 ]. The biological behaviors of VSMCs exert important effects on the pathogenesis and development of AS.…”

Section: Discussionmentioning

confidence: 99%

“…With the acceleration of aging process in human society, the incidence rate of AS has been increasing year by year [ 2 ]. Besides, AS is the major contributor to death of cardiovascular disease worldwide, and also one of the main causes of acute cardiovascular disease [ 3 ]. This phenomenon has been widely concerned by the cardiovascular community.…”

Section: Introductionmentioning

confidence: 99%

Cullin3 (CUL3) suppresses proliferation, migration and phenotypic transformation of PDGF-BB-stimulated vascular smooth muscle cells and mitigates inflammatory response by repressing Hedgehog signaling pathway

Xiang

Xia

et al. 2021

Bioengineered

Vascular smooth muscle cell (VSMC) hyperplasia is closely associated with AS progression. Hence, it is of great significance to elucidate the molecular mechanisms underlying the involvement of VSMCs in AS. SHH antagonist can inhibit the excessive proliferation, migration and phenotypic transformation of PDGF-BB-induced VSMCs. It has been proved that CUL3 can suppress Hedgehog signaling. This current work was designed to identify the biological role of CUL3 in the behaviors of VSMCs in AS and investigate the potential molecular mechanism. VSMCs were treated with PDGF-BB to establish the cell model in vitro . Levels of CUL3, SHH and Gli1 in PDGF-BB-stimulated VSMCs were measured by RT-qPCR analysis. Then, the precise functions of CUL3 in VSMCs were determined from the perspectives of proliferation, migration, apoptosis and phenotype transformation. Besides, the influence of CUL3 on inflammatory response in VSMCs was evaluated. Moreover, the impact of CUL3 on Hedgehog signaling pathway was also investigated. In the present research, it was observed that CUL3 was lowly expressed and SHH and Gli1 were highly expressed in PDGF-BB-stimulated VSMCs. Upregulation of CUL3 suppressed the excessive proliferation, migration and phenotypic transformation and facilitated the apoptosis of PDGF-BB-stimulated VSMCs. In addition, elevation of CUL3 alleviated inflammatory response in PDGF-BB-stimulated VSMCs. Importantly, CUL3 overexpression inactivated Hedgehog signaling pathway. To conclude, CUL3 might regulate the biological behaviors of VSMCs in AS by modulating Hedgehog signaling pathway. These data encourage to further investigate any potential therapeutic role of CUL3 in animal models of AS and explore therapeutic values for AS clinically.