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Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients.
Euthymic patients with bipolar I disorder (BD-I) aged 20–45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others.
We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes.
The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.
Atherosclerosis can result in serious cardiovascular disease (CVD) and is associated with inflammation and psychopharmacological treatment in bipolar disorder. We attempt to investigate the effects of lithium and inflammation on the atherosclerotic development in older bipolar adults at high risk for cardiovascular disease.
The euthymic out-patients with bipolar I disorder aged over 45 years and concurrent endocrine or cardiovascular disease were recruited to measure their bilateral carotid intima media thickness (CIMT) and circulating levels of lithium, valproate, sTNF-R1, sIL-6R, and lipid profile. All clinical information were obtained by directly interviewing patients and reviewing all medical records.
Forty eight patients with mean 48.3 years old and mean 27.2 years of age at illness onset were recruited. After controlling for the body mass index, multivariate regression analyses showed that older age, lower lithium level, and higher plasma sTNF-R1 level were associated with higher CIMT and collectively accounting for 33.1% of the variance in CIMT. Blood level of low density lipid or valproate has none relationship with CIMT.
Lithium treatment may protect older bipolar patient, even those at high risk for CVD, from atherosclerotic development. Furthermore, persistent inflammatory activation, particularly macrophage activation, may be associated with the accelerating development of atherosclerosis.
Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity.
Using data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case–control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities.
Suicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls.
Patients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction.
Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.
In this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder.
Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case–crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder.
Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke.
Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.
Declaration of interest
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