Inflammation associated with left ventricular hypertrophy in bipolar disorder: A cross-sectional study.

OBJECTIVE: Inflammation has received increasing attention as a contributor to the pathophysiology of bipolar disorder (BD) and cardiac hypertrophy into heart failure (HF). Accordingly, we chose BD-related inflammatory markers to investigate their relationships with cardiac left ventricular function and structure in BD. METHODS: Sixty physically healthy and euthymic patients with bipolar I disorder were recruited to compare with 50 healthy normal controls. The echocardiography was performed to estimate left ventricular mass index (LVMI) as a parameter of LV hypertrophy (LVH) and left ventricle ejection fraction (LVEF) as a parameter of systolic function. An LVEF above the normal range (>70%) was defined as a hyperdynamic heart. Participants' levels of inflammatory and atherosclerosis-related parameters were measured. RESULTS: Compared with normal controls, BD group had significantly higher rates of LVH (63% vs. 42%) and hyperdynamic heart (32% vs. 2%) and higher mean values of LVMI and LVEF. After adjustment for the effects of BMI and age, multiple regression analyses of BD group showed that the peripheral level of interleukin-8 was positively associated with LVMI and the level of soluble tumor necrosis factor receptor 1 (sTNF-R1) was positively associated with LVEF. CONCLUSIONS: Patients with BD from young adulthood are likely to have LVH with normal LV function and hyperdynamic heart associated with diastolic dysfunction. Low-grade inflammation may underlie the mechanisms of LV hypertrophy and cardiac dysfunction in BD patients.

Lithium exposure and chronic inflammation with activated macrophages and monocytes associated with atherosclerosis in bipolar disorder.

BACKGROUND: Atherosclerosis accounts for cardiovascular diseases (CVDs). This study aimed to explore the association between carotid intima-media thickness (CIMT), psycho-pharmacotherapy, and inflammatory markers along with other molecules related to atherosclerosis in bipolar disorder (BD). METHODS: The euthymic patients with bipolar I disorder (BD-I) aged over 20 years were recruited to measure CIMT through ultrasound and the blood levels of lipid profiles, soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R), monocyte chemoattractant protein-1, chitinase 3-like 1, endothelial adhesive proteins, and thrombin-antithrombin complex. RESULTS: Participants were 103 BD-I patients with mean 44.3 years old. The ratio of lithium exposure in relation to illness chronicity and the current daily dosage of lithium therapy exhibited an inverse relationship with CIMT in the entire sample. After controlling for age and BMI, multivariate regression indicated that a higher lithium level was significantly associated with decreased CIMT in the entire sample, high-risk (those with CVDs or endocrine diseases, N = 48), middle-risk (those without CVDs and endocrine diseases, N = 55), and low-risk (those aged <45 years in the middle-risk subgroup, N = 43) subgroups. Furthermore, higher levels of sTNF-R1 in the entire sample and high-risk subgroup and sIL-6R in the middle- and low-risk subgroups were statistically associated with greater CIMT. LIMITATION: The age range was too wide to control for the effect of age on CIMT and medication. CONCLUSIONS: Lithium exposure may be a protective factor for atherosclerosis progression in BD-I. The chronic inflammation in BD-I with activated macrophages and monocytes may link with the atherosclerosis development over time.

Peripheral inflammatory markers associated with brain volume reduction in patients with bipolar I disorder.

BACKGROUND: 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. METHODS: 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-1ß, and transforming growth factor-ß1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others. RESULTS: 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. CONCLUSIONS: 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.

Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia.

Obesity, aging, and pathophysiology of schizophrenia (SCZ) may collectively contribute to the gray matter loss in brain regions of SCZ. We attempted to examine the association between volumes of specific brain regions, body mass index (BMI), inflammatory markers, and clinical features in older SCZ patients. METHOD: Clinically stable outpatients with schizophrenia (DSM-IV) aged ≥50 years were recruited to undergo whole-brain magnetic resonance imaging. We measured patients' plasma levels of soluble tumor necrosis factor receptor-1, soluble interleukin (IL)-2 receptor (sIL-2R), IL-1ß, and IL-1 receptor antagonist (IL-1Ra). Clinical data were obtained from medical records and interviewing patients along with their reliable others. RESULTS: There were 32 patients with mean age 58.8 years in this study. Multivariate regression analysis found only higher BMI significantly associated with lower volume of total gray matter, bilateral orbitofrontal and prefrontal cortexes, and the right hippocampal and frontal cortexes. Increased intensity of residual symptoms (higher Positive and Negative Syndrome Scale scores) was related to lower volumes of frontal lobe, prefrontal cortex, insula, hippocampus, left hemisphere amygdala, and total white matter. The lower volume of left anterior cingulum was associated with older age and higher sIL-2R plasma level; and higher IL-1Ra level was associated with greater right anterior cingulate volume. Older age at illness onset was significantly associated with the smaller right insula volume. CONCLUSIONS: Higher BMI, more residual symptoms, and inflammatory activity in IL-2 and IL-1 systems may play a role in gray matter loss in various brain regions of schizophrenia across the life span.

Factors Predicting the Surgical Risk of Osteoporotic Vertebral Compression Fractures.

The aim of our study was to investigate the association between global spinal alignment, spinopelvic parameters, and outcomes of osteoporotic vertebral compression fractures (OVCF). Patients with vertebral compression fractures seen at our hospital between October 2017 and November of 2018 with a bone mineral density (BMD) T-score < -2.5 were recruited for the study. Surgical intervention was performed after eight weeks of conservative treatment depending on clinical symptoms and the willingness of patients. Spinopelvic and sagittal alignment parameters were compared between patients who had surgery and those that did not. Seventy-nine patients were included in the study. Twenty-five patients (31.6%, mean age: 73.28 ± 9.78 years) received surgery, and 54 (68.3%, mean age: 73 ± 8.58 years) conservative treatment only. Pelvic tilt, pelvic incidence, and local kyphotic angle were statistically different between the groups (all p < 0.05). A sagittal vertical axis ≥ 50 mm, distance between the C7 plumb line and the center of the fractured vertebra (DSVA) ≥ 60 mm, pelvic incidence outside of the range of 44 to 62°), and pelvic tilt ≥ 27° were associted with the need for surgical intervention. Measurement of spinopelvic parameters can predict the need for surgery in patients with OVCF.

Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) and aging appear to be associated with inflammatory activation. Inflammatory processes might affect hippocampal function, neurogenesis, and gray matter loss. This study investigated the relationship between BD-specific brain regions and the total gray matter volume, peripheral inflammatory markers, and clinical features in older patients with BD. METHODS: We recruited euthymic patients with bipolar I disorder aged ≥50 years to undergo whole-brain magnetic resonance imaging. Each brain region was divided by an individual's total intracranial volume to obtain that brain region's volume in percentage relative to the total intracranial volume. We measured the plasma levels of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin (IL)-2 receptor (sIL-2R), sIL-6R, IL-1ß, and IL-1 receptor antagonist when patients were euthymic. Clinical data were obtained by reviewing available medical records and interviewing patients along with their reliable others. RESULTS: There were 32 patients with a mean age of 61.2 ±â€¯8.3 years and a mean age at illness onset of 33.4 ±â€¯13.8 years in this study. Stepwise regression showed that the right hippocampal volume was negatively associated with the levels of sIL-2R and sTNF-R1. The left hippocampal volume were negatively associated with the sIL-2R level and body mass index. The total gray matter volume had an inverse relationship with sTNF-R1 and IL-1ß levels. The duration of bipolar illness, lithium treatment, and antipsychotic use were not associated with hippocampal and total gray matter volumes. CONCLUSIONS: It is suggested that persistent inflammation is associated with reduction of hippocampal and gray matter volumes in older patients with BD. This phenomenon is supported by increases in sTNF-R1, sIL-2R, and IL-1ß levels. Neuroinflammation due to aging, obesity, and BD pathophysiology may play a role in BD neuroprogression across the life span.