Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.

Prevalence and 3-year incidence of physical illnesses after schizophrenia diagnosis: Comparison with general population.

AIM: People with schizophrenia are at a greater risk of poor physical health than the general population. This study investigated the annual incidence of physical illnesses after a new schizophrenia diagnosis, which has rarely been investigated in the literature. METHODS: The authors collected data from Taiwan's National Health Insurance Research Database from January 1, 1996, to December 31, 2013, and enrolled 1910 patients with newly diagnosed schizophrenia cases aged 10-40 years and 7640 age- and sex-matched controls from the general population. They estimated the 1-year prevalence and annual incidence rate ratio (IRR) of specified physical diseases across 3 years in the schizophrenia group compared with the controls. RESULTS: Several physical illnesses were prevalent within 1 year of schizophrenia diagnosis. Regarding incident physical illnesses, patients had a moderate to strong risk of numerous physical illnesses (IRR > 3.0: ischemic heart disease, cerebrovascular disease, diabetes mellitus, and cancer; IRR 1.8-3.0: other forms of heart disease, vein and lymphatic diseases, pneumonia, chronic hepatic disease, and ulcer disease) within the first year after schizophrenia diagnosis. The IRRs of most physical illnesses declined over 3 years, except for that of cerebrovascular disease, which significantly increased (IRR > 3.0) over the 3 years after schizophrenia diagnosis. Cerebrovascular disease had a significant incidence risk (IRR > 3) persistently across the 3 years. CONCLUSION: Various comorbid physical illnesses can occur in the early stages of schizophrenia. Clinicians should consider these vulnerabilities to physical illnesses during the evaluation of patients with newly diagnosed schizophrenia by attempting to prevent, screen for, and manage them.

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.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

Healthcare utilization and comorbidity shortly before suicide mortality in patients with attention-deficit/hyperactivity disorder: a nested case-control study.

BACKGROUND: Few studies have analyzed healthcare utilization before suicide among individuals with attention-deficit/hyperactivity disorder (ADHD). This study examined the pattern of healthcare utilization and comorbidities shortly before death among patients with ADHD who died by suicide and compared these data with those of living controls. This study used Taiwan's National Health Insurance Research Database to identify patients with ADHD (N = 379,440) between January 1, 2001, and December 31, 2016. Subsequently, the researchers identified 159 suicide decedents by linking each patient with the National Mortality Database. By conducting a nested case-control study with risk-set sampling from the ADHD cohort, the researchers selected 20 age- and sex-matched controls (n = 3180) for each patient who died by suicide (cases). The researchers then applied conditional logistic regression to investigate differences in healthcare utilization as well as psychiatric and physical comorbidities between case patients and controls. Case patients had higher healthcare utilization within 3 months before suicide, particularly in the psychiatry, emergency, internal medicine, neurosurgery, and plastic surgery departments. These patients also had higher risks of psychiatric comorbidities, including schizophrenia, bipolar disorder, depressive disorder, and sleep disorder, as well as physical comorbidities such as hypertension and other forms of heart disease. Among patients with ADHD, suicide decedents had increased healthcare utilization and higher risks of specific psychiatric and physical comorbidities than living controls. Thus, for suicide prevention among individuals with ADHD, suicide risk must be detected early and comorbidities should be adequately managed.

Healthcare utilization, psychiatric disorders, and physical illnesses shortly before suicide mortality in adolescents in Taiwan.

BACKGROUND: This study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls. METHODS: From Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10-19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case-control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls. CONCLUSIONS: The findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population.

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.

Call to action regarding the vascular-bipolar link: A report from the Vascular Task Force of the International Society for Bipolar Disorders.

OBJECTIVES: The association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular-bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment. METHODS: An international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps. RESULTS: The association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular-bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets. CONCLUSIONS: Further research focused on the vascular-bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder.

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.

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.

Excess incidence and risk factors for recurrent pneumonia in bipolar disorder.

AIM: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. METHODS: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. RESULTS: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. CONCLUSION: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

BACKGROUND: The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. METHODS: Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. RESULTS: Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). CONCLUSIONS: Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

Psychological Outcomes and Medical Morbidity of Patients With Bipolar Disorder and Co-Occurring Alcohol Use Disorder.

OBJECTIVE: Patients with bipolar disorder are at a high risk for comorbid alcohol use disorder, and both disorders are associated with poor outcomes and multiple morbidities. This study aimed to explore not only the psychosocial functioning and psychopathological outcomes but also the medical morbidity of patients with bipolar disorder with and without alcohol use disorder. METHODS: Outpatients with bipolar I disorder (DSM-IV) were recruited from a psychiatric teaching hospital in Taiwan (N = 393). Data on psychiatric symptoms, psychosocial functioning, and physical health were obtained through interviews with patients and collaterals, patient self-report, and medical record reviews. RESULTS: Participants had a mean age of 41.1 years (SD = 11.9) and were mostly female (n = 255, 64.9%). Fewer than 10% (n = 34, 8.7%) met criteria for alcohol use disorder, and these participants were more likely to be male, to smoke, and to have a history of rapid cycling, higher mean body mass index, and higher incidences of gastrointestinal and hepatobiliary morbidities. A multiple logistic regression analysis revealed that patients with, versus those without, alcohol use disorder were more prone to gastrointestinal diseases (adjusted OR = 4.25, 95% CI [1.44-12.53], p <.01), hepatobiliary diseases (adjusted OR = 3.14, 95% CI [1.20-8.25], p <.025), and history of rapid cycling (adjusted OR = 2.53, 95% CI [0.91-7.01], p <.075). CONCLUSIONS: Comorbid alcohol use disorders may have a stronger impact on physical health than on psychosocial or psychopathological outcomes of patients with bipolar disorder.

Excessive suicide mortality and risk factors for suicide among patients with heroin dependence.

BACKGROUND: The mortality risk is high among individuals dependent on heroin, and suicide is a severe consequence of long-term heroin use. We estimated the incidence of suicide mortality and its risk factors in a large Asian cohort with heroin dependence. METHODS: A consecutive series of 2750 inpatients dependent on heroin admitted to a psychiatric center in northern Taiwan between 1990 and 2010 were retrospectively enrolled as the study cohort. These patients were linked to the Taiwan National Mortality Database to obtain each mortality event. We determined the Standardized Mortality Ratio (SMR) for each cause of death. Among the deceased, 69 deaths were due to suicide (cases); 138 controls were randomly selected using risk-set density sampling based on a nested case-control design. We collected clinical information from subjects' medical records. Multivariate conditional logistic regression was employed to explore the correlates of suicide mortality. RESULTS: The findings showed a 7.9-fold SMR for all-cause mortality among heroin users compared to the general population while the SMR for suicide mortality was 16.2. Multivariate analysis showed that suicide attempt as the reason for the index admission (adjusted risk ratio [RR] = 4.29, p = 0.035) and depressive syndrome anytime during life (adjusted RR = 2.61, p = 0.019) were associated with the risk of suicide mortality. CONCLUSIONS: Individuals dependent on heroin are more likely to die of suicide compared to the general population. We recommend that clinical psychiatric staff carefully gather information related to the identified risk factors to prevent suicide among heroin users.

Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission.

OBJECTIVE: A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission. METHODS: Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission. RESULTS: In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode. CONCLUSIONS: Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels.

Inflammatory markers and their relationships with leptin and insulin from acute mania to full remission in bipolar disorder.

BACKGROUND: Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear. METHODS: Thirty-three healthy, bipolar I patients under 45 years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects. RESULTS: The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=-0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend. CONCLUSIONS: Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission.

Increased risk of acute myocardial infarction for patients with panic disorder: a nationwide population-based study.

OBJECTIVE: To examine prospectively the relationship between a diagnosis of panic disorder and the risk of acute myocardial infarction within 1 year of follow-up. Panic disorder is associated prospectively with coronary artery disease, but the risk of acute myocardial infarction associated with panic disorder has not been specifically investigated. METHOD: This nationwide population-based study used data from the Taiwan National Health Insurance Research Database covering the years 2000 to 2005. A total of 9641 patients diagnosed with panic disorder in 2004 were included, together with 28,923 matched nonpanic disorder enrollees as a comparison cohort. Cox proportional hazard regressions were conducted to compute hazard ratios, after adjustment for comorbid medical disorders and sociodemographic characteristics. RESULTS: Results indicated that 4.77% of patients with panic disorder (approximately one in 21) experienced an acute myocardial infarction episode within a year, compared with 2.73% of patients in the comparison cohort. The adjusted hazard of acute myocardial infarction was significantly higher (1.75 times, 95% Confidence Interval = 1.55-1.97) for patients with panic disorder, relative to the comparison cohort. The association persisted in further analyses stratified by hypertension, coronary heart diseases, and age. CONCLUSION: Panic disorder was identified as an independent risk factor for subsequent acute myocardial infarction. Comprehensive multidisciplinary approaches are needed to optimize primary and secondary prevention of acute myocardial infarction among patients with panic disorder.

Cognitive dysfunction and medical morbidity in elderly outpatients with bipolar disorder.

OBJECTIVE: The authors investigated the differences in cognitive function, medical burden, and sociodemographic characteristics between elderly community-dwelling bipolar patients and age-matched and education-matched normal individuals. DESIGN: Case-control study. SETTING: Taipei Medical University Hospital, with 75 psychiatric beds, and Taipei City Psychiatric Center-a 612-bed psychiatric teaching hospital providing comprehensive psychiatric services. PARTICIPANTS: Eighty-two euthymic outpatients with bipolar I disorder aged older than 60 years received assessment for research purpose, 59 of whom were matched with one normal control for age and years of education. MEASUREMENTS: All subjects had measurements of cognitive function (Clock-drawing test and Mini-Mental State Examination [MMSE]). Medical morbidity and health condition were according to the medical records, results of free annual elderly health examination, and physical examination on research interviewing. RESULTS: Elderly bipolar patients were found to be more likely than the comparison group to have diabetes mellitus (27.1%), atopic diseases (20.3%), abnormal education-adjusted MMSE scores (32.2%), smoking habit (23.7%), and unfavorable social functioning (22%). Despite having noticeably higher heart rates, the bipolar patients' mean systolic blood pressure and prevalence of hypertension (44.1%) were significantly lower than those of the comparison group. CONCLUSIONS: Although community-dwelling elderly patients with bipolar disorder seem to be characterized by a greater likelihood of developing cognitive dysfunction and concurrent diabetes mellitus, there is no apparent increase in the morbidity of circulatory diseases, particularly less hypertension among those without previous dementia.