Search

Objective To identify the determinants of natural cause mortality in a cohort of individuals with serious mental illness assessed prospectively. Method Persons with schizophrenia (n = 789) and bipolar disorder (n = 498), mean age of 38 (s.d. 12.6) years, underwent an in-person clinical assessment. They also had a blood sample drawn from which infectious disease markers were measured. Mortality was subsequently determined utilizing data from the National Death Index following a period of up to 16.9 years. Results A total of 6.8% (87 of 1287) of persons died of natural causes. Mortality was predicted in a multivariate model by baseline cigarette smoking (RR = 6.29, 95% CI 1.41, 3.72, P = 0.00076); divorced or widowed status (RR = 1.90, CI 1.21, 2.99); reduced cognitive score (RR = 0.73, CI 0.61, 0.87); receipt of antidepressant medication (RR = 1.74, CI 1.12, 2.71); elevated levels of antibodies to Epstein-Barr virus (EBV) (RR = 1.29, CI 1.01, 1.66); and a genitourinary (RR = 1.82, CI 1.16, 2.86), respiratory (RR = 1.82, CI 1.16, 2.86), or cardiac (RR = 2.09, CI 1.33, 3.29) condition. There was an additive effect of smoking and both a cardiac and a respiratory condition but not elevated EBV antibody levels. Conclusion Smoking is a modifiable behaviour which is associated with mortality in this population.

Objectives We have preciously documented that many individuals with acute mania have immune activation. However, the sources of immune activation have not been identified. We investigated whether individuals hospitalized with acute mania have evidence of bacterial infections as determined by the prescription of systemic antimicrobial agents. Methods We assessed the recent prescription of systemic antimicrobial medications and the site of presumed bacterial infection in 234 individuals hospitalized for acute mania in either an inpatient unit or a day hospital. We also assessed individuals hospitalized for other psychiatric disorders (n=368) and controls (n=555). We employed logistic regression models to compare the rates of antibiotic prescription in individuals with the different diagnoses, employing demographic variables as covariates. Results We found that individuals hospitalized with acute mania had a substantially increased rate of recent antimicrobial prescription, defined as exposure within three days of ascertainment (adjusted odds ratio=5.5, 95% confidence interval: 2.2–14.1, P

Objectives Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder. Methods We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n = 207), in patients with bipolar disorder without a recent onset of psychosis (n = 226), and in patients with bipolar disorder with a recent onset of psychosis (n = 38). We compared ASCA levels to antibodies against gluten, casein, Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV-1), influenza A, influenza B, measles, and Toxoplasma gondii. Results Elevated ASCA conferred a 3.5–4.4-fold increased odds ratio of disease association (age-, race-, and gender-corrected multinomial logistic regressions, p ≤ 0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar disorder groups (R2 = 0.29–0.59, p ≤ 0.0005), and with measles and T. gondii immunoglobulin G (IgG) in the recent onset psychosis bipolar disorder group (R2 = 0.31–0.36, p ≤ 0.004–0.01). Conclusions Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggest a GI comorbidity in at least a subgroup of individuals with bipolar disorder. Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder.

Dickerson F, Stallings C, Vaughan C, Origoni A, Khushalani S, Yolken R. Antibodies to the glutamate receptor in mania. Bipolar Disord 2012: 14: 547–553. © 2012 The Authors.Journal compilation © 2012 John Wiley & Sons A/S. Background: There is evidence that the glutamatergic system is involved in the pathophysiology of mania. Antibodies to the NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor have been shown to adversely affect glutamate functioning. Methods: We measured serum antibodies to the NR2 peptide of the NMDA receptor in 60 individuals with different subtypes of mania, including schizoaffective cases, who were assessed at up to three time points. We also measured these antibodies in 295 individuals in other psychiatric groups and in 170 non-psychiatric controls. NR2 antibody levels were compared among groups by multivariate analyses and within the mania group by repeated measures analysis of variance. Results: Individuals with mania had increased levels of antibodies to the NR2 peptide compared to levels in non-psychiatric controls when measured at the time of admission (t = 2.99, p = 0.003) and the time of evaluation (t = 2.57, p = 0.010), but not at follow-up six months later. The levels of antibodies in individuals in other psychiatric groups did not differ significantly from the levels measured in the control population. Within the mania group, there was a significant decrease in antibody levels over the three time points of the study (F = 5.4, df = 2, p = 0.0067). Conclusions: NR2 antibodies are elevated during the acute phase of mania but not at follow-up. Our findings support a role for antibodies to the NMDA receptor in the pathogenesis of acute mania.

Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Alaedini A, Yolken R. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disord 2011: 13: 52–58. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Increased immune sensitivity to dietary gluten proteins has been reported in schizophrenia but has not been studied in bipolar disorder. In this study, we examine the levels of antibody reactivity to gliadin, deamidated gliadin, and tissue transglutaminase (tTG) in individuals with bipolar disorder and compare these levels to those in individuals who do not have any history of psychiatric disorder. Methods: The sample of 275 individuals included 102 with bipolar disorder and 173 controls without a psychiatric disorder. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to gliadin and tTG and IgG antibodies to deamidated gliadin were measured by enzyme immunoassay. Participants’ levels of antibodies to deamidated gliadin and tTG were classified based on the cutoffs for positivity that are predictive of celiac disease. Quantitative levels of antibodies were compared between groups employing regression models which were controlled for demographic variables. Results: Individuals with bipolar disorder had increased levels of IgG antibodies to gliadin compared with controls in multivariate analyses. We also found evidence of increased levels of antibodies to deamidated gliadin in the bipolar disorder population. The levels of IgA class antigliadin antibodies and antibodies to tTG did not differ significantly between groups. There was also not a significant difference between groups in the number of persons who were classified as having levels of antibodies to deamidated gliadin or tTG that are predictive of celiac disease. Conclusions: Individuals with bipolar disorder have increased levels of IgG antibodies to gliadin. However, such antibody increase is not accompanied by an elevation in IgA antibodies to gliadin or the celiac disease-associated antibodies against deamidated gliadin and tTG. These results warrant further detailed examination of the molecular specificity and pattern of reactivity of the antibody response to gluten antigens in bipolar disorder.

Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals. Methods: Anti-bovine casein immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75 individuals with bipolar disorder and 65 controls. Epitope recognition was evaluated in immunoassays by cross neutralization with anti-bovine casein polyclonal antibodies of defined reactivity. Group-specific reactivity and associations with symptom severity scores were detected with age-, gender-, and race-controlled regression models. Results: Individuals with bipolar disorder had significantly elevated anti-casein IgG (t-test, p = 0.001) compared to controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar disorder [n = 75, 95% confidence interval (CI): 1.31–12.08, p = 0.015], 5.26 for the bipolar I subtype (n = 56, 95% CI: 1.66–16.64, p = 0.005), and 3.98 for bipolar disorder with psychosis (n = 54, 95% CI: 1.32–12.00, p = 0.014). Lithium and/or antipsychotic medication did not significantly affect anti-casein IgG levels. Casein IgG measures correlated with severity of manic (R2 = 0.15, 95% CI: 0.05–0.24, p = 0.02) but not depressive symptoms. Unlike controls, sera from individuals with bipolar disorder did not inhibit binding of casein-reactive animal sera (t-test/?2, p = 0.0001). Conclusions: Anti-casein IgG associations with bipolar I diagnoses, psychotic symptom history, and mania severity scores suggest that casein-related immune activation may relate to the psychosis and mania components of this mood disorder. Case-control differences in epitope recognition implicate disease-related alterations in how the casein molecule is digested and/or how resulting casein-derived structures are rendered immunogenic.

Dickerson F, Origoni A, Stallings C, Khushalani S, Dickinson D, Medoff D. Occupational status and social adjustment six months after hospitalization early in the course of bipolar disorder: a prospective study. Bipolar Disord 2010: 12: 10–20. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Bipolar disorder is often accompanied by poor functional outcomes, the determinants of which are not fully understood. We assessed patients with bipolar disorder undergoing a hospital admission early in the illness course and identified predictors of occupational status, overall social adjustment, and work adjustment six months later. Methods: This was a prospective longitudinal cohort study. During hospitalization patients were evaluated with a cognitive battery; symptoms, occupational history, and other clinical factors were also assessed. At six-month follow-up, patients’ symptom remission status was assessed; they were also evaluated as to their occupational status, overall social adjustment, and work adjustment. Multivariate analyses were used to identify predictors of these outcomes. Results: Among the 52 participants, the average rating of overall social adjustment at follow-up was between mild and moderate maladjustment. While 51 had a history of working full time, only 28 (54%) worked full time at follow-up. A total of 24 (46%) had symptoms that met criteria for a full depression or mania syndrome. In multivariate analyses, full-time occupational status at follow-up was predicted by the absence of baseline substance abuse. Better overall social adjustment was predicted by better performance on cognitive tasks of processing speed and by symptom remission; the latter variable also predicted work adjustment. Conclusions: Persons with bipolar disorder have limited occupational recovery and overall social adjustment six months after a hospital admission early in the illness course. Predictors vary among outcomes; performance on tasks of processing speed and the extent of symptom remission are independently associated with functional outcomes.

Background: Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder. Methods: We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions. Results: The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association. Conclusion: Both the COMT Val158Met polymorphism and serological evidence of HSV-1 infection affect cognitive functioning in individuals with bipolar disorder.

Concilian el trabajo profesional y la familia? Los autores estudian si la cultura de una region o un pais ejerce una influencia palpable en las decisiones de las mujeres de incorporarse o no al mercado laboral y de trabajar a tiempo completo o a tiempo parcial. El articulo versa sobre la poblacion femenina de Suiza, un pais dividido en tres regiones de cultura germanica, francesa e italiana, y situado entre las zonas meridional y septentrional de Europa. Los autores comprueban que son diferentes las posturas de las mujeres de las tres regiones en materia de familia y trabajo, gracias a un sistema innovador de arboles de clasificacion estadistica que reviste un gran interes metodologico.

Department of Obstetrics and Gynaecology, Insubria University, Varese, ItalyAim: To report the debate on the relationship between overactive bladder (OAB) in children and adults during theICI-RS meeting in 2010. Methods: Literature supporting or being against the theory that OAB in children and adultsrepresents the same condition has been reviewed and debated. Results: Growing evidence is showing a strong linkbetween urinary symptoms in childhood, such as nocturnal enuresis (NE) and OAB symptoms, and OAB in adulthood.Behavioral and environmental factors may have an important role in predisposed subjects. Studies on familial andgenetic factors have been reported. Conclusion: It might be inappropriate to state that OAB in children and adultsrepresents the same condition. However, epidemiological and genetic findings demonstrate a strong link between OABsymptoms in these two different ages of life. Predisposing factors and behavioral and/or environmental elements maylead to OAB occurrence in adults. Neurourol. Urodynam. 31:349–351, 2012. 2012 Wiley Periodicals, Inc.

Cervical neoplastic lesions are associated with infection by high-risk human papilloma-viruses (HPV). The two genotypes most frequently found in the lesions are HPV-16 and HPV-18 with a prevalence of 50-60% and 15-18%, respectively. The E6 and E7 viral oncoproteins are involved in the transformation process and represent foreign antigens for the host. We previously reported that anti-HPV-18 E6 CD4(+) T cells are present in patients with high-grade HPV-18-expressing cervical lesions but also in 50% of the total consecutive patients tested, independently of the HPV type carried. These results indicated that HPV-18 E6 is immunogenic and suggested that all responsive patients, irrespective of the HPV expressed, had encountered HPV-18 and cleared the infection. Here, we investigated anti-HPV-18 E7 CD4(+) T-cell immunity in a cohort of 23 HPV-18 E6-responsive patients. We found that, although E7-specific CD4(+) T cells were present in all women, a robust T helper type (Th1)/Th2 type response against E7 was associated with HPV-18-negative status, suggesting that indeed these patients might have cleared the virus. In agreement with this hypothesis, we found strong anti-E7 CD4(+) T-cell immunity in 20% of 24 healthy donors without evidence of disease. In contrast, a robust Th1/Th2 type response against E6 but not E7 correlated with a lack of disease relapse and/or infection recurrence but did not discriminate between HPV-18-positive and HPV-18-negative patients. Collectively, our data suggest different roles for anti-HPV-18 E6 and E7 CD4(+) T cells in anti-viral and anti-tumour immunity.