Erick Messias

Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review.

Objective: Alzheimer’s disease, the most prevalent dementia, is a prominent source of chronic illness in the elderly. Laboratory evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the onset of Alzheimer’s disease. Since the early 1990s, numerous observational epidemiological studies have also investigated this possibility. The purpose of this meta-analysis is to summarize and evaluate available evidence regarding exposure to nonaspirin NSAIDs and risk of Alzheimer’s disease using meta-analyses of published studies. Methods: A systematic search was conducted using Medline, Biological Abstracts, and the Cochrane Library for publications from 1960 onwards. All cross-sectional, retrospective, or prospective observational studies of Alzheimer’s disease in relation to NSAID exposure were included in the analysis. At least 2 of 4 independent reviewers characterized each study by source of data and design, including method of classifying exposure and outcome, and evaluated the studies for eligibility. Discrepancies were resolved by consensus of all 4 reviewers. Results: Of 38 publications, 11 met the qualitative criteria for inclusion in the meta-analysis. For the 3 case-control and 4 cross-sectional studies, the combined risk estimate for development of Alzheimer’s disease was 0.51 (95% CI = 0.40–0.66) for NSAID exposure. In the prospective studies, the estimate was 0.74 (95% CI = 0.62–0.89) for the 4 studies reporting lifetime NSAID exposure and it was 0.42 (95% CI = 0.26–0.66) for the 3 studies reporting a duration of use of 2 or more years. Conclusions: Based on analysis of prospective and nonprospective studies, NSAID exposure was associated with decreased risk of Alzheimer’s disease. An issue that requires further exploration in future trials or observational studies is the temporal relationship between NSAID exposure and protection against Alzheimer’s disease.

Comorbidity of medical illnesses among adults with serious mental illness who are receiving community psychiatric services.

We studied the medical comorbidity among individuals with serious mental illness who were receiving community-based psychiatric treatment. A total of 200 psychiatric outpatients divided between those with schizophrenia and affective disorder diagnoses were recruited from samples receiving outpatient care at two psychiatric centers. Interviews used questions from national health surveys. Logistic regression analyses compared responses from each sample with those of matched subsets of individuals from the general population. Both patient groups had greater odds of having many medical conditions. The odds of respiratory illnesses remained elevated in the patient groups even after controlling for smoking, as did the odds of diabetes in the affective disorder group after controlling for weight. Persons with serious mental illness who are in outpatient care are more likely to have comorbid medical conditions than persons in the general population. The odds of diabetes, lung diseases, and liver problems are particularly elevated. These findings underscore the need for intensified preventive health interventions and medical services for this population.

Meta-analysis of Paternal Age and Schizophrenia Risk in Male Versus Female Offspring

INTRODUCTION Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. METHODS We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. RESULTS There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (≥30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (≥50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR = 1.08, 95% CI: 1.02-1.14, P = 0.01) but not females (RR = 1.04, 95% CI: 0.97-1.14, P = 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ≥30 and 5% for paternal age <25. DISCUSSION Both APA (≥30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies

Autoantibody formation directed against phospholipase A2 receptor (PLA2R)1 is the underlying etiology in most cases of primary membranous glomerulopathy. This new understanding of the pathogenesis of primary membranous is in the process of transforming the way the disease is diagnosed. We validated an indirect immunofluorescence assay to examine PLA2R1 in renal biopsies utilizing a commercially available antibody and standard indirect immunofluorescence. Using this assay, we examined a total of 165 cases of membranous glomerulopathy including 85 primary and 80 secondary. We found tissue staining for PLA2R1 to have a sensitivity of 75% (95% CI 65−84%) and a specificity of 83% (95% CI 72−90%) for primary membranous glomerulopathy. Hepatitis C virus was the secondary etiology with the most number of cases staining positive for PLA2R1 (7/11, 64%) followed by sarcoidosis (3/4, 75%) and neoplasm (3/12, 25%). Autoimmune etiologies showed rare PLA2R1-positive staining (1/46, 2%). All cases of secondary membranous glomerulopathy with positive PLA2R1 showed IgG4-predominant staining, which is typically associated with primary membranous glomerulopathy. This IgG4 predominance raises the possibility that these cases are more pathogenically related to primary membranous glomerulopathy than secondary. We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy utilizing a technique that is readily adoptable by most renal pathology laboratories.

Income inequality, illiteracy rate, and life expectancy in Brazil

OBJECTIVES The link between income disparities and health has been studied mostly in developed nations. This study assesses the relationship between income disparities and life expectancy in Brazil and measures the impact of illiteracy rates on the association. METHODS The units of analysis (n = 27) are all the Brazilian states and the federal capital. Simple and multiple linear regressions were performed to measure the association between income disparity, measured by the Gini coefficient, gross domestic product (GDP) per capita, and illiteracy rate. Data came from publicly available sources at the Brazilian Ministry of Health and the Brazilian Institute of Geography and Statistics. RESULTS Income disparities and illiteracy rates were negatively associated with life expectancy in Brazil. GDP per capita was positively associated with life expectancy. The inclusion of illiteracy rates in the regression model removed the effect of income disparities. CONCLUSIONS Illiteracy rate is strongly associated with life expectancy in Brazil. This finding is in accord with reports from the United States and has implications for health policy and planning for both developed and developing countries.

Teen Sleep and Suicidality: Results from the Youth Risk Behavior Surveys of 2007 and 2009

STUDY OBJECTIVES Suicide in the adolescent population is a tragic and preventable cause of death. Previous studies have confirmed both long and short total sleep times (TSTs) are associated with suicidal ideation in the adult population. We hypothesized that both long and short TSTs are risk factors for serious suicide attempt in the adolescent population as well. METHODS We tested this hypothesis using the Youth Risk Behavior Surveys from 2007 and 2009, which consist of school-based, nationally representative samples (N = 12,154 for 2007, N = 14,782 for 2009). Logistic regression models were used to assess the relationship between suicidality and sleep after adjusting for confounders including age, sex, race/ethnicity, feelings of sadness, and substance abuse. RESULTS Of the total sample, roughly 15% reported suicidal ideation, 10% planned suicide, 5% attempted and 2% reported an attempt requiring treatment. Teens who reported sleeping ≤ 5 or ≥ 10 h had a significantly higher risk for suicidality compared to those with a TST of 8 h. The largest odds ratios were found among the most severe forms of suicidality (attempt requiring treatment) with an odds ratio of 5.9 for a TST ≤ 4 h and 4.7 for a TST ≥ 10 h. CONCLUSION Both short and long TSTs are risk factors for suicidality among teens and extremes in TST may indicate more serious suicidality. Self-reported sleep duration may be a useful screening question for suicide risk. Future studies should examine whether sleep duration is a causal and/or modifiable risk factor for suicidality in teens.

Sadness, Suicide, and Their Association with Video Game and Internet Overuse among Teens: Results from the Youth Risk Behavior Survey 2007 and 2009

We investigated the association between excessive video game/Internet use and teen suicidality. Data were obtained from the 2007 and 2009 Youth Risk Behavior Survey (YRBS), a high school-based, nationally representative survey (N = 14,041 and N = 16,410, respectively). Teens who reported 5 hours or more of video games/Internet daily use, in the 2009 YRBS, had a significantly higher risk for sadness (adjusted and weighted odds ratio, 95% confidence interval = 2.1, 1.7-2.5), suicidal ideation (1.7, 1.3-2.1), and suicide planning (1.5, 1.1-1.9). The same pattern was found in the 2007 survey. These findings support an association between excessive video game and Internet use and risk for teen depression and suicidality.

School bullying, cyberbullying, or both: correlates of teen suicidality in the 2011 CDC youth risk behavior survey

While school bullying has been shown to be associated with depression and suicidality among teens, the relationship between these outcomes and cyberbullying has not been studied in nationally representative samples. Data came from the 2011 CDC Youth Risk Behavior Survey (YRBS), a nationally representative sample of high-school students (N=15,425). We calculated weighted estimates representative of all students in grades 9-12 attending school in the US. Logistic regression was used to calculate adjusted odds ratios. Overall, girls are more likely to be report being bullied (31.3% vs. 22.9%), in particularly to be cyberbullied (22.0% vs. 10.8%), while boys are only more likely to report exclusive school bullying (12.2% vs. 9.2%). Reports of 2-week sadness and all suicidality items were highest among teens reporting both forms of bullying, followed by those reporting cyberbullying only, followed by those reporting school bullying only. For example, among those reporting not being bullied 4.6% reported having made a suicide attempt, compared to 9.5% of those reporting school bullying only (adjusted odd ratio (AOR) 2.3, 95% C.I. 1.8-2.9), 14.7% of those reporting cyberbullying only (AOR 3.5 (2.6-4.7)), and 21.1% of those reporting victimization of both types of bullying (AOR 5.6 (4.4-7)). Bullying victimization, in school, cyber, or both, is associated with higher risk of sadness and suicidality among teens. Interventions to prevent school bullying as well as cyberbullying are needed. When caring for teens reporting being bullied, either at school or in cyberbullying, its important to screen for depression and suicidality.

Functional reorganization of neural networks during repeated exposure to the traumatic memory in posttraumatic stress disorder: an exploratory fMRI study.

BACKGROUND Repeated exposure to the traumatic memory (RETM) is a common component of treatments for posttraumatic stress disorder (PTSD). This treatment is based on a fear extinction model; however, the degree to which this treatment actually engages and modifies neural networks mediating fear extinction is unknown. Therefore, the purpose of the current exploratory study was to define the dynamic changes in neural processing networks while participants completed a novel adaptation of RETM. METHOD Participants were adult women (N = 16) with PTSD related to physical or sexual assault. Prior to scanning, participants provided written narratives of a traumatic event related to their PTSD as well as a neutral control event. RETM during fMRI consisted of 5 sequential presentations of the blocked narrative types, lasting three minutes each. Self-reported anxiety was assessed after each presentation. RESULTS Relative to changes in functional connectivity during the neutral control script, RETM was associated with strengthened functional connectivity of the right amygdala with the right hippocampus and right anterior insular cortex, left amygdala with the right insular cortex, medial PFC with right anterior insula, left hippocampus with striatum and dorsal cingulate cortex, and right hippocampus with striatum and orbitofrontal cortex. Greater PTSD severity generally led to less changes in functional connectivity with the right insular cortex. CONCLUSIONS These results provide evidence that RETM engages and modifies functional connectivity pathways with neural regions implicated in fear extinction. The results also implicate the engagement of the right insular cortex and striatum during RETM and suggest their importance in human fear extinction to trauma memories. However, comorbidity in the sample and the lack of a control group limit inferences regarding RETM with PTSD populations specifically.

Asthma and suicidal ideation with and without suicide attempts among adults in the United States: what is the role of cigarette smoking and mental disorders?

BACKGROUND Evidence of a respiratory diseases and suicidal ideation and suicide attempts link exists. To improve our understanding of the mechanism underlying these links, there is a need for examination of the relationship between specific respiratory disease, such as asthma, and suicidal ideation and behavior. In addition, studies need to examine many common risk factors that may play a role in the association between asthma and suicidal ideation and suicide behavior. OBJECTIVE To examine the association between asthma and suicidal ideation with and without attempts among adults in the United States, specifically investigating the role of cigarette smoking, nicotine dependence, depression, anxiety, and alcohol abuse. METHODS Data on 5,692 individuals 18 years and older were drawn from the US National Comorbidity Survey Replication. Descriptive and multivariate logistic regression analyses were conducted to examine the study objectives. RESULTS The estimates of lifetime prevalence for suicidal ideation without and with attempts and asthma were 8.7%, 4.2%, and 12.0%, respectively. Being a woman, a current smoker, depressed, anxious, an alcohol abuser, or nicotine dependent increased the likelihood of suicidal ideation with attempts and asthma. Asthma was significantly (P < .001) associated with suicidal ideation with but not without attempts. Adjustment for smoking, nicotine dependence, age, sex, and race/ethnicity decreased the association between asthma and suicidal ideation with attempts by 16%. Similarly, adjustment for depression, panic disorder, and alcohol abuse led to a 12.4% decrease in this relationship. Despite these adjustments, independently or combined, a statistically significant (P = .02) association remained between asthma and suicidal ideation with attempts. CONCLUSIONS Cigarette smoking and concurrent mental health conditions may independently account for significant proportions of the association between asthma and suicidal ideation with attempts. More research is needed to further elucidate the mechanism of the remaining association between asthma and suicide attempts. Modification of smoking behaviors and effective treatment of depression, anxiety, alcohol abuse, and possibly asthma are important suicide prevention strategies.