Lifetime experience of multiple common mental disorders and 19-year mortality: results from a Canadian population-based cohort.

AIMS: To examine the impact of multiple psychiatric disorders over the lifetime on risk of mortality in the general population. METHODS: Data came from a random community-based sample of 1397 adults in Atlantic Canada, recruited in 1992. Major depression, dysthymia, panic disorder, generalised anxiety disorder and alcohol use disorders were assessed using the Diagnostic Interview Schedule (DIS). Vital status of participants through 2011 was determined using probabilistic linkages to the Canadian Mortality Database. Cox proportional hazard models with age at study entry as the time scale were used to investigate the relationship between DIS diagnoses and mortality, adjusted for participant education, smoking and obesity at baseline. RESULTS: Results suggested that mood and anxiety disorders rarely presented in isolation - the majority of participants experienced multiple psychiatric disorders over the lifetime. Elevated risk of death was found among men with both major depression and dysthymia (HR 2.56; 95% CI 1.12-5.89), depression and alcohol use disorders (HR 2.45; 95% CI 1.18-5.10) and among men and women who experienced both panic disorder and alcohol use disorders (HR 3.80; 95% CI 1.19-12.16). CONCLUSION: The experience of multiple mental disorders over the lifetime is extremely common, and associated with increased risk of mortality, most notably among men. Clinicians should be aware of the importance of considering contemporaneous symptoms of multiple psychiatric conditions.

Eating disorder behaviours amongst adolescents: investigating classification, persistence and prospective associations with adverse outcomes using latent class models.

Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity.

Childhood hyperactivity/inattention and eating disturbances predict binge eating in adolescence.

BACKGROUND: Identifying childhood predictors of binge eating and understanding risk mechanisms could help improve prevention and detection efforts. The aim of this study was to examine whether features of attention-deficit/hyperactivity disorder (ADHD), as well as childhood eating disturbances, predicted binge eating later in adolescence. METHOD: We studied specific risk factors for the development of binge eating during mid-adolescence among 7120 males and females from the Avon Longitudinal Study of Parents and Children (ALSPAC), a cohort study of children in the UK, using data from multiple informants to develop structural equation models. Repeated assessment of eating disturbances during childhood (mid-childhood overeating, late-childhood overeating and early-adolescent strong desire for food), as well as teacher- and parent-reported hyperactivity/inattention during mid- and late childhood, were considered as possible predictors of mid-adolescent binge eating. RESULTS: Prevalence of binge eating during mid-adolescence in our sample was 11.6%. The final model of predictors of binge eating during mid-adolescence included direct effects of late-childhood overeating [standardized estimate 0.145, 95% confidence interval (CI) 0.038­0.259, p = 0.009] and early-adolescent strong desire for food (standardized estimate 0.088, 95% CI −0.002 to 0.169, p = 0.05). Hyperactivity/inattention during late childhood indirectly predicted binge eating during mid-adolescence (standardized estimate 0.085, 95% CI 0.007­0.128, p = 0.03) via late-childhood overeating and early-adolescent strong desire for food. CONCLUSIONS: Our findings indicate that early ADHD symptoms, in addition to an overeating phenotype, contribute to risk for adolescent binge eating. These findings lend support to the potential role of hyperactivity/inattention in the development of overeating and binge eating.

Body satisfaction, weight gain and binge eating among overweight adolescent girls.

OBJECTIVE: To examine if body satisfaction is associated with body mass index (BMI) change and whether it protects against the development of frequent binge eating among overweight and obese adolescent girls. METHODS: We used prospective data from nine waves of an ongoing cohort study of adolescents, the Growing Up Today Study. At enrollment in 1996, participants were 9-14 years old. Questionnaires were mailed to participants annually until 2001, then biennially through 2007. Girls who were overweight or obese in 1996 were included in the analysis (n = 1559). Our outcomes were annual change in BMI and incident frequent binge eating, defined as binge eating at least weekly and no use of compensatory behaviors. RESULTS: At baseline, 57.2% of the overweight and obese girls were at least somewhat satisfied with their bodies. During 11 years of follow-up, 9.5% (95% confidence interval (CI) (7.8, 10.8)) of the girls started to binge eat frequently. Controlling for BMI and other confounders, overweight and obese girls who reported being at least somewhat satisfied with their bodies made smaller BMI gains (ß = -0.10 kg m(-2), 95% CI (-0.19, -0.02)) and had 61% lower odds of starting to binge eat frequently (odds ratio (OR) = 0.39, 95% CI (0.24, 0.64)) than their less satisfied peers. Compared with girls who were the least satisfied with their bodies, girls who were the most satisfied had 85% lower odds of starting to binge eat frequently (OR = 0.15, 95% CI (0.06, 0.37)). The association between body satisfaction and starting to binge eat frequently was stronger for younger adolescents than older adolescents. CONCLUSIONS: Whereas body dissatisfaction is common among overweight and obese girls, body satisfaction may protect against excessive weight gain and binge eating. Prevention of body dissatisfaction must begin early and should be considered as a component of both obesity and eating disorder prevention programs.

Obesity and weight gain in relation to depression: findings from the Stirling County Study.

OBJECTIVE: This study concerns the question of whether obese subjects in a community sample experience depression in a different way from the nonobese, especially whether they overeat to the point of gaining weight during periods of depression. DESIGN: A representative sample of adults was interviewed regarding depression and obesity. SUBJECTS: The sample consisted of 1396 subjects whose interviews were studied regarding relationships between obesity and depression and among whom 114 had experienced a major depressive episode at some point in their lives and provided information about the symptoms experienced during the worst or only episode of major depression. MEASUREMENTS: The Diagnostic Interview Schedule (DIS) was used to identify major depressive episodes. Information was also derived from the section on Depression and Anxiety (DPAX) of the Stirling Study Schedule. Obesity was calculated as a body mass index >30. Logistic regressions were employed to assess relationships, controlling for age and gender, by means of odds ratios and 95% confidence intervals. RESULTS: In the sample as a whole, obesity was not related to depression although it was associated with the symptom of hopelessness. Among those who had ever experienced a major depressive episode, obese persons were 5 times more likely than the nonobese to overeat leading to weight gain during a period of depression (P<0.002). These obese subjects, compared to the nonobese, also experienced longer episodes of depression, a larger number of episodes, and were more preoccupied with death during such episodes. CONCLUSIONS: Depression among obese subjects in a community sample tends to be more severe than among the nonobese. Gaining weight while depressed is an important marker of that severity. Further research is needed to understand and possibly prevent the associations, sequences and outcomes among depression, obesity, weight gain and other adversities.

Physical and sexual violence and health care utilization in HIV-infected persons with alcohol problems.

We examined interpersonal violence and its association with health care utilization and substance use severity among a cohort of 349 HIV-infected men and women with histories of alcohol problems assessed biannually up to 36 months. Data included demographics, lifetime interpersonal violence histories, age at first violence exposure, recent violence (prior six months), substance use severity and health care utilization (ambulatory visits, Emergency Department (ED) visits, hospitalizations) and adherence to HIV medication. Kaplan-Meier survival curves estimated the proportion of subjects experiencing recent violence. Generalized estimating equation regression models evaluated the relationship between recent violence, utilization and substance use severity over time, controlling for demographics, CD4 counts and depressive symptoms. Subject characteristics included: 79% male; mean age 41 years; 44% black, 33% white and 23% other. Eighty percent of subjects reported lifetime interpersonal violence: 40% physical violence alone, and 40% sexual violence with or without physical violence. First violence occurred prior to age 13 in 46%. Twenty-four (41%) of subjects reported recent violence by 24 and 36 months, respectively. In multivariate analyses, recent violence was associated with more ambulatory visits, ED visits and hospitalizations and worse substance use severity, but not medication adherence. Due to the high incidence and associated increased health care services utilization, violence prevention interventions should be considered for HIV-infected patients with a history of alcohol problems.

Parental IQ and cognitive development of malnourished Indonesian children.

A cross-sectional study of children in West Kalimantan, Indonesia, was conducted to examine the relationship between malnutrition history, child IQ, school attendance, socioeconomic status, parental education and parental IQ. In unadjusted analyses, severely stunted children had significantly lower IQ scores than mild-moderately stunted children. This effect was significant when stunting, school attendance and parental education were included in multivariable models but was attenuated when parental IQ was included. Our research underscores the importance of accounting for parental IQ as a critical covariate when modeling the association between childhood stunting and IQ.

Anxiety and depression: a 40-year perspective on relationships regarding prevalence, distribution, and comorbidity.

OBJECTIVE: Building on a report about the prevalence of depression over time, this paper examines historical trends regarding anxiety in terms of its prevalence, its distribution by age and gender, and its comorbidity with depression. Methods for conducting such time trend analysis are reviewed. METHOD: Representative samples of adults were selected and interviewed in 1952, 1970, and 1992. Logistic regressions were used for statistical analysis. RESULTS: Although twice as common as depression, the prevalence of anxiety was equally stable. Anxiety was consistently and significantly more characteristic of women than men. A re-distribution of rates in 1992 indicated that depression but not anxiety had significantly increased among younger women (P = 0.03). Throughout the study, approximately half of the cases of anxiety also suffered depression. CONCLUSION: The relationships between anxiety and depression remained similar over time with the exception that depression came to resemble anxiety as a disorder to which women were significantly more vulnerable than men. Social and historical factors should be investigated to assess their relevance to this change.

The onset of HIV infection in the Leningrad region of Russia: a focus on drug and alcohol dependence.

OBJECTIVES: Within 5 years, 5 million Russians may be infected with HIV. Currently, injection drug use is the major risk factor for HIV. As Russia's alcohol consumption per capita is among the highest in the world, alcohol-associated behaviours may be an important contributor to the HIV epidemic. Our objective was to examine the prevalence of HIV infection among drug- and alcohol-dependent patients in a regional narcology hospital and in the general population in Leningrad. METHODS: All patients in the Narcology Hospital, Leningrad Regional Center of Addictions (LRCA), were tested for HIV antibody between 1997 and 2001. We reviewed these clinical records (i.e. serostatus, gender, age, and addiction) and data from the HIV/AIDS Center in the Leningrad Region (1997-2001). RESULTS: From 1997 to 2001, HIV prevalence at the LRCA increased from 0 to 12.7% overall, 33.4% among drug-dependent patients and 1.2% among alcohol-dependent patients. During the same 5-year period (1997-2001), 2826 persons were registered at the HIV/AIDS Center: 6, 6, 51, 780, and 1983 persons in 1997, 1998, 1999, 2000 and 2001, respectively. CONCLUSIONS: HIV infection is exploding in the Leningrad Region, currently in injection drug users (IDUs) but potentially more broadly. The known high per capita alcohol intake in Russia heightens concern regarding the sexual transmission of HIV. Interventions to prevent such a development should include use, and assessment of the effectiveness, of known HIV prevention measures for at-risk and infected individuals.

Association of alcohol consumption with HIV sex- and drug-risk behaviors among drug users.

The relationship between alcohol use and HIV transmission is well recognized but not fully understood. In particular, the role of alcohol abuse as a mediator of HIV risk behavior among drug users is not well documented. We hypothesized that alcohol use in drug users will result in greater HIV risk-taking behavior. Participants were 354 drug users, of whom 105 were recent injection drug users. Multiple regression models were used to characterize whether measures of sexual and injection drug use HIV risk behavior were related to alcohol consumption, controlling for other potentially associated factors. We found that sexual HIV risk-taking behavior is associated with increased alcohol consumption among women (p = 0.02), with women having more risky sexual behavior than males. However, contrary to our hypothesis, there was no significant association of alcohol consumption with risky injection drug behavior. Addressing alcohol problems among drug users, particularly women, may be an important opportunity to reduce HIV sexual risk behavior among this high-risk population.

Multiple informants: mortality associated with psychiatric disorders in the Stirling County Study.

This paper applies new statistical procedures for analyzing multiple-source information about the relation of psychiatric diagnoses to mortality. The data come from the Stirling County Study, a longitudinal community investigation of adults, that collected multiple-source reports (self-report and physician-report) about psychiatric disorders. These reports are used as predictors of mortality risk over a 16-year follow-up period (1952-1968). Despite extensive efforts, one or both of these reports were sometimes missing. Missingness of self-report was related to demographic characteristics as well as to physician-reports of psychiatric diagnosis. The statistical procedures used here draw together into a single frame of reference both informant reports for the initial Stirling survey and relate these to mortality risk using weighted generalized estimating equation regression models for time to event data. This unified method has two advantages over traditional approaches: 1) the relative predictiveness of each informant can be assessed and 2) all subjects contribute to the analysis. The methods are applicable to other areas of epidemiology where multiple informant reports are used. The results for self-reports and physician-reports of disorders were comparable: Psychiatric diagnosis was associated with higher mortality, particularly among younger subjects.

Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.

The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T(1)-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans.

Maximum likelihood analysis of logistic regression models with incomplete covariate data and auxiliary information.

This article presents a new method for maximum likelihood estimation of logistic regression models with incomplete covariate data where auxiliary information is available. This auxiliary information is extraneous to the regression model of interest but predictive of the covariate with missing data. Ibrahim (1990, Journal of the American Statistical Association 85, 765-769) provides a general method for estimating generalized linear regression models with missing covariates using the EM algorithm that is easily implemented when there is no auxiliary data. Vach (1997, Statistics in Medicine 16, 57-72) describes how the method can be extended when the outcome and auxiliary data are conditionally independent given the covariates in the model. The method allows the incorporation of auxiliary data without making the conditional independence assumption. We suggest tests of conditional independence and compare the performance of several estimators in an example concerning mental health service utilization in children. Using an artificial dataset, we compare the performance of several estimators when auxiliary data are available.

The relationship of prenatal and perinatal complications to cognitive functioning at age 7 in the New England Cohorts of the National Collaborative Perinatal Project.

Previous literature shows that children who later develop schizophrenia have elevated rates of prenatal and perinatal complications (PPCs) and neuropsychological deficits in childhood. However, little is known about the relationship of these risk factors to each other. We evaluated the relationship between PPCs and neuropsychological functioning at age 7 in a large epidemiological study of pregnancy, birth, and development: the National Collaborative Perinatal Project (NCPP). Thirteen standardized measures of cognitive abilities were acquired on 11,889 children at approximately age 7. Principal components analysis was used to create three neuropsychological measures: academic achievement skills, verbal-conceptual abilities, and perceptual-motor abilities. We measured the relationship between these factors and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic complications, and chronic hypoxia. All three measures of PPCs were significantly associated with lower neuropsychological performance, after controlling for various confounders. LBW had the strongest association with neuropsychological performance, followed by an index of presumed hypoxic insults. The effect sizes between PPCs and cognitive factors at age 7 were consistently largest with perceptual-motor abilities, followed by academic achievement skills and verbal-conceptual abilities. Future studies will evaluate the effects of specific PPCs and genetic risk factors for psychosis on cognitive functioning in childhood.

Impact of genetic vulnerability and hypoxia on overall intelligence by age 7 in offspring at high risk for schizophrenia compared with affective psychoses.

Risk factors for schizophrenia, such as genetic vulnerability and obstetric complications, have been associated with cognitive deficits in schizophrenia. We tested the association of these risk factors with general intellectual ability in offspring at high risk for psychoses and normal control subjects. Offspring of 182 parents with DSM-IV schizophrenia or affective psychoses were recruited and diagnosed from the Boston and Providence cohorts of the National Collaborative Perinatal Project (NCPP). Control subjects from the NCPP were selected to be comparable with affected parents based on the parent's age, ethnicity, study site, number of offspring enrolled in the NCPP, and payment status, and on the offspring's age, sex, and history of obstetric complications. Based on data prospectively acquired from pregnancy and events of gestation, labor, delivery, and the neonatal period, we derived a measure of probable hypoxic-ischemic insult. We also report on standardized measures of general intelligence (intelligence quotient [IQ]) collected at age 7. General linear mixed models were used to test for the simultaneous effects of genetic vulnerability, defined as parental diagnosis, and probable hypoxic insult on age 7 IQ. Specificity of the effects for schizophrenia compared with affective psychoses and sex effects were also tested. Low IQ at age 7 was significantly associated with genetic vulnerability to psychoses, in particular with schizophrenia.

Maximum likelihood analysis of generalized linear models with missing covariates.

Missing data is a common occurrence in most medical research data collection enterprises. There is an extensive literature concerning missing data, much of which has focused on missing outcomes. Covariates in regression models are often missing, particularly if information is being collected from multiple sources. The method of weights is an implementation of the EM algorithm for general maximum-likelihood analysis of regression models, including generalized linear models (GLMs) with incomplete covariates. In this paper, we will describe the method of weights in detail, illustrate its application with several examples, discuss its advantages and limitations, and review extensions and applications of the method.

Goodness-of-fit for GEE: an example with mental health service utilization.

Suppose we use generalized estimating equations to estimate a marginal regression model for repeated binary observations. There are no established summary statistics available for assessing the adequacy of the fitted model. In this paper we propose a goodness-of-fit test statistic which has an approximate chi-squared distribution when we have specified the model correctly. The proposed statistic can be viewed as an extension of the Hosmer and Lemeshow goodness-of-fit statistic for ordinary logistic regression to marginal regression models for repeated binary responses. We illustrate the methods using data from a study of mental health service utilization by children. The repeated responses are a set of binary measures of service use. We fit a marginal logistic regression model to the data using generalized estimating equations, and we apply the proposed goodness-of-fit statistic to assess the adequacy of the fitted model.