Distribution-Based Causal Inference : A Review and Practical Guidance for Epidemiologists

Peer reviewe

Symptom-level analysis of depression and functional impairment : Evidence from population-based studies

Depression is a common and disabling mental disorder. Empirical studies have shown that depressive symptoms vary substantially according to antecedents and outcome variables. Nevertheless, research is most often reduced to symptom counts and clinical settings. One of the limitations is the lack of knowledge about the presentation of individual symptoms and their association with clinically relevant outcomes, such as severe functional impairment. The heterogeneity of the symptoms may be an important source of information for a better understanding of depression. This thesis aims to produce empirical insights on how individual depressive symptoms relate to severe functional impairment in community-based samples. In this doctoral dissertation, we used symptom-level data from two large epidemiologic studies that are representative of the population of the United States: the Collaborative Psychiatric Epidemiology Surveys (CPES), and the National Health and Nutrition Examination Survey (NHANES). Our results suggest that, in terms of statistical fit, sum-scores functioned almost as efficiently as symptom-level modeling in predicting self-rated functional impairment. However, examining symptoms individually offered a more detailed understanding of depression as a syndrome. For instance, symptom-level analyses revealed that age group moderated the associations of three symptoms with severe impairment. According to our results, middle-aged adults were more prone to feel severely impaired by these symptoms, as compared to adults aged 30 and below and in retirement age. The symptoms were depressed mood, self-criticism, and impaired concentration. Additionally, some symptoms did not have a significant association with high functional impairment in a fully adjusted model. This suggests that the association with impairment runs through other symptoms. In general, we found that cognitive-affective symptoms of depression related consistently to severe functional impairment. Among them, self-criticism emerged as particularly informative for its consistent association with high functional impairment across analyses, and for its effect on other symptoms as revealed by cross-sectional direction of dependence analyses. A practical implication of this is that supporting individuals’ self-worth may protect against the development of depressive symptomatology and its corresponding impact on functioning. Our findings motivate considering a wider range of symptoms, both in terms of severity and content, for further understanding the heterogeneity of depression. Similarly, functional impairment as a core component of severity calls for systematic exploration, and for a more refined measurement. A better characterization of the severity of depression as a continuum is fundamental for theoretical developments in psychopathology, and potentially useful for planning more efficient interventions targeting the most disabling, dominant symptoms.Masennus on yleinen, toimintakykyä vakavasti rajoittava sairaus. Aikaisemmassa tutkimuksessa masennusta ja sen vaikeusastetta on tarkasteltu pääasiassa masennusoireiden yhteenlasketun lukumäärän mukaan. Rajoituksena tässä lähestymistavassa on se, että siinä sivuutetaan yksittäisten oireiden esiintyminen sekä yksittäisten oireiden ja masennuksen vaikeusasteen yhteys. Aikaisemman tutkimuksen perusteella kuitenkin tiedetään, että masennusoireiden riskitekijät ovat erilaisia ja masennusoireet ennustavat erilaisia lopputulemia. Onkin mahdollista, että tämän oiretasoisen variaation ymmärtäminen on avainasemassa masennuksen ymmärtämisessä. Tässä väitöstutkimuksessa tarkasteltiin yksittäisten masennusoireiden ja vakavan toimintakyvyn menetyksen yhteyttä väestötasolla. Tutkimuksen aineisto koostui kahdesta laajasta yhdysvaltalaisesta väestötutkimuksesta. Tutkimuksen tulosten mukaan masennusoireiden lukumäärä ennusti vakavaa toimintakyvyn menetystä lähes yhtä hyvin kuin yksittäiset masennusoireet. Yksittäisten masennusoireiden tarkastelu paljasti, että varsinkin kognitiiviset ja affektiiviset masennusoireet olivat johdonmukaisesti yhteydessä heikkoon toimintakykyyn. Lisäksi, keski-ikäisillä masentunut mieliala, itsekriittisyys ja keskittymisvaikeudet olivat yhteydessä toimintakyvyn menetykseen voimakkaammin, verrattuna nuoriin tai iäkkäisiin. Näistä oireista itsekriittisyys nousi tutkimuksen tuloksissa merkittävimpään asemaan, sillä se oli selkeästi yhteydessä paitsi toimintakykyyn, myös muihin masennusoireisiin. Myötätuntoisen asennoitumisen kehittäminen itseä kohtaan saattaa siten suojata masennuksen kehittymiseltä ja masennukseen liittyvältä toimintakyvyn heikkenemiseltä. Tutkimuksen tuloksia voidaan hyödyntää esimerkiksi masennuksen mallien ja hoidon kehittämisessä. Huomion kohdentamisesta keskeisimpiin masennusoireisiin voi olla hyötyä masennuksen hoitamisessa

The varying burden of depressive symptoms across adulthood : Results from six NHANES cohorts

Background: Depressive symptoms differ from each other in the degree of functional impairment they cause. The incidence of depression varies across the adult lifespan. We examined whether age moderates the impairment caused by depressive symptoms. Methods: The study sample (n = 21,056) was adults drawn from six multistage probability samples from the National Health and Nutrition Examination Survey series (NHANES, years 2005-2016) conducted in the United States using cross-sectional, representative cohorts. Depressive symptoms were assessed with the nine-item Patient Health Questionnaire (PHQ-9). We used regression models to predict high functional impairment, while controlling for sociodemographic variables and physical disorders. Results: Age moderated the association between depressive symptoms and functional impairment: middle-aged adults perceived moderate and severe symptoms as more impairing than did others. Older adults reported slightly higher impairment due to mild symptoms. The individual symptoms of low mood, feelings of worthlessness and guilt, and concentration difficulties were more strongly related to high impairment in mid-adulthood as compared to early and late adulthood. Limitations: Cross-sectional data allows only between-person comparisons. The PHQ-9 is brief and joins compound symptoms into single items. There was no information available concerning comorbid mental disorders. Co-occurring physical disorders were self-reported. Conclusions: Symptoms of depression may imply varying levels of impairment at different ages. The results suggest a need for age adjustments when estimating the functional impact of depression in the general population. Additionally, they show a need for more accurate assessments of depression-related impairment at older ages. Evidence-based programs may generally benefit from symptom- and age-specific findings.Peer reviewe

Direction of Dependence Between Specific Symptoms of Depression : A Non-Gaussian Approach

Psychopathology could arise from direct interactions between symptoms. Evidence suggests that the mechanisms underlying somatic and cognitive-affective symptoms of depression are different. The aim of this study was to explore dynamic associations among cognitive-affective depression criteria. We used distribution-based direction of dependence models, which estimate whether the presence of symptom A is more likely to depend on the presence of symptom B than vice versa. We analyzed six large samples of adults from the United States (N = 34,963) and conducted a simulation study to test the performance of the algorithm with ordinal variables and a second simulation study focusing on Type I error. Our results were consistent with the literature: Depressed mood and anhedonia were reactive to changes in other symptoms, whereas suicidality may reinforce other symptoms or reflect factors doing so. We discuss the results in the context of other empirical findings and theories of depression, reflect on the potential of these methods in psychopathology, and consider some practical implications.Peer reviewe

Health behaviors and psychological distress : changing associations between 1997 and 2016 in the United States

Objectives Smoking rates have declined with a slower pace among those with psychological distress compared to those without. We examined whether other health behaviors (heavy alcohol consumption, physical inactivity, short sleep duration) showed similar trends associated with sychological distress. We also examined differences by age and birth cohort. Methods Data were from the annually repeated cross-sectional U.S. National Health Interview Surveys (NHIS) of 1997-2016 (total n = 603,518). Psychological distress was assessed with the 6-item Kessler Psychological Distress Scale (K6). Results Psychological distress became more strongly associated with smoking (OR 1.09 per 10 years; 95% CI 1.07, 1.12), physical inactivity (OR 1.08; 1.05, 1.11), and short sleep (OR 1.12; 1.06, 1.18), but less strongly associated with heavy alcohol consumption (OR 0.93; 0.89, 0.98). The associations of smoking and alcohol consumption attenuated with age, whereas the association with physical inactivity strengthened with age. Compared to older birth cohorts, smoking became more strongly associated with psychological distress among younger birth cohorts up to those born in the 1980s. Conclusions The strength of associations between psychological distress and health behaviors may vary by time period, age, and birth cohort.Peer reviewe

Chronic diseases and social risk factors in relation to specific symptoms of depression : Evidence from the U.S. national health and nutrition examination surveys

Background: Depression is a heterogeneous mental disorder with multiple symptoms, but only few studies have examined whether associations of risk factors with depression are symptom-specific. We examined whether chronic diseases and social risk factors (poverty, divorce, and perceived lack of emotional support) are differently associated with somatic and cognitive/affective symptoms of depression. Methods: Cross-sectional analyses were based on individual-level data from the 31,191 participants of six cross-sectional U.S. National Health and Nutrition Examination Surveys (NHANES) carried out between 2005 and 2016. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire. Information on chronic diseases and social risk factors was self-reported by participants. Results: After adjustment for sex, age, race/ethnicity, and all the of other symptoms besides the outcome symptom, higher number of chronic diseases was independently related to fatigue, psychomotor retardation/agitation, and sleep problems in a dose-response pattern (range of odds ratios: 1.21 to 2.59). Except for concentration problems, social risk factors were associated with almost all of the cognitive/affective symptoms (range of odds ratios: 1.02 to 2.09) but only sporadically with somatic symptoms. Limitations: All measures were self-reported by the participants, which may have introduced bias to the associations. Cross-sectional data did not allow us to study temporal dynamics. Conclusions: Specific symptoms of depression may be useful in characterizing the heterogeneous etiology of depression with respect to somatic versus social risk factors.Peer reviewe

Building social capital in a new home country. A closer look into the predictors of bonding and bridging relationships of migrant populations at different education levels

This paper explores factors that may facilitate or hinder the development of migrant populations’ social capital in a settlement country. As earlier research has shown that higher educated migrants tend to form more extensive social relationships, we explore whether there are differences between tertiary educated migrants and those with lower education levels in terms of the background characteristics that predict their social capital composition. The study builds on Robert Putnam’s dyad of bonding and bridging social capital, which are here combined into a single dependent variable. Multinomial regression analyses are done separately for the two education groups. Our data comes from the Survey on Well-Being among Foreign Born Population in Finland (n: of 5,247). The study finds important differences between the education groups both in terms of social capital composition and the respective predictors. Among those with higher education, abundant social capital (i.e. extensive bonding and bridging relationships) is the most common composition, while in the lower education group, the proportion of people with scarce social capital (limited bonding and bridging relationships) outnumbers those with abundant capital by more than twofold. Both education groups draw from similar resources to build abundant social capital, a satisfactory level of income emerging as the single most important underlying factor. However, a satisfactory income level is by far a more common feature in the higher education group. Additionally, the higher education group draws from a more diverse set of other migration and context-related factors to prevent scarce or one-sided social capital.</p

Alcohol abuse predictors in adults with a stable partner

Introducción. El abuso de alcohol es considerado como un problema de salud pública, socialmente generalizado y normalizado. Contribuye a más de 60 enfermedades y problemas sociales, violencia familiar, problemas de pareja y económicos, comportamiento impulsivo, accidentes automovilísticos y una menor productividad laboral. Objetivo. Encontrar el valor predictivo de las variables psicológicas de búsqueda de sensaciones, resiliencia, funcionalidad de pareja y autoeficacia laboral sobre el consumo de alcohol. Método. De corte cuantitativo y alcance explicativo, en el estudio se aplicó en línea una batería de pruebas validada a 249 personas adultas en un rango de edad entre 21 y 65 años (M = 46.7; DT = 11.0) de población mexicana entre 21 y 65 años con pareja y empleo estables. Resultados. Se encontró que las variables de búsqueda de sensaciones y funcionalidad de pareja son las que tienen un mayor valor predictivo en el consumo de alcohol. Un aporte importante de este estudio es el hallazgo de que la funcionalidad de pareja funciona como factor protector del consumo de alcohol aún y cuando alguna de las dos personas de la relación presente búsqueda de sensaciones alta. Conclusiones. Es importante considerarlo en programas de intervención individual, de parejas, en pláticas prematrimoniales y estudios de caso.Introduction. Alcohol abuse is considered a public health problem, socially widespread, and normalized. It can contribute to more than 60 diseases and social problems, family violence, relationship, and financial problems, impulsive behavior, car accidents, and a lower work productivity. Objective. To find the predictive value of psychological variables of sensation seeking, resilience, partner functionality, and work self-efficacy on alcohol consumption. A quantitative explanatory research was conducted. Method. An online survey using validated scales in the Mexican population was applied to 249 Mexican adult people in an age range between 21 and 65 years (M = 1.63; SD = 0.48) with a partner and stable employment. Results. We found that sensation seeking, and partner functionality have the highest predictive value in alcohol consumption. An important contribution of this study is the finding that the couple’s functionality of the couple’s functionality works as a protective factor of alcohol consumption even when one of the two partners in the relationship presents high sensation seeking. Conclusions. This must be considered in intervention programs with individuals, couples, premarital dialogues, and case studies

Programa SALUD 5-10: Programa para el tratamiento del sobrepeso y la obesidad en niños de 5 a 10 años: Antecedentes, Diseño y Metodología

Obesity is a particularly expensive and costly in economic and social terms disease for both people who suffer as public health institutions. Therefore, in recent decades, various international and national organizations have shown great concern for its implications, going to be treated as a real social problem. According to the World Health Organization, Spain is one of the EU countries with the highest prevalence of overweight children as recorded by 33% in the population between 5 and 17 years, whereas in Europe one in four children has overweight or obese. Furthermore, Spain is one of the countries where this disease has grown (in the eighties the prevalence was 15%).&nbsp;Several systematic reviews assessing the effectiveness of intervention programs based on increasing physical activity and dietary control of overweight and / or obesity in children and adolescents highlight the need to design specific programs for schoolchildren, and to assess objectively the effectiveness of such long-term programs in children and adolescents are overweight or obese.&nbsp;The aim of this paper is to describe the design and methodology used in 5-10 Health Program, a program that has been designed with the objective of addressing overweight and obesity in schoolchildren in the age group between 5-10 years.La obesidad es una enfermedad especialmente cara y costosa en términos económicos y sociales tanto para las personas que la padecen como para las instituciones públicas sanitarias. Por ello, en las últimas décadas distintas organizaciones internacionales y nacionales han mostrado una enorme preocupación por sus implicaciones, pasando a ser tratado como un verdadero problema social. Según la Organización Mundial de la Salud, España es uno de los países de la Unión Europea con mayor prevalencia de sobrepeso infantil, ya que registra un 33% en la población entre 5 y 17 años, mientras que en Europa uno de cada cuatro niños tiene sobrepeso o es obeso. Además, España es uno de los países donde más ha crecido esta enfermedad (en la década de los ochenta la prevalencia era de un 15%). Diversas revisiones sistemáticas que evalúan la efectividad de los programas de intervención basados en el aumento de la actividad física y el control dietético sobre el sobrepeso y/u obesidad en población infantil y adolescente resaltan la necesidad de diseñar programas específicos para los escolares, así como valorar objetivamente la eficacia de dichos programas a largo plazo en niños y adolescentes con sobrepeso u obesidad. El objetivo del presente trabajo es describir el diseño y metodología utilizada en el Programa SALUD 5-10, un programa que ha sido diseñado con el objetivo de abordar el sobrepeso y la obesidad en escolares de una franja de edad entre 5 a 10 años

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field