The risk relationships between alcohol consumption, alcohol use disorder and alcohol use disorder mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim was to estimate the risk relationships between alcohol consumption and AUD incidence and mortality. METHOD: A systematic literature search was conducted, using Medline, Embase, PsycINFO and Web of Science for case-control or cohort studies published between 1 January 2000 and 8 July 2022. These were required to report alcohol consumption, AUD incidence and/or AUD mortality (including 100% alcohol-attributable deaths). The protocol was registered with PROSPERO (CRD42022343201). Dose-response and random-effects meta-analyses were used to determine the risk relationships between alcohol consumption and AUD incidence and mortality and mortality rates in AUD patients, respectively. RESULTS: Of the 5904 reports identified, seven and three studies from high-income countries and Brazil met the inclusion criteria for quantitative and qualitative syntheses, respectively. In addition, two primary US data sources were analyzed. Higher levels of alcohol consumption increased the risk of developing or dying from an AUD exponentially. At an average consumption of four standard drinks (assuming 10 g of pure alcohol/standard drink) per day, the risk of developing an AUD was increased sevenfold [relative risk (RR) = 7.14, 95% confidence interval (CI) = 5.13-9.93] and the risk of dying fourfold (RR = 3.94, 95% CI = 3.53-4.40) compared with current non-drinkers. The mortality rate in AUD patients was 3.13 (95% CI = 1.07-9.13) per 1000 person-years. CONCLUSIONS: There are exponential positive risk relationships between alcohol use and both alcohol use disorder incidence and mortality. Even at an average consumption of 20 g/day (about one large beer), the risk of developing an alcohol use disorder (AUD) is nearly threefold that of current non-drinkers and the risk of dying from an AUD is approximately double that of current non-drinkers.

Sex-Specific Association of Alcohol Use Disorder With Suicide Mortality: A Systematic Review and Meta-Analysis.

Importance: Despite individual studies suggesting that sex differences exist in the association between alcohol use disorder (AUD) and suicide, most existing systematic reviews and meta-analyses have reported associations across the sexes. Objective: To estimate the sex-specific association between AUD and suicide mortality. Data Sources: Embase, MEDLINE (including MEDLINE In-Process), PsycINFO, PubMed, and Web of Science were searched from database inception to April 27, 2022. Study Selection: Inclusion criteria consisted of the following: (1) original, quantitative study, (2) inclusion of a measure of association and its corresponding measure of variability (or sufficient data to calculate these [eg, 95% CI]), and (3) results stratified by sex. Data Extraction and Synthesis: Data extraction was completed by one reviewer and then cross-checked by a second reviewer. Risk of bias was assessed by study design. Categorical random-effects meta-analyses were conducted to obtain sex-specific pooled estimates of the association between AUD and suicide mortality risk. Methodological moderators (ie, study design and comparator group) were assessed using sex-stratified meta-regressions. Main Outcomes and Measures: The association between AUD and suicide mortality. Results: A total of 16 347 unique records were identified in the systematic search; 24 studies were ultimately included for 37 870 699 participants (59.7% male and 40.3% female) (23 risk estimates for male and 17 for female participants). Participants ranged in age from 15 years to 65 years or older. Sex-specific meta-regression models indicated that study design (ie, longitudinal vs cross-sectional study design) affected the observed association between AUD and suicide mortality for both male participants (log odds ratio, 0.68 [95% CI, 0.08-1.28]; P = .03) and female participants (log odds ratio, 1.41 [95% CI, 0.57-2.24]; P < .001). For males and females, among longitudinal studies, the pooled odds ratios were 2.68 (95% CI, 1.86-3.87; I2 = 99% [n = 14]) and 2.39 (95% CI, 1.50-3.81; I2 = 90% [n = 11]), respectively. Conclusions and Relevance: This systematic review and meta-analysis yielded substantive evidence that AUD was associated with suicide mortality and that the association was similar across the sexes. The findings underscore the importance of identifying and treating AUD as part of a comprehensive suicide prevention strategy.

Alcoholic beverage types consumed by population subgroups in the United States: Implications for alcohol policy to address health disparities.

INTRODUCTION: We aimed to identify alcoholic beverage types more likely to be consumed by demographic subgroups with greater alcohol-related health risk than others, mainly individuals with low socio-economic status, racial/ethnic minority status and high drinking levels. METHODS: Fractional logit modelling was performed using a nationally representative sample of US adult drinkers (analytic N = 37,657) from the National Epidemiologic Survey on Alcohol and Related Conditions Waves 2 (2004-2005) and 3 (2012-2013). The outcomes were the proportions of pure alcohol consumed as beer, wine, liquor and coolers (defined as wine-/malt-/liquor-based coolers, hard lemonade, hard cider and any prepackaged cocktails of alcohol and mixer). RESULTS: Adults with lower education and low or medium income were more likely to drink beer, liquor and coolers, while those with a 4-year college/advanced degree and those with high income preferred wine. Excepting Asian adults, racial/ethnic minority adults were more likely to drink beer (Hispanics) and liquor (Blacks), compared with White adults. High- or very-high-level drinkers were more likely to consume liquor and beer and less likely to consume wine (and coolers), compared with low-level drinkers. High-level and very-high-level drinkers, who were less than 10% of all drinkers, consumed over half of the total volume of beer, liquor and coolers consumed by all adults. DISCUSSION AND CONCLUSIONS: Individuals with low socio-economic status, racial/ethnic minority status or high drinking level prefer liquor and beer. As alcohol taxes, sales and marketing practices all are beverage-specific, targeted approaches to reduce consumption of these beverages, particularly among individuals with these profiles, are warranted.

How does alcohol use impact morbidity and mortality of liver cirrhosis? A systematic review and dose-response meta-analysis.

BACKGROUND: Alcohol consumption is the most important risk factor responsible for the disease burden of liver cirrhosis (LC). Estimates of risk relationships available usually neither distinguish between different causes such as alcohol-related LC or hepatitis-related LC, nor differentiate between morbidity and mortality as outcome. We aimed to address this research gap and identify dose-response relationships between alcohol consumption and LC, by cause and outcome. METHODS: A systematic review using PubMed/Medline and Embase was conducted, identifying studies that reported an association between level of alcohol use and LC. Meta-regression models were used to estimate the dose-response relationships and control for heterogeneity. RESULTS: Totally, 44 studies, and 1 secondary data source, with a total of 5,122,534 participants and 15,150 cases were included. Non-linear dose-response relationships were identified, attenuated for higher levels of consumption. For morbidity, drinking 25 g/day was associated with a RR of 1.81 (95% CI 1.68-1.94) compared to lifetime abstention; 50 g/day and 100 g/day corresponded to 3.54 (95% CI 3.29-3.81) and 8.15 (95% CI 7.46-8.91), respectively. For mortality, for 25 g/day, a RR of 2.65 (95% CI 2.22-3.16); for 50 g/day, a RR of 6.83 (95% CI 5.84-7.97); for 100 g/day, a RR of 16.38 (95% CI 13.81-19.42) were identified. A higher risk for alcohol-related and all-cause LC as compared to hepatitis C-related LC was found. CONCLUSION: Our results demonstrated higher acceleration for mortality compared to morbidity. The current findings will inform the way we quantify the burden due to LC attributable to alcohol use.

The Relationship Between Alcohol Consumption, BMI, and Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: Moderate alcohol use may be associated with lower risk of type 2 diabetes mellitus (T2DM). Previous reviews have reached mixed conclusions. PURPOSE: To quantify the dose-response relationship between alcohol consumption and T2DM, accounting for differential effects by sex and BMI. DATA SOURCES: Medline, Embase, Web of Science, and one secondary data source. STUDY SELECTION: Cohort studies on the relationship between alcohol use and T2DM. DATA EXTRACTION: Fifty-five studies, and one secondary data source, were included with a combined sample size of 1,363,355 men and 1,290,628 women, with 89,983 and 57,974 individuals, respectively, diagnosed with T2DM. DATA SYNTHESIS: Multivariate dose-response meta-analytic random-effect models were used. For women, a J-shaped relationship was found with a maximum risk reduction of 31% (relative risk [RR] 0.69, 95% CI 0.64-0.74) at an intake of 16 g of pure alcohol per day compared with lifetime abstainers. The protective association ceased above 49 g per day (RR 0.82, 95% CI 0.68-0.99). For men, no statistically significant relationship was identified. When results were stratified by BMI, the protective association was only found in overweight and obese women. LIMITATIONS: Our analysis relied on aggregate data. We included some articles that determined exposure and cases via self-report, and the studies did not account for temporal variations in alcohol use. CONCLUSIONS: The observed reduced risk seems to be specific to women in general and women with a BMI ≥25 kg/m2. Our findings allow for a more precise prediction of the sex-specific relationship between T2DM and alcohol use, as our results differ from those of previous studies.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

BACKGROUND: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. METHODS: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical activity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. RESULTS: 465,073 adults (18-85 years) were followed 8.9 years (SD: 5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to the lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. CONCLUSIONS: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and to advance health equity.

Reducing alcohol use through alcohol control policies in the general population and population subgroups: a systematic review and meta-analysis.

We estimate the effects of alcohol taxation, minimum unit pricing (MUP), and restricted temporal availability on overall alcohol consumption and review their differential impact across sociodemographic groups. Web of Science, Medline, PsycInfo, Embase, and EconLit were searched on 08/12/2022 and 09/26/2022 for studies on newly introduced or changed alcohol policies published between 2000 and 2022 (Prospero registration: CRD42022339791). We combined data using random-effects meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1887 reports, 36 were eligible. Doubling alcohol taxes or introducing MUP (Int$ 0.90/10 g of pure alcohol) reduced consumption by 10% (for taxation: 95% prediction intervals [PI]: -18.5%, -1.2%; for MUP: 95% PI: -28.2%, 5.8%), restricting alcohol sales by one day a week reduced consumption by 3.6% (95% PI: -7.2%, -0.1%). Substantial between-study heterogeneity contributes to high levels of uncertainty and must be considered in interpretation. Pricing policies resulted in greater consumption changes among low-income alcohol users, while results were inconclusive for other socioeconomic indicators, gender, and racial and ethnic groups. Research is needed on the differential impact of alcohol policies, particularly for groups bearing a disproportionate alcohol-attributable health burden. Funding: Research reported in this publication was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA028009.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

Background: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. Methods: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical inactivity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. Results: 465,073 adults (18-85 years) were followed 8.9 years (SD:5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to these lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. Conclusions: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and advance health equity.

Simulation of Alcohol Control Policies for Health Equity (SIMAH) Project: Study Design and First Results.

Since about 2010, life expectancy at birth in the United States has stagnated and begun to decline, with concurrent increases in the socioeconomic divide in life expectancy. The Simulation of Alcohol Control Policies for Health Equity (SIMAH) Project uses a novel microsimulation approach to investigate the extent to which alcohol use, socioeconomic status (SES), and race/ethnicity contribute to unequal developments in US life expectancy and how alcohol control interventions could reduce such inequalities. Representative, secondary data from several sources will be integrated into one coherent, dynamic microsimulation to model life-course changes in SES and alcohol use and cause-specific mortality attributable to alcohol use by SES, race/ethnicity, age, and sex. Markov models will be used to inform transition intensities between levels of SES and drinking patterns. The model will be used to compare a baseline scenario with multiple counterfactual intervention scenarios. The preliminary results indicate that the crucial microsimulation component provides a good fit to observed demographic changes in the population, providing a robust baseline model for further simulation work. By demonstrating the feasibility of this novel approach, the SIMAH Project promises to offer superior integration of relevant empirical evidence to inform public health policy for a more equitable future.

Behavioral stability of alcohol consumption and socio-demographic correlates of change among a nationally representative cohort of US adults.

AIMS: To estimate the probability of transitioning between different categories of alcohol use (drinking states) among a nationally representative cohort of United States (US) adults and to identify the effects of socio-demographic characteristics on those transitions. DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a prospective cohort study conducted in 2001-02 and 2004-05; a US nation-wide, population-based study. Participants included 34 165 adults (mean age = 45.1 years, standard deviation = 17.3; 52% women). MEASUREMENTS: Alcohol use was self-reported and categorized based on the grams consumed per day: (1) non-drinker (no drinks in past 12 months), (2) category I (women = ≤ 20; men = ≤ 40), (3) category II (women = 21-40; men = 41-60) and (4) category III (women = ≥ 41; men = ≥ 61). Multi-state Markov models estimated the probability of transitioning between drinking states, conditioned on age, sex, race/ethnicity and educational attainment. Analyses were repeated with alcohol use categorized based on the frequency of heavy episodic drinking. FINDINGS: The highest transition probabilities were observed for staying in the same state; after 1 year, the probability of remaining in the same state was 90.1% [95% confidence interval (CI) = 89.7%, 90.5%] for non-drinkers, 90.2% (95% CI = 89.9%, 90.5%) for category I, 31.8% (95% CI = 29.7, 33.9%) category II and 52.2% (95% CI = 46.0, 58.5%) for category III. Women, older adults, and non-Hispanic Other adults were less likely to transition between drinking states, including transitions to lower use. Adults with lower educational attainment were more likely to transition between drinking states; however, they were also less likely to transition out of the 'weekly HED' category. Black adults were more likely to transition into or stay in higher use categories, whereas Hispanic/Latinx adults were largely similar to White adults. CONCLUSIONS: In this study of alcohol transition probabilities, some demographic subgroups appeared more likely to transition into or persist in higher alcohol consumption states.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Educational Attainment and Lifestyle Risk Factors Associated With All-Cause Mortality in the US.

IMPORTANCE: The US has experienced increasing socioeconomic inequalities and stagnating life expectancy. Past studies have not disentangled 2 mechanisms thought to underlie socioeconomic inequalities in health, differential exposure and differential vulnerability, that have different policy implications. OBJECTIVE: To evaluate the extent to which the association between socioeconomic status (SES) and all-cause mortality can be decomposed into a direct effect of SES, indirect effects through lifestyle factors (differential exposure), and joint effects of SES with lifestyle factors (differential vulnerability). DESIGN SETTING AND PARTICIPANTS: This nationwide, population-based cohort study used the cross-sectional US National Health Interview Survey linked to the National Death Index. Civilian, noninstitutionalized US adults aged 25 to 84 years were included from the 1997 to 2014 National Health Interview Survey and were followed up until December 31, 2015. Data were analyzed from May 1 to October 31, 2021. A causal mediation model using an additive hazard and marginal structural approach was used. EXPOSURES: Both SES (operationalized as educational attainment) and lifestyle risk factors (smoking, alcohol use, obesity, and physical inactivity) were assessed using self-reported questionnaires. MAIN OUTCOMES AND MEASURES: Time to all-cause mortality. RESULTS: Participants included 415 764 adults (mean [SD] age, 49.4 [15.8] years; 55% women; 64% non-Hispanic White), of whom 45% had low educational attainment and 27% had high educational attainment. Participants were followed up for a mean (SD) of 8.8 (5.2) years during which 49 096 deaths (12%) were observed. Low educational attainment (compared with high) was associated with 83.6 (men; 95% CI, 81.8-85.5) and 54.8 (women; 95% CI, 53.4-56.2) additional deaths per 10 000 person-years, of which 66% (men) and 80% (women) were explained by lifestyle factors. Inequalities in mortality were primarily a result of greater exposure and clustering of unhealthy lifestyle factors among low SES groups; with some exceptions among women, little evidence of differential vulnerability was identified. CONCLUSIONS AND RELEVANCE: In this cohort study, differential exposure to lifestyle risk factors was an important mediator of socioeconomic inequalities in mortality. Public health interventions are needed, particularly among low SES groups, to address smoking, physical inactivity, alcohol use, and the socioenvironmental contexts within which these risk factors develop.

Socioeconomic status, alcohol use disorders, and depression: A population-based study.

BACKGROUND: Depressive disorders (DD) and alcohol use disorders (AUD) frequently co-occur. They are key to understanding the current increases in "deaths of despair" among individuals with lower socioeconomic status (SES). The aim of this study was to assess the prospective bidirectional associations between AUD and DD, as well as the effect of SES on these two conditions. METHODS: The National Epidemiologic Survey on Alcohol and Related Conditions is a cohort study representative of the US adult population, which began in 2001-2002, with follow-up interviews conducted 3 years later. SES was primarily operationalized as educational attainment. AUD, DD, and their levels of severity were defined according to the DSM-5 criteria. RESULTS: The risk of developing an incident DD increased gradually with the recency and the severity of AUD at baseline, but the converse was not observed. Lower SES was an independent risk for incident AUD or DD. SES did not modify the prospective association between AUD and DD. LIMITATIONS: The absence of interaction between SES and moderate or severe AUD for the incident DD must be considered with caution due to the limited number of DD cases reported in these AUD categories. CONCLUSIONS: This result is consistent with a causal relationship between AUD and DD, and suggests that therapeutic interventions for AUD may also have beneficial effects to lower DD rates. The independent effects of a lower SES and AUD on DD may result in a vulnerable population cumulating disorders with heavy consequences on health and social well-being.

Sex-specific association between alcohol consumption and liver cirrhosis: An updated systematic review and meta-analysis.

Different studies have shown that females develop liver diseases at lower levels of alcohol consumption than males. Our aim was to quantify the dose-response relationship between alcohol consumption and the risk of liver cirrhosis by sex and identify the differences between females and males. A systematic review was conducted using PubMed/Medline and Embase to identify longitudinal and case-control studies that analyzed the relationship between the level of alcohol use and liver cirrhosis (LC) incidence, and mortality (ICD-8 and ICD-9 codes 571 and ICD-10 codes K70, K73, K74). Pooled relative risks (RR) were calculated by random effects models. Restricted cubic splines were used to model the dose-response relationship. A total of 24 studies were included in the analysis. There were collectively 2,112,476 females and 924,853 males, and a total of 4,301 and 4,231 cases of LC for females and males, respectively. We identified a non-linear dose-response relationship. Females showed a higher risk for LC compared to males with the same amount of alcohol consumed daily. For instance, drinking 40 g/day showed RRs of 9.35 (95% CI 7.64-11.45) in females and 2.82 (95% CI 2.53-3.14) in males, while drinking 80 g/day presented RRs of 23.32 (95% CI 18.24-29.82) in females and 7.93 (95% CI 7.12-8.83) in males. Additional analyses showed that a higher risk for females was found for morbidity and for mortality. Understanding the influence of sex on the association of alcohol consumption and the risk of LC is needed to develop recommendations and clinical guidelines for prevention and treatment. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299680, identifier CRD42022299680.

Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations.

BACKGROUND: Only a few studies with conflicting results have examined the effects of sex on the prospective association between depression and subsequent obesity. OBJECTIVE: (1) To simultaneously assess the associations of the subtypes (atypical, melancholic, unspecified) of major depressive disorder (MDD) measured at baseline and subtypes of major depressive episodes (MDE) that emerged during a 5.5-year follow-up with changes in obesity markers (body mass index, waist circumference, fat mass) during this follow-up, and (2) to test the effect of sex on these associations. METHODS: Data from CoLaus|PsyCoLaus, a population-based cohort study including 2702 participants (50.1% women, mean age 49.6 years). Criteria for mental disorders were elicited using semi-structured interviews. RESULTS: History of atypical MDD at baseline was associated with a steeper increase in BMI and waist circumference, whereas atypical MDE during follow-up was associated with a steeper increase in the three studied obesity markers. Melancholic MDD at baseline was associated with a steeper increase in BMI. Several significant interactions with sex were found indicating higher increase in fat mass in men than in women following melancholic MDD reported at baseline, higher decrease in BMI and fat mass in women than in men related to melancholic MDE emerging during follow-up and higher increase in waist circumference in men than in women following unspecified MDD reported at baseline. LIMITATIONS: Urban sample which may not be representative for the whole population. CONCLUSIONS: Our results further advocate for the specific need of a thorough monitoring of obesity markers in patients with atypical MDD and suggest less favorable obesity marker changes mainly related to melancholic MDE in men.

Dietary Patterns are Differentially Associated with Atypical and Melancholic Subtypes of Depression.

Diet has been associated with the risk of depression, whereas different subtypes of depression have been linked with different cardiovascular risk factors (CVRFs). In this study, our aims were to 1) identify dietary patterns with exploratory factor analysis, 2) assess cross-sectional associations between dietary patterns and depression subtypes, and 3) examine the potentially mediating effect of dietary patterns in the associations between CVRFs and depression subtypes. In the first follow-up of the population-based CoLaus|PsyCoLaus study (2009-2013, 3554 participants, 45.6% men, mean age 57.5 years), a food frequency questionnaire assessed dietary intake and a semi-structured interview allowed to characterize major depressive disorder into current or remitted atypical, melancholic, and unspecified subtypes. Three dietary patterns were identified: Western, Mediterranean, and Sweet-Dairy. Western diet was positively associated with current atypical depression, but negatively associated with current and remitted melancholic depression. Sweet-Dairy was positively associated with current melancholic depression. However, these dietary patterns did not mediate the associations between CVRFs and depression subtypes. Hence, although we could show that people with different subtypes of depression make different choices regarding their diet, it is unlikely that these differential dietary choices account for the well-established associations between depression subtypes and CVRFs.

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community.

OBJECTIVE: The complex relationship between psychosocial stress over the lifetime, psychological factors, and cardiometabolic risk is still poorly understood. Accordingly, our aims were (1) to independently assess the associations between childhood adversity, life-event stress in remote (earlier than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to determine the role of psychological factors including personality, coping, and depression in these associations. METHODS: The sample included 2674 adults, aged 35 to 66 years, randomly selected from urban area. Participants underwent a physical examination including the assessment of obesity markers, blood pressure, and blood lipid and glucose levels. Stress during adulthood was determined using the severity scores of 52 stressful life events. Information on adverse childhood experiences and major depressive disorders was collected using semistructured interviews, whereas personality traits and coping mechanisms were evaluated through questionnaires. RESULTS: Both childhood adversity and stress in remote adulthood were associated with elevated body mass index (ß [95% confidence interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist circumference (ß [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and the global cardiometabolic risk score (ß [95% CI] = 0.278 [0.017 to 0.540]; 0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and psychological factors. In addition, childhood adversity was associated with low high density lipoprotein levels (ß [95% CI] = -0.021 [-0.042 to 0.000]), as well as increased fat mass and systolic blood pressure levels (ß [95% CI] = 0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood with apolipoprotein B levels (ß [95% CI] = 0.607 [0.312 to 0.901]). Psychological factors did not account for these associations and were not effect modifiers. CONCLUSIONS: Our data demonstrate that psychosocial stress during childhood and remote adulthood favor adiposity and abnormal lipid metabolism.

The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: Results from a large longitudinal population-based study.

BACKGROUND: Although there has been abundant research on chronic low-grade inflammation as a potential mechanism underlying the link between mood disorders and cardiovascular risk, less is known about the role of inflammatory factors and anxiety disorders. The aim of this paper is to evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP) with anxiety disorders and its subgroups. METHODS: The sample consisted of 3,113 participants (53.7% women; mean age: 51.0, S.D. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, S.D. 0.6). Anxiety disorders were assessed with semistructured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. RESULTS: After adjustment for potential confounders, current anxiety disorders (ß = 0.09, 95% CI 0.00-0.17) and agoraphobia (ß = 0.25, 95% CI: 0.07-0.43) at baseline were associated with a steeper increase of hsCRP levels over the follow-up period. Current posttraumatic stress disorder (PTSD) was associated with a lower increase of IL-6 levels over the follow-up period (ß = -0.52, 95% CI: -1.00/-0.04). There was no evidence for an association between inflammation markers at baseline and anxiety disorders at follow-up. CONCLUSIONS: The prospective association between agoraphobia at baseline and hsCRP levels over the follow-up period suggests that chronic low-grade inflammation may be a consequence of this condition. The decrease in IL-6 in PTSD also requires further investigation. No evidence was found for chronic low-grade inflammation as a predictor of future anxiety disorders.

Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife.

BACKGROUND: Given the well known heterogeneity of Major Depressive Disorder (MDD), dividing this complex disorder into subtypes is likely to be a more promising approach to identify its determinants than to study it as a whole. METHODS: In a prospective population-based cohort study (CoLaus|PsyCoLaus) with 5.5 years of follow-up, 1524 participants without MDD at baseline, aged 35-66 years (mean age 51.4 years, 43.4% females), participated in the physical and psychiatric baseline and the psychiatric follow-up evaluations. RESULTS: The incidence of both atypical and melancholic MDD during the follow-up period were predicted by female sex, a lifetime history of minor depressive disorders and higher neuroticism scores. Higher baseline body mass index was associated with the onset of atypical MDD, whereas the absence of hypertension and younger age were associated with the development of melancholic MDD. Unspecified MDD was predicted by younger age, low concentrations of tumor necrosis factor-α and elevated life-event impact scores. LIMITATIONS: The age range of our cohort restricts the identification of risk factors to MDD with onset in midlife and the recruitment in an urban area limits the generalizability of the findings. CONCLUSIONS: Our data suggest that MDD subtypes are predicted by partially distinct combinations of baseline characteristics suggesting that these subtypes not only differ in their clinical manifestations but also in factors that contribute to their development. Subjects with minor depressive episodes, especially in combination with particular personality features, deserve close clinical attention to prevent the subsequent onset of atypical and melancholic major depression.