BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 x 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 x 10(-9)). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

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.

Background: Emotional eating (i.e. eating in response to negative emotions) has been suggested to be one mechanism linking depression and subsequent development of obesity. However, studies have rarely examined this mediation effect in a prospective setting and its dependence on other factors linked to stress and its management. We used a population-based prospective cohort of adults and aimed to examine 1) whether emotional eating mediated the associations between depression and 7-year change in body mass index (BMI) and waist circumference (WC), and 2) whether gender, age, night sleep duration or physical activity moderated these associations. Methods: Participants were Finnish 25- to 74-year-olds who attended the DILGOM study at baseline in 2007 and follow-up in 2014. At baseline (n = 5024), height, weight and WC were measured in a health examination. At follow-up (n = 3735), height, weight and WC were based on measured or self-reported information. Depression (Center for Epidemiological Studies - Depression Scale), emotional eating (Three-Factor Eating Questionnaire-R18), physical activity and night sleep duration were self-reported. Age- and gender-adjusted structural equation models with full information maximum likelihood estimator were used in the analyses. Results: Depression and emotional eating were positively associated and they both predicted higher 7-year increase in BMI (R-2 = 0.048) and WC (R-2 = 0.045). The effects of depression on change in BMI and WC were mediated by emotional eating. Night sleep duration moderated the associations of emotional eating, while age moderated the associations of depression. More specifically, emotional eating predicted higher BMI (P = 0.007 for the interaction) and WC (P = 0.026, respectively) gain in shorter sleepers (7 h or less), but not in longer sleepers (9 h or more). Depression predicted higher BMI (P <0.001 for the interaction) and WC (P = 0.065, respectively) increase in younger participants, but not in older participants. Conclusions: Our findings offer support for the hypothesis that emotional eating is one behavioural mechanism between depression and development of obesity and abdominal obesity. Moreover, adults with a combination of shorter night sleep duration and higher emotional eating may be particularly vulnerable to weight gain. Future research should examine the clinical significance of our observations by tailoring weight management programs according to these characteristics.

Depression has been suggested to hinder smoking cessation, especially when co-occurring with nicotine dependence. The study aimed to examine the longitudinal association of depressive symptoms with smoking cessation among daily smokers. The study utilized adult Finnish twin cohort where 1,438 daily smokers (mean age: 38.3, range: 33-45) in 1990 were re-examined for their smoking status in 2011. We assessed baseline depressive symptoms with the Beck Depression Inventory, and the self-reported smoking status at follow-up. The methods included multinomial logistic regression and time to event analyses, adjusted for multiple covariates (age, sex, marital status, social class, heavy drinking occasions, and health status) and smoking heaviness at baseline assessed by cigarettes per day (CPD). Additionally, within-twin-pair analyses were conducted. Results indicated that moderate/severe depressive symptoms at baseline were associated with a lower likelihood of smoking cessation two decades later. Adjusting for covariates, those with moderate/severe depressive symptoms (vs. no/minimal depressive symptoms) had 46% lower likelihood of quitting (relative risk ratio, RRR=0.54, 95% CI: 0.30-0.96). After including CPD, the association of depressive symptoms with smoking cessation attenuated modestly (RRR=0.62, 95% CI: 0.34-1.12). Further, time to event analysis for quitting year since baseline yielded similar findings. In the within-pair analysis, depressive symptoms were not associated with quitting smoking. The results suggest that reporting more depressive symptoms is associated with a lower likelihood of smoking cessation during a 20-year period. The baseline amount of smoking and familial factors partly explain the observed association. Smoking cessation programs should monitor depressive symptoms.

Type 2 diabetes (T2D) has been associated with depressive symptoms, but the causal direction of this association and the underlying mechanisms, such as increased glucose levels, remain unclear. We used instrumental-variable regression with a genetic instrument (Mendelian randomization) to examine a causal role of increased glucose concentrations in the development of depressive symptoms. Data were from the population-based Cardiovascular Risk in Young Finns Study (n = 1217). Depressive symptoms were assessed in 2012 using a modified Beck Depression Inventory (BDI-I). Fasting glucose was measured concurrently with depressive symptoms. A genetic risk score for fasting glucose (with 35 single nucleotide polymorphisms) was used as an instrumental variable for glucose. Glucose was not associated with depressive symptoms in the standard linear regression (B = -0.04, 95% CI [-0.12, 0.04], p = .34), but the instrumental-variable regression showed an inverse association between glucose and depressive symptoms (B = -0.43, 95% CI [-0.79, -0.07], p = .020). The difference between the estimates of standard linear regression and instrumental-variable regression was significant (p = .026) Our results suggest that the association between T2D and depressive symptoms is unlikely to be caused by increased glucose concentrations. It seems possible that T2D might be linked to depressive symptoms due to low glucose levels.

Whether infant regulatory behavior problems already in the first month of life indicate an increased risk of childhood neurobehavioral problems, and whether maternal depression in the postpartum and early childhood underpins these associations remain unclear. Altogether, 2049-2364 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Neonatal Perception Inventory on regulatory behavior problems at the infant's age of 15.6 days (SD 3.2, range 1-30), the Infant Behavior Questionnaire-Revised on temperament at 6.5 months (SD 0.9, range 4.2-12.4), and the Ages and Stages Questionnaire-3 on developmental milestones and the Child Behavior Checklist on behavioral problems at 3.5 years (SD 0.7, range 1.9-6.0). Maternal depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale (infancy follow-ups) and Beck Depression Inventory-II (childhood follow-up). Father-rated infant temperament and paternal depressive symptoms were also available (n = 1474). Higher levels of infant regulatory behavior problems predicted higher levels of mother- and father-rated negative affectivity temperament (0.13 SD units per SD unit, 95% confidence interval 0.09-0.17; and 0.09, 0.04-0.14, respectively), lower levels of mother-rated orienting/regulation temperament (- 0.09, - 0.13 to - 0.05) and problem-solving skills (- 0.12, - 0.21 to - 0.04), and higher levels of Externalizing (0.07, 0.03-0.11) and Total behavioral problems (0.07, 0.03-0.11). Regulatory behaviors partially mediated the effect of maternal depressive symptoms. Regulatory behavior problems already during the first month of life predict neurobehavioral outcomes, and partially mediate the effect of maternal depressive symptoms. Our study may inform design of interventions aimed at timely prevention in children at risk.

Depression is a psychiatric disorder composed of several clusters of symptoms, which do not necessarily reflect common pathways of pathophysiological processes. Thus, a new conceptualization of depression has been proposed, which suggests that depression should be dissected to its key components instead of treating it as one homogeneous concept. Personality trait neuroticism is a risk factor that is consistently linked with depression. Several models have been suggested for the association between neuroticism and depression. One of them is a so-called common cause -model, which assumes that a shared etiology explains the co-occurrence of the two. Research from twin studies supports this notion, as neuroticism and depression have been found to share a large proportion of their genetic basis. However, earlier research has examined depression as a composite concept, and there are no studies to date which would have examined the shared genetic basis of specific symptoms of depression in relation with neuroticism. This study tests the common cause -model by estimating, whether the same genetic and environmental components are relevant in explaining the covariation between neuroticism and specific symptoms of depression. The data used in this study was from the Swedish Adoption/Twin Study (n = 1515, av. age = 62.0). Depression was measured with The Center for Epidemiological Studies - Depression Scale (CES-D), and separate analyses were conducted for three factors: somatic complaints, (lack of) positive affect and depressed affect. The results showed that all of the depressive symptoms shared the same genetic and environmental components when modeling the association with neuroticism, which supports the common cause -model. Over a half of the phenotypic correlation was explained by genetic influences between neuroticism and somatic complaints, as well as neuroticism and positive affect. Half of the co-variation between neuroticism and depressed affect was due to genetic influences. Findings of the current study suggest, that genetic and individual specific environmental influences are important in explaining the relationship in all of the symptoms. For future endeavors, it is suggested to search for concrete risk factors and neurobiological endophenotypes that are shared between specific symptoms and neuroticism. While the use of composite concept of depression was supported in this study, the research question has not been yet examined in molecular genetic studies. A twin model can only differentiate sources of variation, not concrete risk factors. Thus, the results presented here only apply in the context of twin modeling. Also, the robustness of the results should be tested by replicating the results among younger samples.

Objectives To assess the associations of perceived financial satisfaction and health-related quality of life (HRQoL) and depressive symptoms in an unselected pregnant population in early pregnancy. Methods 750 consecutive pregnant women attending the first communal ultrasound examination before gestational week 14 were invited to participate. Questionnaires assessing HRQoL (15D), depressive symptoms (Edinburgh Depression Scale, EPDS), medical, obstetric, and socioeconomic status were handed out. The participants were divided into three groups according to their satisfaction with their financial status, (unsatisfied, somewhat satisfied, and satisfied). Main outcome measures were 15D and EPDS-scores and dimensions of HRQoL. Results 325 (43,3%) questionnaires were returned. The mean 15D-score for HRQoL was 0,926 (SD 0,056). The financially unsatisfied women had lower HRQoL than women in more satisfied groups (0.906, 0.923 and 0.931, p = 0.012). The result remained significant, even after adjusting for age and education(p = 0.032). The unsatisfied women had a higher mean body mass index (BMI) (25.4, 24.4 and 23.2 kg/m(2), p for linearity = 0.002), were more often smokers, (13 vs. 4 and 3%, p = 0.029), and had experienced at least one abortion (18, 14 and 7%, p = 0.017). Dimensions of depression, distress and sleep explained the differences between the groups. 27% of unsatisfied women scored EPDS ae10 points suggesting increased risk of depression. Conclusions Financial satisfaction in early pregnancy associates with HRQoL and risk of perinatal depressive symptoms. Unsatisfied women more often have risk factors for unfavourable pregnancy outcomes which may influence the later health and wellbeing of the mother and child.

Purpose To examine the relationship between leisure-time physical activity (LTPA) and ability to meet different work requirements among adult working men with or without current depressive symptoms. Methods We measured LTPA with the long version of the International Physical Activity Questionnaire (IPAQ). The Work Ability Index (WAI) and Beck Depression Inventory (BDI) were used to assess the work ability and depression of 921 Finnish employed male volunteers. Participants were divided into three groups according to the WAI for their work requirements: mental (MENT), physical (PHYS), and an equal amount of mental and physical work (BTH). Results When adjusted for age, BMI and employment years, there was a significant difference in weekly LTPA between WAI groups {p = 0.003, [F (2902) = 5.58]}, but not for depression. It appeared that participants with depressive symptoms scored lower WAI in each group regardless of LTPA. In addition, a linear relationship was found between higher LTPA and WAI in nondepressed workers in the PHYS [p = 0.011, beta = 0.10 (95% CI 0.03-0.18)] and BTH [p = 0.027, beta = 0.19 (95% CI 0.03-0.34)] groups. Among workers with depressive symptoms, similar linearity was found in BTH [p = 0.003, beta = 0.20 (95% CI 0.03-0.55)]. In group-wise comparison, work requirements {p = 0.001, [F (2902) = 11.2]} and depressive symptoms {p <0.001, [F (1902) = 177.0]} related with lower WAI. Conclusion Depressive symptoms were associated with lower work ability regardless of the job description. Therefore, higher levels of weekly LTPA was linked with better work ability among nondepressed working men. Workers with depressive symptoms in jobs that require extensive mental or physical work might need more than exercise to improve work ability.

Objective: This follow-up study aimed to evaluate risk factors for menopausal sleep disturbances already identifiable before menopause. Methods: At baseline, all 81 women were premenopausal. At year-five follow-up, 27 of the women were premenopausal, 40 postmenopausal, and 14 postmenopausal and using hormone therapy. We used the Basic Nordic Sleep Questionnaire to study sleep; additional questionnaires evaluated risk factors for sleep impairment. Results: Sleep quality differed only marginally between the groups. The following baseline variables were associated with impaired sleep quality at follow-up: depressive symptoms increased the risk of nocturnal awakenings (OR 1.16 (95%CI 1.02-1.32), p = 0.025), morning tiredness (OR 1.22 (95%CI 1.06-1.40), p = 0.007), daytime tiredness (OR 1.24 (95%CI 1.06-1.44), p = 0.007) and propensity to fall asleep during work or leisure time (OR 1.18 (95%CI 1.01-1.37), p = 0.036). Personal crises increased the risk of longer sleep latency (OR 5.46 (95%CI 1.13-26.32), p = 0.035) and of propensity to fall asleep when not active (OR 5.41 (95%CI 1.42-20.83), p = 0.014). Use of medications affecting the CNS increased the risk of worse general sleep quality (OR 11.44 (95% CI 1.07-121.79), p = 0.044). Perceived impaired general health (OR 2.87 (95%CI 1.04-7.94), p = 0.043) and frequent night sweats (OR 10.50 (95%CI 2.25-49.01), p = 0.003) increased the risk of difficulty falling asleep. Conclusions: Various premenopausal health-related factors seem to predict poor sleep in menopausal transition. Menopause itself appears to have only minor effects. Thus, it is essential to identify high risk women to allow timely interventions that may prevent the development of sleep disturbances at menopause. (C) 2016 Elsevier Ireland Ltd. All rights reserved.