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Background There is considerable heterogeneity in antidepressant treatment response across individuals. As people with depression may manifest different symptom profiles, we hypothesized that the constellation of specific depressive symptoms might explain some of the heterogeneity in antidepressant treatment response. To assess this hypothesis, we examined symptom-specific remission related to antidepressant vs placebo treatment among those with and without a treatment response. Methods Data were from 19 randomized controlled trials (n = 7,344). Depressive symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17). Data on treatment were dichotomized into active treatment vs placebo. Treatment response was defined as ≥50% reduction in the HDRS-17 sum score during trial follow-up. Associations of antidepressant treatment with symptom remission were assessed in logistic regression models conducted separately for each symptom, adjusting for age, sex, follow-up time, and the presence of the symptom at baseline. Treatment responders and non-responders were analyzed separately. We also assessed trajectories of symptom remission across the trial follow-up in both treatment conditions among responders and non-responders. Results There were no coherent differences in symptom remission between the antidepressant and placebo conditions either among responders (OR=0.75–1.28) or non-responders (OR=0.49–1.35). Likewise, there were no coherent differences between the remission trajectories either among treatment responders or non-responders. Limitations Treatment responders and non-responders were analyzed separately, which may have introduced bias that could affect the validity of our findings. Conclusions We observed no consistent evidence that treatment response to antidepressants depends on the patient's specific symptom profile.

Background Perceived disease risk may reflect actual risk indicators and/or motivation to change lifestyle. Yet, few longitudinal studies have assessed how perceived risk relates to risk indicators among different disease risk groups. We examined in a 5-year follow-up, whether perceived risks of diabetes and cardiovascular disease predicted physical activity, body mass index (BMI kg/m2), and blood glucose level, or the reverse. We examined further whether perceived risk, self-efficacy, and outcome beliefs together predicted changes in these risk indicators. Method Participants were high diabetes risk participants (N = 432) and low/moderate-risk participants (N = 477) from the national FINRISK 2002 study who were followed up in 2007. Both study phases included questionnaires and health examinations with individual feedback letters. Data were analyzed using gender- and age-adjusted structural equation models. Results In cross-lagged autoregressive models, perceived risks were not found to predict 5-year changes in physical activity, BMI, or 2-h glucose. In contrast, higher BMI and 2-h glucose predicted 5-year increases in perceived risks (β-values 0.07–0.15, P-values β-values 0.10–0.16, P-values 0.005–0.034). Higher outcome beliefs predicted lower BMI among the low/moderate-risk sample (β-values − 0.04 to − 0.05, P-values 0.008–0.011). Conclusion Perceived risk of chronic disease rather follows risk indicators than predicts long-term lifestyle changes. To promote sustained lifestyle changes, future intervention studies need to examine the best ways to combine risk feedback with efficient behavior change techniques.

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish‐conforming pseudo‐words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer's disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants' inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single‐route models) and contradict theories advocating for formal symbolic rules (dual‐route models). While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish-conforming pseudo-words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer’s disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants’ inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single-route models) and contradict theories advocating for formal symbolic rules (dual-route models).

Thirty-nine participants listened to 28 neutral and horror excerpts of Stephen King short stories while constantly tracking their emotional arousal. Pupil size was measured with an Eyelink 1000+, and participants rated valence and transportation after each story. In addition to computing mean pupil size across 1-sec intervals, we extracted blink count and used detrended fluctuation analysis (DFA) to obtain the scaling exponents of long-range temporal correlations (LRTCs) in pupil size time-series. Pupil size was expected to be sensitive also to emotional arousal, whereas blink count and LRTC’s were expected to reflect cognitive engagement. The results showed that self-reported arousal increased, pupil size was overall greater, and the decreasing slope of pupil size was flatter for horror than for neutral stories. Horror stories induced higher transportation than neutral stories. High transportation was associated with a steeper increase in self-reported arousal across time, stronger LRTCs in pupil size fluctuations, and lower blink count. These results indicate that pupil size reflects emotional arousal induced by the text content, while LRTCs and blink count are sensitive to cognitive engagement associated with transportation, irrespective of the text type. The study demonstrates the utility of pupillometric measures and blink count to study literature reception.

Testosterone is one possible biomarker for depression risk among men and women. Both high and low levels of testosterone have been associated with depression, at least among men. Testosterone may be associated only with specific symptoms of depression, which might help to explain inconsistencies in previous results. We examined the cross-sectional associations between total testosterone and the specific symptoms of depression using pooled data across three cycles of NHANES (2011–2012, 2013–2014, and 2015–2016). The sample included 4253 men and 5102 women. Testosterone was modelled as 1) a dichotomous (low testosterone cut-off

Go/No‐Go tasks, which require participants to inhibit automatic responses to images of palatable foods, have shown diagnostic value in quantifying food‐related impulses. Moreover, they have shown potential for training to control impulsive eating. To test the hypothesis that training modulates early neural markers of response inhibition, the current study investigated how the N2 event‐related brain potential to high‐ and low‐calorie food images changes along Go‐/No‐Go training and how the N2 is related to later eating behavior. 50 healthy adults, (mBMI = 23.01) first completed a food Go/No‐Go task in which high‐ and low‐calorie food images were accompanied by Go‐and No‐Go‐cues with equal frequency. Participants then completed a training block in which high‐calorie foods were predominantly paired with a No‐Go cue and the low‐calorie foods with a Go cue, followed by a block with reversed coupling (order of the training blocks counterbalanced between participants). After each training, there was a snacking opportunity during which calorie intake was measured. Against our preregistered hypotheses, the N2‐amplitudes were not significantly affected by the calorie‐content and there was no training‐related modulation in the N2. In addition , food intake was not influenced by the preceding training blocks and the N2 amplitude did not predict the food intake. Our study suggests that the link between N2 obtained in a food‐related Go/No‐Go task and impulse control is not clear‐cut and may be limited to specific task characteristics. The results are of high importance as they question the previously assumed mechanism of Go/No‐Go training in food‐related inhibitory control.

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

ObjectiveTo test if the Finnish Defence Forces Basic Intellectual Ability Test scores at 20.1 years predicted risk of organic dementia or Alzheimer disease (AD).MethodsDementia was defined as inpatient or outpatient diagnosis of organic dementia or AD risk derived from Hospital Discharge or Causes of Death Registers in 2,785 men from the Helsinki Birth Cohort Study, divided based on age at first diagnosis into early onset (ResultsLower cognitive ability total and verbal ability (hazard ratio [HR] per 1 SD disadvantage >1.69, 95% confidence interval [CI] 1.01–2.63) scores predicted higher early-onset any dementia risk across the statistical models; arithmetic and visuospatial ability scores were similarly associated with early-onset any dementia risk, but these associations weakened after covariate adjustments (HR per 1 SD disadvantage >1.57, 95% CI 0.96–2.57). All associations were rendered nonsignificant when we adjusted for participant's education. Cognitive ability did not predict late-onset dementia risk.ConclusionThese findings reinforce previous suggestions that lower cognitive ability in early life is a risk factor for early-onset dementia.

International adoptees are at an increased risk of emotional and behavioral problems, especially those who are adopted at an older age. We took a new approach in our study of the network structure and predictability of emotional and behavioral problems in internationally adopted children in Finland. Our sample was from the on-going adoption study and comprised 778 internationally adopted children (387 boys and 391 girls, mean age 10.5 (SD 3.4) years). Networks were estimated using Gaussian graphical models and lasso regularization for all the children, and separately for those who were adopted at different ages. The results showed that anxiety/depressive symptoms, social problems, and aggressiveness were the most central symptom domains. Somatic symptoms were the least central and had the weakest effect on the other domains. Similarly, aggressiveness, social problems, and attention problems were high in terms of predictability (73-65%), whereas internalizing problems were relatively low (28-56%). There were clear but local age-group differences in network structure, symptom centrality, and predictability. According to our findings, network models provide important additional information about the centrality and predictability of specific symptom domains, and thus may facilitate targeted interventions among international adoptees.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Food Go/No-Go training aims to alter implicit food biases by creating associations between perceiving unhealthy foods and withholding a dominant response. Asking participants to repeatedly inhibit an impulse to approach unhealthy foods can decrease unhealthy food intake in laboratory settings. Less is known about how people engage with app-based Go/No-Go training in real-world settings and how this might relate to dietary outcomes. This pragmatic observational study investigated associations between the number of completed app-based food Go/No-Go training trials and changes in food intake (Food Frequency Questionnaire; FFQ) for different healthy and unhealthy food categories from baseline to one-month follow-up. In total, 1234 participants (m(BMI) = 29 kg/ m2, m(age) = 43years, 69% female) downloaded the FoodT app and completed food-Go/No-Go training at their own discretion (mean number of completed sessions = 10.7, sd = 10.3, range: 1-122). In pre-registered analyses, random-intercept linear models predicting intake of different foods, and controlled for baseline consumption, BMI, age, sex, smoking, metabolic syndrome, and dieting status, revealed small, significant associations between the number of completed training trials and reductions in unhealthy food intake (b = -0.0005, CI95 = [-0.0007;0.0003]) and increases in healthy food intake (b = 0.0003, CI95 = [0.0000; 0.0006]). These relationships varied by food category, and exploratory analyses suggest that more temporally spaced training was associated with greater changes in dietary intake. Taken together, these results imply a positive association between the amount of training completed and beneficial changes in food intake. However, the results of this pragmatic study should be interpreted cautiously, as self-selection biases, motivation and other engagement-related factors that could underlie these associations were not accounted for. Experimental research is needed to rule out these possible confounds and establish causal dose-response relationships between patterns of engagement with food Go/No-Go training and changes in dietary intake.

Individual circadian preference types and sleep EEG patterns related to spindle characteristics, have both been associated with similar cognitive and mental health phenotypes. However, no previous study has examined whether sleep spindles would differ by circadian preference. Here, we explore if spindle amplitude, density, duration or intensity differ by circadian preference and whether these associations are moderated by spindle location, frequency, and time distribution across the night. The participants (N = 170, 59% girls; mean age = 16.9, SD = 0.1 years) filled in the shortened 6-item Horne-Östberg Morningness-Eveningness Questionnaire. We performed an overnight sleep EEG at the homes of the participants. In linear mixed model analyses, we found statistically significant lower spindle amplitude and intensity in the morning as compared to intermediate (P 0.06 for spindle duration and density). Spindle frequency moderated the associations (P 0.2 for fast (>13 Hz)). Growth curve analyses revealed a distinct time distribution of spindles across the night by the circadian preference: both spindle amplitude and intensity decreased more towards morning in the morning preference group than in other groups. Our results indicate that circadian preference is not only affecting the sleep timing, but also associates with sleep microstructure regarding sleep spindle phenotypes.

Introduction: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. Methods: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. Results: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI = 0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b = -0.01; p = 0.010) for participants with higher versus lower positive psychosocial score in childhood. Conclusions: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted. (C) 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Summary Background The associations of social isolation and loneliness with premature mortality are well known, but the risk factors linking them remain unclear. We sought to identify risk factors that might explain the increased mortality in socially isolated and lonely individuals. Methods We used prospective follow-up data from the UK Biobank cohort study to assess self-reported isolation (a three-item scale) and loneliness (two questions). The main outcomes were all-cause and cause-specific mortality. We calculated the percentage of excess risk mediated by risk factors to assess the extent to which the associations of social isolation and loneliness with mortality were attributable to differences between isolated and lonely individuals and others in biological (body-mass index, systolic and diastolic blood pressure, and handgrip strength), behavioural (smoking, alcohol consumption, and physical activity), socioeconomic (education, neighbourhood deprivation, and household income), and psychological (depressive symptoms and cognitive capacity) risk factors. Findings 466 901 men and women (mean age at baseline 56·5 years [SD 8·1]) were included in the analyses, with a mean follow-up of 6·5 years (SD 0·8). The hazard ratio for all-cause mortality for social isolation compared with no social isolation was 1·73 (95% CI 1·65–1·82) after adjustment for age, sex, ethnic origin, and chronic disease (ie, minimally adjusted), and was 1·26 (95% CI 1·20–1·33) after further adjustment for socioeconomic factors, health-related behaviours, depressive symptoms, biological factors, cognitive performance, and self-rated health (ie, fully adjusted). The minimally adjusted hazard ratio for mortality risk related to loneliness was 1·38 (95% CI 1·30–1·47), which reduced to 0·99 (95% CI 0·93–1·06) after full adjustment for baseline risks. Interpretation Isolated and lonely people are at increased risk of death. Health policies addressing risk factors such as adverse socioeconomic conditions, unhealthy lifestyle, and lower mental wellbeing might reduce excess mortality among the isolated and the lonely. Funding Academy of Finland, NordForsk, and the UK Medical Research Council.

Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Methods. Participants (N = 2011) were from the on- going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m(2)) measurements in 2007 and 2011 and genetic information were linked to comprehensive register based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome- wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. Results. The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b) = -0.22; 95% Confidence Intervals [CI] = -0.29,-0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b = -0.84; 95% CI = -1.77, 0.09). Conclusion. The findings indicate that education could be a protective factor against obesity in advanced countries. (C) 2017 Elsevier Inc. All rights reserved.

Background Prechoolers’ significant portions of sedentary time (ST) is a public-health concern due to its high prevalence and negative health consequences. However, few studies have explored correlates of preschoolers’ ST covering individual-, home- and preschool- factors within one study. The aim of this study was to identify the associations between multiple individual-, home- and preschool-level factors and preschoolers’ ST. In addition, it was studied how much individual-, home- and preschool-level factors explained the variance in children’s ST. Methods A total of 864 children aged three to six, their parents and 66 preschools participated in the cross-sectional DAGIS study, which occurred between 2015 and 2016. The children wore an accelerometer for 1 week. Guardians, principals and early educators completed questionnaires covering the potential correlates of children’s ST, for example, temperament, practices, self-efficacy and regulations. Multilevel regression analyses were conducted in multiple steps; calculation of marginal and conditional R2 values occurred in the final phase. Results Of the 29 studied correlates, the following factors remained significant in the final models. Being a boy (p p p = 0.014) were associated with lower ST. Higher parental perceived barriers related to children’s outside PA (p = 0.032) was associated with higher ST. None of the preschool setting factors remained significant in the final model. Approximately 11% of the variance in children’s ST was attributed to factors related to the individual level whereas 5% was attributed to home-level factors; and 2% to preschool-level factors. Conclusions This study identified a set of correlates of preschool children’s ST. Interventions aimed at reducing children’s ST should develop strategies targeting established correlates of preschoolers’ ST covering individual-, home- and preschool-level factors. The preschool-level factors included in this study explained little the variance in children’s ST. However, the included measures may not have captured the essential preschool-level factors that specifically influence children’s ST. Therefore, more studies are needed regarding potential preschool-level factors.

BackgroundMaternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions.MethodsWe analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records.ResultsHigher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26–1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17–0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00–0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12–0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction).ConclusionsDepression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P −8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P

Purpose: Physical activity, sleep problems, and symptoms of depression contribute to overall well-being. The factors are reciprocally associated, but the nature of these associations remains unclear. The present study examined whether sleep problems mediated the association between physical activity and depressive symptoms. Methods: The eligible population (n = 3596) consisted of adults from the ongoing, population-based Cardiovascular Risk in Young Finns Study started in 1980. Participants’ leisure-time physical activity was assessed with physical activity index (2007) and sleep problems with Jenkins’ Sleep Questionnaire in 2007 and 2011. Depressive symptoms were measured using modified Beck Depression Inventory in 2007 and 2012, from which the items reflecting sleep problems were excluded. Mediation analyses, through which the associations between the variables were examined, were adjusted for sex and a set of health-related covariates assessed in 2007 and 2011. Results: Physical activity was associated with decreased levels of sleep problems and depressive symptoms (P < 0.05). The association between physical activity and depressive symptoms (b = −0.10, P < 0.01) was partly mediated by sleep problems (proportion mediated = 0.36, P < 0.01). The adjustment for depressive symptoms at baseline attenuated the mediation effect (proportion mediated = 0.30, P > 0.05). Conclusions: Physical activity’s favorable contribution to depressive symptoms was mediated partly by sleep, but the mediation effect disappeared after adjusting for the previous depressive symptoms in adulthood.

In Finland, as well as all over the globe, great weight is put on the possibilities of large data collections and ‘big data’ for generating economic growth, enhancing medical research, and boosting health and wellbeing in totally new ways. This massive data gathering and usage is justified by the moral principle of improving health. The imperative of health thus legitimizes data collection, new infrastructures and innovation policy. It is also supported by the rhetoric of health promotion. New arrangements in health research and innovations in the health sector are justified, as they produce health, while the moral principle of health also obligates individual persons to pursue healthy lifestyles and become healthy citizens. I examine how, in this context of Finnish data-driven medicine, arguments related to privacy and autonomy become silenced when contrasted with the moral principle of health.

This study describes the role of ungrammatical utterances and disfluent speech in the creation of comprehension problems between the participants in group therapy sessions of preadolescents with autism. The speech of the autistic preadolescents included frequent disfluencies and morpho-syntactic problems, such as wrong case endings, ambiguous pronominal references, grammatically incoherent syntactic structures and inaccurate tenses, which caused problems of comprehension. Three different interactional trajectories occurred when solving the potential problems of comprehension following the morpho-syntactically disfluent turns. First, the disfluent turn sometimes led to a clarification request by a co-participant, either a therapist or another participant with ASD. The preadolescents with ASD showed interactional skilfulness in requesting clarification when faced with comprehension problems. Second, in contrast, other occurrences included one or several self-repairs by the speaker with ASD. In these cases, the other group participants either did not react or they encouraged the speaker to continue using discourse particles. If the self-repairing disfluencies led to a persisting problem of comprehension, the therapists sometimes intervened and resolved the problem. However, direct interventions by the therapists were infrequent because the participants with ASD were mostly able to resolve the comprehension problems by themselves. Third, some disfluent and/or grammatically incorrect turns were not treated as problematic by the co-participants nor by the speaker himself. This study describes the role of ungrammatical utterances and disfluent speech in the creation of comprehension problems between the participants in group therapy sessions of preadolescents with autism. The speech of the autistic preadolescents included frequent disfluencies and morpho-syntactic problems, such as wrong case endings, ambiguous pronominal references, grammatically incoherent syntactic structures and inaccurate tenses, which caused problems of comprehension. Three different interactional trajectories occurred when solving the potential problems of comprehension following the morpho-syntactically disfluent turns. First, the disfluent turn sometimes led to a clarification request by a co-participant, either a therapist or another participant with ASD. The preadolescents with ASD showed interactional skilfulness in requesting clarification when faced with comprehension problems. Second, in contrast, other occurrences included one or several self-repairs by the speaker with ASD. In these cases, the other group participants either did not react or they encouraged the speaker to continue using discourse particles. If the self-repairing disfluencies led to a persisting problem of comprehension, the therapists sometimes intervened and resolved the problem. However, direct interventions by the therapists were infrequent because the participants with ASD were mostly able to resolve the comprehension problems by themselves. Third, some disfluent and/or grammatically incorrect turns were not treated as problematic by the co-participants nor by the speaker himself.

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni, Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites., We are grateful to all families and participants who took part in these studies. We also acknowledge and appreciate the unique efforts of the research teams and practitioners contributing to the collection of this wealth of data. C. M. M. is supported by funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 721567. J. F. F. has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and 733206 (LifeCycle). R. M. F. and R. N. B. are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). D. L. C. is funded by the American Diabetes Association Grant 1-17-PDF-077. D. O. M-K. was supported by Dutch Science Organization (ZonMW-VENI Grant 916.14.023). N. M. W. is supported by an Australian National Health and Medical Research Council Early Career Fellowship (APP1104818). T. S. A. was partially funded by the Gene-Diet Interactions in Obesity (GENDINOB) project on behalf of GOYA male cohort data management and analyses and acknowledges the same. S. D. was supported by National Institute of Health Research. T. M. F. is supported by the European Research Council grant: 323195 SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).H.H.is funded by The Children's Hospital of Philadelphia Endowed Chair in Genomic Research. A. T. H. is supported by the Wellcome Trust Senior Investigator Awards (WT098395), National Institute for Health Research (NIHR) Senior Investigator Award (NF-SI-0611-10219). J. Hebebrand received grants from German Research Society, German Ministry of Education and Research. M-F. H. is currently supported by an American Diabetes Association (ADA) Pathway Program Accelerator Early Investigator Award (1-15-ACE-26). S. J. is supported by Helse Vest no. 23929, Bergen Forskningsstiftelse and KG Jebsen Foundation and University of Bergen. J. K. has been supported by the Academy of Finland Research Professor program (grants 265240 & 263278). J. P. K. is funded by a University of Queensland Development Fellowship (UQFEL1718945). H. L. has served as a speaker for Eli-Lilly and Shire and has received research grants from Shire; all outside the submitted work. C. M. L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138-27). S. E. M. was funded by an NHMRC Senior Reseach Fellowship (APP1103623). K. Panoutsopoulou is funded by a career development fellowship (grant 20308) and by the Wellcome Trust (WT098051). C. P. at UCL Institute of Child Health, with support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. I. P. was funded in part by the Wellcome Trust (WT205915), and the European Union's Horizon 2020 research, the European Union FP7-IDEAS-ERC Advanced Grant (GEPIDIAB, ERC-AG -ERC-294785), and innovation programme (DYNAhealth, H2020-PHC-2014-633595). R. C. R. is supported by CRUK (grant number C18281/A19169). J. G. S. is supported by an NHMRC Practitioner Fellowship Grant (APP1105807). J. T.; r is funded by the European Regional Development Fund (ERDF), the European Social Fund (ESF), Convergence Programme for Cornwall and the Isles of Scilly and the Diabetes Research and Wellness Foundation Non-Clinical Fellowship. N. V-T. is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2015 FI_B 00636), Generalitat de Catalunya. T. G. M. V was supported by ZonMW (TOP 40-00812-98-11010. J. F. W. is supported by the MRC Human Genetics Unit quinquennial programme QTL in Health and Disease. H. Y. is funded by Diabetes UK RD Lawrence fellowship (grant: 17/0005594). M. H. Z was supported by BBMRI-NL (CP2013-50). E. Z. is supported by the Wellcome Trust (098051). B. F. is supported by Novo Nordisk Foundation (12955) and an Oak Foundation Fellowship. S. S. and M-R. J. have received funding from the European Union's Horizon 2020 research and innovation programme [under grant agreement No 633595] for the DynaHEALTH action. P. R. N. was supported by the European Research Council (ERC), University of Bergen, KG Jebsen and Helse Vest. G. D. S. works within the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/1). D. A. L was supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement (Grant number 669545; DevelopObese), US National Institute of Health (grant: R01 DK10324), the UK Medical Research Council (grant: MC_UU_00011/6), Wellcome Trust GWAS grant (WT088806), an NIHR Senior Investigator Award (NF-SI-0611-10196) and the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. L. Paternoster was supported by the UK Medical Research Council Unit grants MC_UU_12013_5. N. J. T. is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). V.W.V.J. received an additional grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw-VIDI 016.136.361), a European Research Council Consolidator Grant (ERC-2014-CoG-648916) and funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and 733206 (LifeCycle). D. M. E. is funded by the UK Medical Research Council Unit grant MC_UU_12013_4, Australian Research Council Future Fellowship (FT130101709) and a NHMRC Senior Research Fellowship (GNT1137714). S. F. A. G. is funded by the Daniel B. Burke Endowed Chair for Diabetes Research and R01 HD056465. D. I. B. is supported by Spinozapremie (NWO-56-464-14192) and the Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB. M. I. M. is a Wellcome Senior Investgator and NIHR Senior Investigator supported by the Wellcome (090532, 098381, 203141), NIHR (NF-SI-0617-10090) and the US National Institute of Health (grant: R01 DK10324), the UK Medical Research Council (grant: MCiabetes UK RD Lawrence fellowship (grant: 17/0005594). M. H. Z was supported by BBMRI-NLNIHR Biomedical Research Centre, Oxford. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Background: Seasonal variation in glucose metabolism might be driven by changes in daylight. Melatonin entrains circadian regulation and is directly associated with daylight. The relationship between melatonin receptor 1B gene variants with glycemic traits and type 2 diabetes is well established. We studied if daylight length was associated with glycemic traits and if it modified the relationship between melatonin receptor 1B gene rs10830963 variant and glycemic traits. Materials: A population-based sample of 3422 18–78-year-old individuals without diabetes underwent an oral glucose tolerance test twice, an average 6.8 years (SD = 0.9) apart and were genotyped for rs10830963. Daylight data was obtained from the Finnish Meteorological Institute. Results: Cross-sectionally, more daylight was associated with lower fasting glucose, but worse insulin sensitivity and secretion at follow-up. Longitudinally, individuals studied on lighter days at follow-up than at baseline showed higher glucose values during the oral glucose tolerance test and lower Corrected Insulin Response at follow-up. GG genotype carriers in the rs10830963 became more insulin resistant during follow-up if daylight length was shorter at follow-up than at baseline. Conclusions: Our study shows that individual glycemic profiles may vary according to daylight, MTNR1B genotype and their interaction. Future studies may consider taking daylight length into account.Key messagesIn Western Finland, the amount daylight follows an extensive annual variation ranging from 4 h 44 min to 20 h 17 min, making it ideal to study the associations between daylight and glycemic traits. Moreover, this allows researchers to explore if the relationship between the melatonin receptor 1B gene rs10830963 variant and glycemic traits is modified by the amount of daylight both cross-sectionally and longitudinally.This study shows that individuals, who participated in the study on lighter days at the follow-up than at the baseline, displayed to a greater extent worse glycemic profiles across the follow-up.Novel findings from the current study show that in the longitudinal analyses, each addition of the minor G allele of the melatonin receptor 1B gene rs10830963 was associated with worsening of fasting glucose values and insulin secretion across the 6.8-year follow-up.Importantly, this study shows that in those with the rs10830963 GG genotype, insulin sensitivity deteriorated the most significantly across the 6.8-year follow-up if the daylight length on the oral glucose tolerance testing date at the follow-up was shorter than at the baseline.Taken together, the current findings suggest that the amount of daylight may affect glycemic traits, especially fasting glucose and insulin secretion even though the effect size is small. The association can very according to the rs10830963 risk variant. Further research is needed to elucidate the mechanisms behind these associations. In Western Finland, the amount daylight follows an extensive annual variation ranging from 4 h 44 min to 20 h 17 min, making it ideal to study the associations between daylight and glycemic traits. Moreover, this allows researchers to explore if the relationship between the melatonin receptor 1B gene rs10830963 variant and glycemic traits is modified by the amount of daylight both cross-sectionally and longitudinally. This study shows that individuals, who participated in the study on lighter days at the follow-up than at the baseline, displayed to a greater extent worse glycemic profiles across the follow-up. Novel findings from the current study show that in the longitudinal analyses, each addition of the minor G allele of the melatonin receptor 1B gene rs10830963 was associated with worsening of fasting glucose values and insulin secretion across the 6.8-year follow-up. Importantly, this study shows that in those with the rs10830963 GG genotype, insulin sensitivity deteriorated the most significantly across the 6.8-year follow-up if the daylight length on the oral glucose tolerance testing date at the follow-up was shorter than at the baseline. Taken together, the current findings suggest that the amount of daylight may affect glycemic traits, especially fasting glucose and insulin secretion even though the effect size is small. The association can very according to the rs10830963 risk variant. Further research is needed to elucidate the mechanisms behind these associations.

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. Electronic supplementary material The online version of this article (10.1007/s00787-018-1243-8) contains supplementary material, which is available to authorized users.

Objective: Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. Methods: A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks thorn days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child's mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory-II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. Results: Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. Conclusion: Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics. (C) 2018 Elsevier B.V. All rights reserved.

Modern biomedical and genetic studies require large study cohorts; blood donors have been suggested to represent an appropriate group for recruiting healthy cohorts. The Blood Service Biobank (BSB) in Finland was recently established to recruit blood donors willing to give broad biobank consent. The aim of the present study is to understand how the blood bank context influences views on donating samples and health data. We organised 61 interviews and 10 group discussions with current and potential blood donors. Using qualitative content analysis, we identified three discussion frameworks that summarise the results. We found that frequent blood donors associated the voluntary act of donation with caring for patients. The blood donation experience was considered to accommodate biobank participation, but also allowed critical observations on the integration of research data collection into blood donation. Research participants identified an important difference between the blood bank and biobank contexts. In the biobank context, the focus shifts from donating blood to patients into donating personal and genetic data for research use. Blood donors' anxiety over data use was balanced with their experience of the trustworthiness of the Blood Service. These experiences indicated that the new biobanking activity could be trusted to a familiar organisation. To build donors' trust, biobanks should invest in their institutional reputation, donor experience and dialogue with donors. These findings can be applied to other institutions that are considering setting up biobanks with broad consent for personal data use.

Finding relevant information from large document collections such as the World Wide Web is a common task in our daily lives. Estimation of a user’s interest or search intention is necessary to recommend and retrieve relevant information from these collections. We introduce a brain-information interface used for recommending information by relevance inferred directly from brain signals. In experiments, participants were asked to read Wikipedia documents about a selection of topics while their EEG was recorded. Based on the prediction of word relevance, the individual’s search intent was modeled and successfully used for retrieving new relevant documents from the whole English Wikipedia corpus. The results show that the users’ interests toward digital content can be modeled from the brain signals evoked by reading. The introduced brain-relevance paradigm enables the recommendation of information without any explicit user interaction and may be applied across diverse information-intensive applications.

Background Molecular aging biomarkers, such as epigenetic age predictors, predict risk factors of premature aging, and morbidity/mortality more accurately than chronological age in middle-aged and elderly populations. Yet, it remains elusive if such biomarkers are associated with aging-related outcomes earlier in life when individuals begin to diverge in aging trajectories. We tested if the Horvath epigenetic age predictor is associated with pubertal, neuroendocrine, psychiatric, and cognitive aging-related outcomes in a sample of 239 adolescents, 11.0–13.2 years-old. Results Each year increase in epigenetic age acceleration (AA) was associated with 0.06 SD units higher weight-for-age, 0.08 SD units taller height-for-age, -0.09 SD units less missed from the expected adult height, 13 and 16% higher odds, respectively, for each stage increase in breast/genitals development on the Tanner Staging Questionnaire and pubertal stage on the Pubertal Development Scale, 4.2% higher salivary cortisol upon awakening, and 18 to 34% higher odds for internalizing and thought problems on the Child Behavior Checklist (p values

Purpose: Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINAI (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children. Methods: We studied 186, 8-year-old children with genome-wide genotyping. We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229) derived from the CORNET meta-analyses. Salivary cortisol was measured across one day and in response to the Trier Social Stress Test for Children (TSST-C). Results: Mixed models, adjusted for covariates, showed that the PRS x sampling time interactions associated with diurnal (P

Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems. Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child's age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA. Results: Maternal history of depression diagnosed before pregnancy (mean difference = -0.25 SD units, 95% CI = -0.46 to -0.03) and greater antenatal depressive symptoms (-0.08 SD unit per I-SD unit increase, 95% CI = -0.16 to -0.004) were associated with child's lower epigenetic GA. Child's lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys. Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems.

We examined the effects of the emotional facial expressions of a virtual character (VC) on human frontal electroencephalographic (EEG) asymmetry (putatively indexing approach/withdrawal motivation), facial electromyographic (EMG) activity (emotional expressions), and social decision making (cooperation/defection). In a within-subjects design, the participants played the Iterated Prisoner's Dilemma game with VCs with different dynamic facial expressions (predefined or dependent on the participant's electrodermal and facial EMG activity). In general, VC facial expressions elicited congruent facial muscle activity. However, both frontal EEG asymmetry and facial EMG activity elicited by an angry VC facial expression varied as a function of preceding interactional events (human collaboration/defection). Pre-decision inner emotional-motivational processes and emotional facial expressions were dissociated, suggesting that human goals influence pre-decision frontal asymmetry, whereas display rules may affect (pre-decision) emotional expressions in human-VC interaction. An angry VC facial expression, high pre-decision corrugator EMG activity, and relatively greater left frontal activation predicted the participant's decision to defect. Both post-decision frontal asymmetry and facial EMG activity were related to reciprocal cooperation. The results suggest that the justifiability of VC emotional expressions and the perceived fairness of VC actions influence human emotional responses.

Objectives To assess differences relating to circadian preference in objectively measured sleep patterns from childhood to adolescence over a 9-year period. We hypothesized there is developmental continuity in sleep timing and duration according to circadian preference. Study design Young participants (N = 111, 65% girls) from a community- based birth cohort underwent sleep actigraphy at mean ages 8.1 (SD = 0.3), 12.3 (SD = 0.5), and 16.9 (SD = 0.1) years. A short version of MorningnessEveningness Questionnaire was administered in late adolescence. At each follow-up, sleep midpoint, duration, wake after sleep onset, sleep efficiency, and weekend catch-up sleep were compared between those reporting morning, intermediate, and evening preferences in late adolescence. Results Mixed model analyses indicated that sleep timing was significantly earlier among morning types compared with evening types at all ages (P values

Coffee’s long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = −0.0007, 95% C.I. −0.009 to 0.008, P = 0.87; β = −0.001, 95% C.I. −0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Music therapists use guided affect regulation in the treatment of mood disorders. However, self-directed uses of music in affect regulation are not fully understood. Some uses of music may have negative effects on mental health, as can non music regulation strategies, such as rumination. Psychological testing and functional magnetic resonance imaging (fMRI) were used explore music listening strategies in relation to mental health. Participants (n = 123) were assessed for depression, anxiety and Neuroticism, and uses of Music in Mood Regulation (MMR). Neural responses to music were measured in the medial prefrontal cortex (mPFC) in a subset of participants (n = 56). Discharge, using music to express negative emotions, related to increased anxiety and Neuroticism in all participants and particularly in males. Males high in Discharge showed decreased activity of mPFC during music listening compared with those using less Discharge. Females high in Diversion, using music to distract from negative emotions, showed more mPFC activity than females using less Diversion. These results suggest that the use of Discharge strategy can be associated with maladaptive patterns of emotional regulation, and may even have long-term negative effects on mental health. This finding has real-world applications in psychotherapy and particularly in clinical music therapy.

Background The aim of this study was to examine longitudinally in the general population (a) whether depressive symptoms co-occur with paranoid ideation from late adolescence to middle age (b) whether depressive subsymptoms are differently linked with paranoid ideation (c) whether depressive symptoms are associated with state-level or trait-level paranoid ideation. Methods Altogether 2109 subjects of the Young Finns study completed the Paranoid Ideation Scale of the Symptom Checklist-90 Revised and a modified version of the Beck Depression Inventory in 1992, 1997, 2001, 2007, and 2012, and the Beck Depression Inventory-II in 2007, 2011, and 2012. Results Higher self-rated depressive symptoms were associated with the course of more severe paranoid ideation over age, especially in late adolescence and early adulthood. Regarding depressive subsymptoms, the associations of negative attitude and performance difficulties with paranoid ideation were evident over age, whereas the influence of somatic symptoms (such as changes in sleep and appetite) was not significant until after early adulthood. Additionally, depressive symptoms were more evidently associated with the development of trait- than state-level paranoid ideation. Limitations Our study mostly captured mild depressive and paranoid symptoms. The results cannot be directly generalized to clinical populations. Conclusions Depressive symptoms were associated with the course of paranoid ideation from late adolescence to middle age. Patients with paranoid ideation might merit from evaluation of potential depressive symptoms, especially in late adolescence and early adulthood. Among patients with co-occurring depressive symptoms and paranoid ideation, there may be a substantial need for neurocognitive rehabilitation and community-based treatments.

BackgroundBeing breastfed in infancy has been shown to benefit neurodevelopment. However, whether the benefits persist to old age remains unclear.MethodsWe examined the associations between breastfeeding and its duration on cognitive ability in young adulthood and old age, and on aging-related cognitive change over five decades. In total, 931 men from the Helsinki Birth Cohort Study born in 1934–1944 in Finland took the Finnish Defence Forces Basic Intellectual Ability Test (total and verbal, arithmetic and visuospatial subtest scores) twice, at ages 20.2 and 67.9 years, and had data on breastfeeding (yes v. no) and its duration (‘never breastfed’, ‘up to 3’, ‘3 to 6’ and ‘6 or more months’). Linear and mixed model regressions tested the associations.ResultsAt 20.2 years, breastfed men had higher cognitive ability total and visuospatial subtest scores [mean differences (MDs) ranged between 3.0–3.9, p values < 0.013], and its longer duration predicted higher cognitive ability total and arithmetic and visuospatial subtest scores (MDs ranged between 3.0 and 4.8, p values < 0.039). At 67.9 years, breastfed men had higher total cognitive ability and all subtest scores (MDs ranged between 2.6 and 3.4, p values < 0.044) and its longer duration predicted all cognitive ability scores (MDs ranged between 3.1 and 4.7, p values < 0.050). Verbal subtest scores decreased over five decades in men who were never breastfed or were breastfed for 3 months or less, and increased in those breastfed for longer than 3 months.ConclusionsNeurodevelopmental advantages of breastfeeding and its longer duration persist into old age, and longer duration of breastfeeding may benefit aging-related change, particularly in verbal reasoning ability.

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.

Background A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjögren’s syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0349-z) contains supplementary material, which is available to authorized users.

The psychosocial determinants of prediabetes are poorly understood. The aims of our study were (1) to analyse the association between perceived social support in young adulthood and fasting glucose levels and prediabetes in mid-adulthood in a cohort of healthy Finns, (2) to explore whether body mass index (BMI), inflammation or depression mediate this relationship, (3) and to examine the association between social support trajectory groups and fasting glucose. A prospective design was used with an analytic sample of 1250 participants aged 3-18 years at baseline (1980) and aged 12-39 years when social support was measured. Fasting glucose and prediabetes were assessed 32 years after baseline. Linear and logistic regression was used to examine the association between social support and the outcome measures. A bootstrapping technique was used to examine mediation effects. Social support was associated with future glucose levels in women after adjusting for childhood socioeconomic status (SES) and youth depression (beta = -0.136, p = 0.001) and also predicted prediabetes in women after adjusting for childhood SES (beta = 1.31, 95 % CI 1.02 to 1.69, p = 0.031). Both associations were attenuated after adjusting for BMI in mid-adulthood. BMI was found to mediate the relationship between social support and prediabetes in women (beta for indirect effect beta = 0.09, SE = 0.03, CI = 0.03 to 0.16). Low perceived social support in young adulthood is associated with high fasting glucose and prediabetes in mid-adulthood in women but not men. The association between social support and prediabetes in women can be partly explained by BMI.

Earlier studies have revealed cross-modal visuo-tactile interactions in endogenous spatial attention. The current research used event-related potentials (ERPs) and virtual reality (VR) to identify how the visual cues of the perceiver’s body affect visuo-tactile interaction in endogenous spatial attention and at what point in time the effect takes place. A bimodal oddball task with lateralized tactile and visual stimuli was presented in two VR conditions, one with and one without visible hands, and one VR-free control with hands in view. Participants were required to silently count one type of stimulus and ignore all other stimuli presented in irrelevant modality or location. The presence of hands was found to modulate early and late components of somatosensory and visual evoked potentials. For sensory-perceptual stages, the presence of virtual or real hands was found to amplify attention-related negativity on the somatosensory N140 and cross-modal interaction in somatosensory and visual P200. For postperceptual stages, an amplified N200 component was obtained in somatosensory and visual evoked potentials, indicating increased response inhibition in response to non-target stimuli. The effect of somatosensory, but not visual, N200 enhanced when the virtual hands were present. The findings suggest that bodily presence affects sustained cross-modal spatial attention between vision and touch and that this effect is specifically present in ERPs related to early- and late-sensory processing, as well as response inhibition, but do not affect later attention and memory-related P3 activity. Finally, the experiments provide commeasurable scenarios for the estimation of the signal and noise ratio to quantify effects related to the use of a head mounted display (HMD). However, despite valid a-priori reasons for fearing signal interference due to a HMD, we observed no significant drop in the robustness of our ERP measurements.

We examined the association of perfectionism with depressive symptoms and tested whether psychological detachment from work would both mediate and moderate the association. The participants were 76 primary school teachers (87% female) who responded to measures of perfectionism (Multidimensional Inventory on Perfectionism in Sports adapted for teachers), psychological detachment from work (The Recovery Experience Questionnaire), and depressive symptoms (Beck Depression Inventory-II). Perfectionism comprised both adaptive and maladaptive dimensions. Adaptive perfectionism referred to striving for perfection, whereas maladaptive perfectionism involved negative reactions to imperfection and perceived pressure to be perfect. According to our results, negative reactions to imperfection were associated with higher depressive symptoms, and lower level of psychological detachment from work played a minor mediating role in the association. There was, however, no association between negative reactions to imperfection and higher depressive symptoms when detachment from work was high. Our findings suggest that striving for perfection and perceived pressure to be perfect might not contribute to depressive symptoms in teaching. Instead, teachers experiencing negative reactions to imperfection and low psychological detachment from work could be at risk for developing depressive symptoms. Finding ways to psychologically detach from work may benefit teachers characterized by negative reactions to imperfection. (C) 2017 Elsevier Ltd. All rights reserved.

Maternal depressive symptoms during pregnancy have been associated with child behavioural symptoms of attention-deficit/hyperactivity disorder (ADHD) in early childhood. However, it remains unclear if depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain times, and if maternal depressive symptoms after pregnancy add to or mediate any prenatal effects. 1,779 mother-child dyads participated in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. Mothers filled in the Center of Epidemiological Studies Depression Scale biweekly from 12+0–13+6 to 38+0–39+6 weeks+days of gestation or delivery, and the Beck Depression Inventory-II and the Conners’ Hyperactivity Index at the child’s age of 3 to 6 years (mean 3.8 years, standard deviation [SD] 0.5). Maternal depressive symptoms were highly stable throughout pregnancy, and children of mothers with consistently high depressive symptoms showed higher average levels (mean difference = 0.46 SD units, 95% Confidence Interval [CI] 0.36, 0.56, p < 0.001 compared to the low group), and proportion (32.1% vs. 14.7%) and odds (odds ratio = 2.80, 95% CI 2.20, 3.57, p < 0.001) of clinically significant ADHD symptoms. These associations were not explained by the effects of maternal depressive symptoms after pregnancy, which both added to and partially mediated the prenatal effects. Maternal depressive symptoms throughout pregnancy are associated with increased ADHD symptomatology in young children. Maternal depressive symptoms after pregnancy add to, but only partially mediate, the prenatal effects. Preventive interventions suited for the pregnancy period may benefit both maternal and offspring mental health.

Background: The association between depressive symptoms and subclinical atherosclerosis has been inconsistent. Purpose: We sought to replicate our previous study, which demonstrated a positive relation between depressive symptoms and subclinical atherosclerosis assessed with carotid intima-media thickness (IMT) in men, using a newer measurement of carotid IMT and a cumulative loading of depressive symptoms over three follow-ups. Methods: The sample comprised 996 adults (352 men) aged 30 to 45 years in 2007 from a prospective population-based Finnish sample. The participants completed a modified version of Beck Depression Inventory in 1992, 1997, and 2001. Carotid IMT was assessed with ultrasound in 2001 and 2007. Cardiovascular risk factors (i.e., body mass index, systolic blood pressure, low-density lipoprotein cholesterol, and smoking) were measured in childhood (1980) and in adulthood (2007). Results: We found no association between the accumulative depression index and carotid IMT before or after controlling for the traditional risk factors (all p values ≥0.67). Depressive symptoms did not predict IMT progression over two time points and the highest level of carotid wall thickening. Imputed and non-imputed data sets provided similar results. Results remained the same when men and women were analyzed separately. Additional analyses revealed no significant interactions between depressive symptoms and cardiovascular risk factors (i.e., body mass index and systolic blood pressure) on carotid IMT (all p values >0.15). Conclusions: The findings of this population-based study did not indicate any direct association between depressive symptoms and carotid IMT in asymptomatic, young adults.

Background Both hostile parenting and parental psychopathology have been shown to predict depression in the offspring. However, whether and how they interact in predicting the longitudinal course of depression from adolescence to adulthood remains unclear. Methods Participants were from the prospective Cardiovascular Risk in Young Finns study, aged 3–18 years at baseline in 1980. We used multilevel modeling for repeated measurements to examine the associations of hostile parenting (i.e., parental intolerance and emotional distance) and parental history of psychopathology with trajectories of depressive symptoms across five study phases from 1992 to 2012. Results On average, depressive symptoms decreased in a curvilinear pattern with age. A relatively steep decreasing trend was also observed among offspring of parents with a history of psychopathology but low intolerance. By contrast, among the offspring of parents with a history of psychopathology and high intolerance there was a rising trend in depressive symptoms starting from young adulthood. There was no similar interaction between parental history of psychopathology, emotional distance, and age. Limitations Non-standardized, parental self-report scales were used to measure hostile parenting. The observed effects were small, and the depressive symptoms scale applied in the study may not be used for measuring clinical depression. Conclusions Parental psychopathology might render individuals sensitive to the unfavorable characteristics of the caregiving environment. Intolerance towards the child can exacerbate the effects of parental psychopathology and have a long-term significance on the developmental trajectory of depressive symptoms over the life-course.

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children's responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4-15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child's rs4680 genotype, with stronger effects obtained for the val/val (G: G) genotype relative to val/met (A:G) (all p

Background Preterm birth (

OBJECTIVES Socioeconomic position (SEP) in childhood predicts cardiovascular health in adulthood but the underlying mechanisms remain unclear. Using a longitudinal study design, we examined the extent to which adult SEP acts as a pathway (mediator) connecting childhood SEP with adult cardiovascular health, and if upward social mobility mitigates the health-effects of early low SEP. METHOD The sample comprised 697 participants from a prospective Finnish cohort followed during 32 years. Childhood SEP was assessed from the parents in 1980 (participant mean age 10.9) and adulthood SEP was examined in 2007 and 2012 (participant mean age 43.2 in 2012). Both childhood and adulthood SEP scores comprised education, income, occupational status, and occupational stability. Ideal cardiovascular health was assessed in 2007 and 2012 according to the American Heart Association's guidelines. RESULTS Higher childhood SEP was associated with higher ideal cardiovascular health index in adulthood (β = 0.13, p < .001) independently of sex, age, childhood cardiovascular risk factors, and chronic conditions. Mediation analysis showed that adult SEP accounted for 33% of the association between childhood SEP and ideal cardiovascular health index. Upwardly mobile participants scored higher on ideal cardiovascular health in adulthood compared with participants staying in lower SEP (M = 4.05 vs. 3.56, p < .001). CONCLUSIONS Transmission of SEP over generations is a predictor of health inequalities, which should be considered in cardiovascular prevention. Although upward social mobility mitigates some of the effect of early SEP disadvantage on later cardiovascular health, childhood SEP remains an important predictor of future health. (PsycINFO Database Record

The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI). In an open-label design, 15 subjects received 15 mg of mirtazapine two hours prior to fMRI while 15 subjects served as a control group. We assessed the effects of mirtazapine on regional neural responses and dynamic functional connectivity associated with valence and arousal. Mirtazapine attenuated responses to unpleasant events in the right fronto-insular cortex, while modulating responses to arousing events in the core limbic regions and the cortical midline structures (CMS). Mirtazapine decreased responses to unpleasant and arousing events in sensorimotor areas and the anterior CMS implicated in self-referential processing and formation of subjective feelings. Mirtazapine increased functional connectivity associated with positive valence in the CMS and limbic regions. Mirtazapine triggers large-scale changes in regional responses and functional connectivity during naturalistic, emotional stimuli. These span limbic, sensorimotor, and midline brain structures, and may be relevant to the clinical effectiveness of mirtazapine.

Background Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1068-z) contains supplementary material, which is available to authorized users.