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Persistent psychological distress is more harmful than transient psychological distress, but little is known about the development of persistent distress. We examined whether some specific symptoms of the 12-item General Health Questionnaire (GHQ-12) were more important than others in predicting the persistence of psychological distress over a 3-year follow-up period among individuals who had at least moderate psychological distress at baseline (GHQ >= 3). Participants were from the UK Household Longitudinal Study (UKHLS; n = 6430) and British Household Panel Survey (BHPS; n = 5954). Sense of worthlessness, loss of self-confidence, loss of sleep over worry, and feelings of strain were associated with increasingly persistent distress. General happiness, feelings of unhappiness or depressed mood, and enjoyment of activities showed no such increasing associations. Symptoms of social functioning (capability of making decisions, concentration problems, feelings of usefulness, ability to face problems) showed some but not consistent associations. These results suggest that feelings of worthlessness, loss of self-confidence, loss of sleep over worry, and strain may be particularly important markers for persistent psychological distress.

Special issue: Amor Narratio: A Festschrift For Catherine Kohler Riessman There are many aspects of Catherine Kohler Riessman’s narrative scholarship which have established her international reputation in the field. This contribution pays tribute to the role she has played as a mentor, both through her written work and in her practice. Mentoring, which is time-consuming and painstaking work, is a critical but widely unacknowledged aspect of scholarship, which is often portrayed as an individual endeavor, the accomplishment of the name or names which appear on the publications. The article argues that all scholars are part of a larger cycle, situated mid-stream, between those who have come before and those who will follow. There are many questions surrounding the meaning of mentorship: who should do it and who receive it; if and how it should be institutionalized, calibrated, and recognized; and more. Taking Riessman’s example as its focus, the article critically examines the importance of mentoring and its role in forming, sustaining, and nourishing community

OBJECTIVES To better understand and compare effects of aging and education across domains of language and cognition, we investigated whether 1) these domains show different associations with age and education, 2) these domains show similar patterns of age-related change over time, and 3) education moderates the rate of decline in these domains. METHODS We analyzed data from 306 older adults aged 55-85 at baseline of whom 116 returned for follow-up 4-8 years later. An exploratory factor analysis identified domains of language and cognition across a range of tasks. A confirmatory factor analysis analyzed cross-sectional associations of age and education with these domains. Subsequently, mixed linear models analyzed longitudinal change as a function of age and moderation by education. RESULTS Two language domains, i.e., semantic control and semantic memory efficiency, and two cognitive domains, i.e., working memory and cognitive speed, were identified. Older age negatively affected all domains, but semantic memory efficiency and higher education positively affected all domains except cognitive speed at baseline. In language domains, a steeper age-related decline was observed after age 73-74 compared to younger ages, while cognition declined linearly with age. Greater educational attainment did not protect the rate of decline over time in any domain. DISCUSSION Separate domains show varying effects of age and education at baseline, language versus cognitive domains show dissimilar patterns of age-related change over time, and education does not moderate the rate of decline in these domains. These findings broaden our understanding of age effects on cognitive and language abilities by placing observed age differences in context. Objectives: To better understand and compare effects of aging and education across domains of language and cognition, we investigated whether (a) these domains show different associations with age and education, (b) these do- mains show similar patterns of age-related change over time, and (c) education moderates the rate of decline in these domains. Method: We analyzed data from 306 older adults aged 55–85 at baseline of whom 116 returned for follow-up 4–8 years later. An exploratory factor analysis identified domains of language and cognition across a range of tasks. A confirmatory factor analysis analyzed cross-sectional associations of age and education with these domains. Subsequently, mixed linear models analyzed longitudinal change as a function of age and moderation by education. Results: We identified 2 language domains, that is, semantic control and semantic memory efficiency, and 2 cognitive domains, that is, working memory and cognitive speed. Older age negatively affected all domains except semantic memory efficiency, and higher education positively affected all domains except cognitive speed at baseline. In language domains, a steeper age-related decline was observed after age 73–74 compared to younger ages, while cognition declined linearly with age. Greater educational attainment did not protect the rate of decline over time in any domain. Discussion: Separate domains show varying effects of age and education at baseline, language versus cognitive domains show dissimilar patterns of age-related change over time, and education does not moderate the rate of decline in these domains. These findings broaden our understanding of age effects on cognitive and language abilities by placing observed age differences in context.

This paper offers a comprehensive analysis of the morphosyntactic, semantic and pragmatic features of Nivkh demonstratives, which represent a typologically interesting example of an exceptionally elaborated speaker-anchored deictic system. The deictic properties of the demonstratives can be described either in terms of a binary system with the opposition between ‘proximal’ and ‘non-proximal’ areas as viewed from the deictic centre, or in terms of a multiple system that is organised hierarchically and may be divided into primary and secondary systems, which together define fifteen spatial zones around the deictic centre. Beyond spatial proximity, the demonstratives may also encode a number of non-deictic features such as quality, quantity, dimension, preciseness of location, and visibility. This paper distinguishes between six morphosyntactic classes of demonstratives and shows how the different deictic and non-deictic features correlate with their pragmatic uses.

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.

Biobank operations started officially in Finland in 2013 when the Biobank Act defining and regulating biobank operations came into force. Since then, ten biobanks have been established and they have started to collect new prospective samples with broad consent. The main corpus of biobank samples, however, consists of approximately 10 million “legacy samples”. These are old diagnostic or research samples that were transferred to biobanks in accordance with the Biobank Act. The focus of this article is on ambiguities concerning these legacy samples and their transfer in terms of legality, human rights, autonomy, and social sustainability. We analyse the Finnish biobank operations in the context of international regulation, such as the European Convention of Human Rights, the Oviedo Convention, European Charter of Fundamental Rights, the GDPR, and EU Clinical Trials Regulation, and show that the practice of using legacy samples is at times problematic in relation to this regulatory framework. We argue that the prevailing interpretations of these regulations as translated into the Finnish biobank practices undermine the autonomy of individuals by not giving individuals a right to consent or an actionable right to opt-out of the transfer of these legacy samples to the biobank. This is due to the fact that individuals are not given effective notification of such transfers. Thus, issues regarding the legal status of the biobank samples and the social sustainability of biobank operations remain a challenge for biobanks in Finland despite governmental efforts to create pioneering, comprehensive, and enabling legislation. Biobank operations started officially in Finland in 2013 when the Biobank Act defining and regulating biobank operations came into force. Since then, ten biobanks have been established and they have started to collect new prospective samples with broad consent. The main corpus of biobank samples, however, consists of approximately 10 million “legacy samples”. These are old diagnostic or research samples that were transferred to biobanks in accordance with the Biobank Act. The focus of this article is on ambiguities concerning these legacy samples and their transfer in terms of legality, human rights, autonomy, and social sustainability. We analyse the Finnish biobank operations in the context of international regulation, such as the European Convention of Human Rights, the Oviedo Convention, European Charter of Fundamental Rights, the GDPR, and EU Clinical Trials Regulation, and show that the practice of using legacy samples is at times problematic in relation to this regulatory framework. We argue that the prevailing interpretations of these regulations as translated into the Finnish biobank practices undermine the autonomy of individuals by not giving individuals a right to consent or an actionable right to opt-out of the transfer of these legacy samples to the biobank. This is due to the fact that individuals are not given effective notification of such transfers. Thus, issues regarding the legal status of the biobank samples and the social sustainability of biobank operations remain a challenge for biobanks in Finland despite governmental efforts to create pioneering, comprehensive, and enabling legislation.

Special Section: Self-Tracking, Embodied Differences, and the Politics and Ethics of Health This article concerns the relation between health, the embodied self-tracking subject and the environment in postsocialist China. Instead of simply expanding the framework of neoliberal subject to the question of health and the phenomenon of tracking and sharing data of “smog jog” in the Chinese context, this article addresses the following two inter-related questions: (1) how might an investigation of the practices of self-tracking “smog jog” in the context of postsocialist China afford a reconsideration of health; (2) how might an examination of the ways in which health is interpreted, performed and negotiated through practices of monitoring, measuring and recording a jog and the air quality in postsocialist China rework the conception of self-tracking. This article examines posts on Sina Weibo, which is one of the most popular social media platforms in China, in which Weibo users record and describe their jog in the smog. It argues that the configuration and performance of health and the embodied self-tracking subjects are multiple, and are informed by, negotiated with and find expressions in the environment in postsocialist China.

How general are our findings concerning the evolution and development of life forms? I will discuss this question of generality and the related question concerning the existence of lawlike generalizations with specific reference to evolutionary developmental biology (evo-devo). On the one hand, evo-devo suggests that the evolution and development of life forms is more contingent than we have previously presumed, thus showing that we have accidental and non-generalizable results concerning evolutionary and developmental phenomena. On the other hand, evo-devo reveals the existence of generality-maintaining mechanisms, thus showing that certain evolutionary and developmental generalizations have stability and necessity. These two findings suggest a picture of evolution as being both stable and contingent, repeatable and unique, and generalizable and non-generalizable. This picture of evolution was already present during the Modern Synthesis. At the same time, evo-devo has provided us with new insights into what are generality-destroying, generality-maintaining, and generality-creating mechanisms behind the evolution and development of life forms.

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).

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

Since our moral and legal judgments are focused on our decisions and actions, one would expect information about the neural underpinnings of human decision-making and action-production to have a significant bearing on those judgments. However, despite the wealth of empirical data, and the public attention it has attracted in the past few decades, the results of neuroscientific research have had relatively little influence on legal practice. It is here argued that this is due, at least partly, to the discussion on the relationship of the neurosciences and law mixing up a number of separate issues that have different relevance on our moral and legal judgments. The approach here is hierarchical; more and less feasible ways in which neuroscientific data could inform such judgments are separated from each other. The neurosciences and other physical views on human behavior and decision-making do have the potential to have an impact on our legal reasoning. However, this happens in various different ways, and too often appeal to any neural data is assumed to be automatically relevant to shaping our moral and legal judgments. Our physicalist intuitions easily favor neural-level explanations to mental-level ones. But even if you were to subscribe to some reductionist variant of physicalism, it would not follow that all neural data should be automatically relevant to our moral and legal reasoning. However, the neurosciences can give us indirect evidence for reductive physicalism, which can then lead us to challenge the very idea of free will. Such a development can, ultimately, also have repercussions on law and legal practice.

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.

The aim of the present study was to investigate whether the recognition speed of Finnish nominal base forms varies as a function of their paradigmatic complexity (stem allomorphy) or productivity status. Nikolaev et al. (2014) showed that words with greater stem allomorphy from an unproductive inflectional class are recognized faster than words with lower stem allomorphy from a productive inflectional class. Productivity of an inflectional paradigm correlates with the number of stem allomorphs in languages like Finnish in that unproductive inflectional classes tend to have higher stem allomorphy. We wanted to distinguish which of these two characteristics provides the benefit to speed of recognition found by Nikolaev et al. (2014). The current study involved a lexical decision task comparing three categories of words: unproductive with three or more stem allomorphs, unproductive with two stem allomorphs, and productive with two stem allomorphs. We observed a facilitation effect for word recognition only for unproductive words with three or more stem allomorphs, but not for unproductive words with two allomorphs. This effect was observed particularly in words of low to moderate familiarity. The findings suggest that high stem allomorphy, rather than productivity of the inflectional class, is driving the facilitation effect in word recognition.

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.

The oxytocin receptor gene (OXTR) may function as a "plasticity gene" that increases or decreases sociability in those individuals susceptible to growing up in a beneficial versus more adverse environment. This study used data from 2289 (55% female) participants from the ongoing prospective Young Finns Study. Maternal emotional warmth was assessed in 1980 when the participants were 3-18 years old. Participants' sociability temperament was measured at five follow-ups, from 1992 to 2012. Emotional warmth in childhood and OXTR genotype were not directly associated with temperamental sociability. We found a nominally significant gene environment interaction (p = .03) suggesting that participants with a genetic profile of rs1042778 T-allele and rs2254298 A-allele are affected high versus low emotional warmth, whereas homozygotes of both G-alleles are unaffected by the same environmental influence. Our findings should be, however, interpreted as a null result as the interaction effect did not survive correction for multiple testing.

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 FK506-binding protein 51 is involved in hypothalamic-pituitary-adrenal axis regulation. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene have been shown to interact with retrospectively self-reported early life stress (ELS) in patients with psychiatric disorders. We examined interactions between three selected FKBP5 SNPs and self-reported and objectively recorded ELS in relation to depressive symptoms in midlife. Methods This study comprised 1431 Helsinki Birth Cohort Study participants genotyped for FKBP5 SNPs shown to alter cortisol metabolism (rs1360780, rs9470080, and rs9394309). Participants completed the Beck Depression Inventory (BDI) at ages 61.5 years (time 1) and 63.4 years (time 2); 165 and 181 participants were separated from their parents in childhood as a result of evacuations during World War II as indicated by self-reports and the Finnish National Archives registry, respectively. Results Associations between self-reported and objectively recorded ELS, but not stressful events in midlife, and the mean BDI score (average of time 1 and time 2) or mild to severe BDI scores (10–63 points at time 1 and time 2), or both, were moderated by the FKBP5 variants ( p values for interactions p values between self-reported and objectively recorded ELS in these interactions > .18). Mean BDI scores or odds for having mild to severe BDI scores, or both, increased according to number of minor alleles and haplotypes derived from these alleles in the separated groups, but not in the nonseparated groups. Conclusions FKBP5 variations in combination with self-reported and objectively recorded ELS predict more pronounced depressive symptoms in midlife. Our findings confirm previous retrospective findings in a prospective epidemiologic study setting.

Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.

This article presents results from a Finnish focus group's study conducted among participants of a project called GeneRISK, in which the participants received a personal risk score for having a cardiovascular event based on genetic analysis, lifestyle and laboratory results. In the discussions, interpretations of the genetic risk score and its meaning were incorporated into personal narratives of health and illness. We argue that instead of serving as an explanation for health and illness, which can help guide people's lives and choices, the genetic risk information became an object of explanation. Therefore, the risk information did not create new conceptions of personal risk, nor did it generate enough power to push people to change their lifestyles. Instead, the risk information was used to strengthen the existing impression of personal risk and the narrative of personal health and illness.

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.

During the past decade, in Finland and elsewhere, biomedicine and genomics-related initiatives have been organized under the sociotechnical imaginary of personalized medicine. Within this imaginary, the medical future is promoted and made up, and the activities often subtly change the very meaning of what the imaginary of personalized medicine entails. In this paper, we study the Finnish strategies and pursuits addressing the utilization of genomics to advance personalized medicine. We build our analysis on previous research on sociotechnical imaginaries (Jasanoff & Kim, 2015) and the hype and expectations surrounding emerging technologies (Borup et al., 2006; Brown & Michael, 2003; Brown, 2003). We emphasize that the sociotechnical imaginary requires practical maintenance. In our analysis we address both rhetorical and action framings related to the making of personalized medicine and point out that activities of maintenance simultaneously pursue and reconfigure the imaginary of personalized medicine. Furthermore, our analysis shows that the focus of advocacy in personalized medicine has shifted from the promise of health to the promise of wealth as innovation policy and data-driven medicine have become the key framings.

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.

Reading a word activates morphologically related words in the mental lexicon. People with Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI) often have difficulty retrieving words, though the source of this problem is not well understood. To better understand the word recognition process in aging and in neurodegenerative disorders such as MCI and AD, we investigated the nature of the activation of morphologically related family members in 22 Finnish speakers with AD, 24 with MCI, and 17 cognitively healthy elderly. We presented Finnish monomorphemic (base form) nouns in a single-word lexical decision experiment to measure the speed of word recognition and its relation to morphological and lexical variables. Morphological variables included morphological family size (separate for compounds and derived words) and pseudo-morphological family size (including the set of words that have a partially overlapping form but that do not share an actual morpheme, e.g., pet and carpet, or corn and corner). Pseudo-morphological family size was included to examine the influence of words with orthographic (or phonological) overlap that are not semantically related to the target words. Our analyses revealed that younger and elderly controls and individuals with MCI or AD were influenced by true morphological overlap (overlapping forms that also share meaning), as well as by the word's pseudo morphological family. However, elderly controls and individuals with MCI or AD seemed to rely more on form overlap than young adults. This demonstrates that an increased reliance on form-based aspects of language processing in Alzheimer's disease is not necessarily due to a partial loss of access to semantics, but might be explained in part by a common age-related change of processes in written word recognition. (C) 2018 The Author(s). Published by Elsevier Ltd.

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.

Publisher's version (útgefin grein), Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk., We want to thank Susanne Sauer and Maik Ködel for their technical assistance and Jessica Keverne for language editing. We thank all mothers who took part in the on-going PREDO study. We are grateful to all the families in Norway who participate in the on-going MoBa cohort study. We thank the Drakenstein Child Health Study staff, and the clinical and administrative staff of the Western Cape Government Department of Health at Paarl Hospital and at the clinics for support of the Study. We also thank our collaborators and students. Finally, we thank all mothers and children enroled in the Drakenstein Child Health Study. We thank the research participants and employees of 23andMe, Inc. for their contribution to this study. This work was supported by the Academy of Finland (E.K., H.L., K.R., and J.L.); University of Helsinki Research Funds (J.L., M.L.P., and H.L.), British Heart Foundation (RMR); Tommy’s (RMR); European Commission (EK, KR, Horizon 2020 Award SC1–2016-RTD-733280 RECAP); NorFace DIAL (E.K., KR PremLife); Foundation for Pediatric Research (E.K.); Juho Vainio Foundation (E.K.); Novo Nordisk Foundation (E.K.); Signe and Ane Gyllenberg Foundation (E.K., K.R.); Sigrid Jusélius Foundation (E.K.); Finnish Medical Foundation (H.L.); Jane and Aatos Erkko Foundation (H.L.); Päivikki and Sakari Sohlberg Foundation (H.L., P.M.V.); the Clinical Graduate school in Pediatrics and Obstetrics/Gynaecology in University of Helsinki (P.M.V.). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (grant no 221097). This work was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The Drakenstein Child Health Study is supported by the Bill and Melinda Gates Foundation (OPP 1017641); with additional support for this work from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NICHD) under Award Number R21HD085849; and the Fogarty International Center (FIC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support for H.J.Z., D.J.S. and N.K., and for research reported in this publication was by the South African Medical Research Council (SAMRC); N.K. receives support from the SAMRC under a Self-Initiated Research Grant. The views and opinions expressed are those of the authors and do not necessarily represent the official views of the SAMRC. This work was also funded by the German Federal Ministry of Education and Research through the Research Consortium Integrated Network IntegraMent (grant 01ZX1314H) under the auspices of the e:Med Programme (NSM). The UCI cohort was supported by a European Research Area Network (ERA Net) Neuron grant (01EW1407A, CB) and National Institutes of Health grant (R01 HD-060628, CB) as well as NIH grant R01 MH-105538 (PDW). This work was also funded by the Canadian Institute for Advanced Research, Child and Brain Development Program, Toronto, ON, Canada (KJOD).

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.

Many studies suggest that in poker, “amount of money wagered” and “time spent playing” are prominent predictors of problem gambling. These observations are in discord with anecdotal and empirical evidence. Due to the inherent skill component in poker, active players who play for long hours attempting to make a profit – sometimes by wagering large amounts of money – might be labeled as problem gamblers despite having high levels of well-being and financial agency. In three on-line correlative studies, we assessed the associations between poker experience, problem gambling (the South Oaks Gambling Screen [SOGS] and the Problem Gambling Severity Index [PGSI] scores) and various measures of social and emotional well-being, self-control and emotion regulation. Problem gambling severity predicted reduced well-being, self-control, and increased social anomie and detrimental emotion regulation. Experienced poker players reported high problem gambling severity, but none of the adverse consequences therein. Therefore, a discrepancy was exposed concerning the validity of SOGS and PGSI. We conclude that these measures may not be valid in assessing “problematic”/detrimental gambling in poker playing populations, especially in the case of experienced players, who play for long hours in order to make money– the concepts of problem gambling and poker experience seem to be disentangled.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. © 2015, The Author(s). Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

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.

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.

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