Search

Increased self-focus is a core factor in the psychopathology of depression. Cortical midline structures (CMS) are implicated in the neurobiology of self, depression and antidepressant treatment response. Mirtazapine, an antidepressant that increases serotonin and norepinephrine release, enhances processing of positive and attenuates processing of negative emotional information in healthy volunteers after a single dose. These early changes, which are opposite to the negative information bias in depression, may be important for the therapeutic effect of mirtazapine. It nevertheless remains unresolved whether/how mirtazapine specifically influences processing of self-referential emotional information. Half of the healthy volunteers ( n=15/30) received a single dose of mirtazapine, in an open-label design, two hours before functional magnetic resonance imaging (fMRI), and the other half was scanned as a control group without medication. During fMRI the participants categorized positive and negative self-referential adjectives. Mirtazapine attenuated responses to self-referential processing in the medial prefrontal cortex and the anterior cingulate cortex. Mirtazapine further decreased responses to positive self-referential processing in the posterior cingulate cortex and parietal cortex. These decreased responses of the CMS suggest that mirtazapine may rapidly improve the ability of the CMS to down-regulate self-referential processing. In depressed patients, this could lead to decreased self-focus and rumination, contributing to the antidepressant effect.

We examined whether prevalence of social class discrimination-and its association with psychological distress-has changed between 1990s and 2010s in the United States. Data were from the original Midlife in the United States (MIDUS) study with data collections in 1995-1996 (n = 2931) and 2004-2005 (n = 1708), and the new MIDUS Refresher sample from 2011 to 2014 (n = 2543). Socioeconomic status (SES) became more strongly associated with self-rated discrimination over time, with individuals with the lowest SES experiencing more discrimination (B = 0.75, p < .001) and those with the highest SES less discrimination (B = 0.36, p < .001) over time: at baseline, the difference in self-rated discrimination between the highest and lowest SES groups was 15.3% versus 10.8% (4.7% point difference). This difference increased to 20.0% versus 7.4% in the last study wave (12.6% point difference). Association between self-reported discrimination and psychological distress strengthened over time, but the associations between socioeconomic indicators and distress did not change. The results suggest that people with low SES had higher risk of encountering unfair and disrespectful treatment in the 2010s compared to the 1990s.

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Background Examining the correlates of adolescent’s physical activity (PA) and how they may differ according to the intersection of gender and family socioeconomic status (SES) can support the development of tailored interventions to more effectively promote adolescents’ PA. This study explored how the associations between psychosocial, behavioural and environmental factors and adolescent’s PA differed according to gender and family SES. Methods This study used data from the Dutch Youth Health Survey 2015. Adolescents (n = 9068) aged 12–19 were included in the study. The associations between psychosocial, behavioural, and environmental factors and PA (days per week engaging in at least one hour of PA) were examined with multilevel linear regression analysis. Potential interactions between these correlates, gender and family SES were explored. Results On average, adolescents engaged in at least one hour of PA for 4,2 days per week. Poor self-perceived health, low peer social support, and a weak connection with the environment were all associated with lower PA in adolescents. Daily smoking, cannabis use, risk of problematic gaming and social media use, as well as lack of daily consumption of fruit, vegetables, water and breakfast were associated with lower PA, whereas binge drinking was not. Interactions revealed that poor self-perceived health was associated with lower PA in adolescents from moderate- and high-SES families, but not in low-SES adolescents, whereas cannabis use was only associated with lower PA amongst low-SES adolescents. Low peer social support was associated with lower PA across all groups, but it was most strongly associated with lower PA amongst male adolescents from low-SES families than in other subgroups. Amongst low-SES males, low peer social support was associated with a 1.47 reduction in days engaging in sufficient PA, compared with a 0.69 reduction for high-SES males. Conclusions This study identified several psychosocial, behavioural and environmental factors that can be targeted to potentially increase adolescent’s PA. We also found that correlates of PA differed according to the intersection of gender and family SES. Our findings suggest that PA interventions should be tailored according to gender and SES to address the specific needs, barriers and facilitators of different subgroups.

Aging is accompanied by difficulties in auditory information processing, especially in more complex sound environments. Choir singing requires efficient processing of multiple sound features and could, therefore, mitigate the detrimental effects of aging on complex auditory encoding. We recorded auditory event-related potentials during passive listening of sounds in healthy older adult (>= 60 years) choir singers and nonsinger controls. We conducted a complex oddball condition involving encoding of abstract regularities in combinations of pitch and location features, as well as in two simple oddball conditions, in which only either the pitch or spatial location of the sounds was varied. We analyzed change-related mismatch negativity (MMN) and obligatory P1 and N1 responses in each condition. In the complex condition, the choir singers showed a larger MMN than the controls, which also correlated with better performance in a verbal fluency test. In the simple pitch and location conditions, the choir singers had smaller N1 responses compared to the control subjects, whereas the MMN responses did not differ between groups. These results suggest that regular choir singing is associated both with more enhanced encoding of complex auditory regularities and more effective adaptation to simple sound features.

Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual's academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD. Developmental dyslexia (DD) is the most prevalent neurodevelopmental disorder with a substantial negative influence on the individual's academic achievement and career. Research on its neuroanatomical origins has continued for half a century, yielding, however, inconsistent results, lowered total brain volume being the most consistent finding. We set out to evaluate the grey matter (GM) volume and cortical abnormalities in adult dyslexic individuals, employing a combination of whole-brain voxel- and surface-based morphometry following current recommendations on analysis approaches, coupled with rigorous neuropsychological testing. Whilst controlling for age, sex, total intracranial volume, and performance IQ, we found both decreased GM volume and cortical thickness in the left insula in participants with DD. Moreover, they had decreased GM volume in left superior temporal gyrus, putamen, globus pallidus, and parahippocampal gyrus. Higher GM volumes and cortical thickness in these areas correlated with better reading and phonological skills, deficits of which are pivotal to DD. Crucially, total brain volume did not influence our results, since it did not differ between the groups. Our findings demonstrating abnormalities in brain areas in individuals with DD, which previously were associated with phonological processing, are compatible with the leading hypotheses on the neurocognitive origins of DD.

Nyquist ghost; Denoising; Diffusion Fantasma de Nyquist; Eliminación de ruido; Difusión Fantasma de Nyquist; Eliminació de soroll; Difusió Purpose To develop a robust reconstruction pipeline for EPI data that enables 2D Nyquist phase error correction using sensitivity encoding without incurring major noise artifacts in low SNR data. Methods SENSE with 2D phase error correction (PEC-SENSE) was combined with channel-wise noise removal using Marcenko–Pastur principal component analysis (MPPCA) to simultaneously eliminate Nyquist ghost artifacts in EPI data and mitigate the noise amplification associated with phase correction using parallel imaging. The proposed pipeline (coined SPECTRE) was validated in phantom DW-EPI data using the accuracy and precision of diffusion metrics; ground truth values were obtained from data acquired with a spin echo readout. Results from the SPECTRE pipeline were compared against PEC-SENSE reconstructions with three alternate denoising strategies: (i) no denoising; (ii) denoising of magnitude data after image formation; (iii) denoising of complex data after image formation. SPECTRE was then tested using high -value (i.e., low SNR) diffusion data (up to s/mm ) in four healthy subjects. Results Noise amplification associated with phase error correction incurred a 23% bias in phantom mean diffusivity (MD) measurements. Phantom MD estimates using the SPECTRE pipeline were within 8% of the ground truth value. In healthy volunteers, the SPECTRE pipeline visibly corrected Nyquist ghost artifacts and reduced associated noise amplification in high -value data. Conclusion The proposed reconstruction pipeline is effective in correcting low SNR data, and improves the accuracy and precision of derived diffusion metrics. EPSRC-funded UCL Centre for Doctoral Training in Medical Imaging, Grant/Award Number: EP/L016478/1

Effectiveness of individual- and group-based neuropsychological intervention on aspects of psychological well-being of dyslexic adults was evaluated. Dyslexic young adults (n = 120) were randomly assigned into individual intervention, group intervention or wait-list control group. Both interventions focussed on cognitive strategy learning, supporting self-esteem, and using psychoeducation. In group format peer support was also utilized. Cognitive and behavioural strategies, mood states, quality of life and self-esteem were assessed via self-report questionnaires at baseline, after the intervention/wait-list control time at 5 months and 10 months. Results indicated that the neuropsychological interventions had a positive effect on self-evaluated cognitive and behavioural strategies, especially in increasing success expectations and to a lesser degree in diminishing task-avoidance and in group intervention in diminishing social pessimism. The interventions also improved cognition-related quality of life and, to a lesser degree, self-esteem. These results indicate that structured neuropsychological interventions can positively affect self-evaluated psychological well-being, especially on cognitive and behavioural strategies. Considering the secondary consequences of dyslexia, support among young adults is often needed beyond the cognitive and reading-based challenges dyslexia poses.

Background: Health inequities are already present at birth and affect individuals’ health and socioeconomic outcomes across the life course. Addressing these inequities requires a cross-sectoral approach, covering the first 1,000 days of life. We believe that - in the Dutch context - municipal governments can be the main responsible actor to drive such an approach, since they are primarily responsible for organising adequate public health. Therefore, we aim to identify and develop transformative change towards the implementation of perinatal health into municipal approaches and policies concerning health inequities. Methods: A transition analysis will be combined with action research in six Dutch municipalities. Interviews and interactive group sessions with professionals and organisations that are relevant for the institutional embedding of perinatal health into approaches and policies regarding health inequities, will be organised in each municipality. As a follow-up, a questionnaire will be administered among all participants one year after completion of the group sessions. Discussion: We expect to gain insights into the role of municipalities in addressing perinatal health inequities, learn more about the interaction between different key stakeholders, and identify barriers and facilitators for a cross-sectoral approach to perinatal health. This knowledge will serve to inform the development of approaches to perinatal health inequities in areas with relatively poor perinatal health outcomes, both in the Netherlands and abroad.

Background: Foetal tobacco and cannabis exposure may have persistent cardio-metabolic consequences in the offspring. Objective: We examined the associations of maternal and paternal tobacco and cannabis use during pregnancy with offspring body fat and cardio-metabolic outcomes. Methods: In a population-based prospective cohort study among 4792 mothers, fathers, and children, we assessed parental substance use by questionnaires. Childhood outcomes included body mass index (BMI), body fat, blood pressure, and lipid, glucose and insulin concentrations at 10 years. Results: Children exposed to maternal tobacco use during pregnancy had a higher android/gynoid fat mass ratio (difference 0.22 SDS, 95% confidence interval [CI]: 0.13, 0.30), fat mass index (difference 0.20 SDS, 95% CI: 0.12, 0.28), triglyceride concentrations (difference 0.15 SDS, 95% CI: 0.04, 0.26), and a higher risk of overweight (odds ratio [OR] 1.35, 95% CI: 1.07, 1.71), compared to non-exposed. Children exposed to maternal cannabis during pregnancy had a higher BMI (difference 0.26 SDS, 95% CI: 0.08, 0.44), android/gynoid fat mass ratio (difference 0.21 SDS, 95% CI: 0.04, 0.39), and fat-free mass index (difference 0.24 SDS, 95% CI: 0.06, 0.41), compared to non-exposed. The associations for paternal substance use with child cardio-metabolic health outcomes were similar as those for maternal use. Conclusions: Similar associations for maternal and paternal substance use during pregnancy suggest that these findings may be explained by shared family-based social and lifestyle factors, rather than by direct foetal programming.

Objectives Many older adults with depression do not receive adequate treatment. Differences in treatment utilization may reflect the heterogeneous nature of depression, encompassing multiple distinct symptoms. We assessed whether depressive symptoms are differentially associated with subsequent health care utilization with respect to three outcomes as follows: (1) contact with a medical doctor (MD), (2) depression-specific treatment, and (3) inpatient psychiatric admission. Methods/Design Longitudinal analyses were based on data from three follow-up cycles conducted between 2004 and 2013 among 53,139 participants from the Survey of Health, Aging, and Retirement in Europe. Depressive symptoms were self-reported at baseline of each follow-up cycle using the 12-item EURO-D scale. Health care utilization was self-reported at the end of each follow-up cycle. Results After adjustment for sex, age, country of interview, follow-up time, educational attainment, presence of a partner in household, body-mass index, the number of chronic diseases, disability, average/prior frequency of contact with an MD, and all other depressive symptoms, people with more frequent contact with an MD had most often reported sleep problems (IRR = 1.10) and fatigue (IRR = 1.10), followed by sad/depressed mood, tearfulness, concentration problems, guilt, irritability, and changes in appetite. Those treated for depression had most often reported sad/depressed mood (OR = 2.18) and suicidal ideation (OR = 1.72), but also sleep problems, changes in appetite, fatigue, concentration problems, hopelessness, and irritability. Sad/depressed mood (OR = 2.87) was also associated with psychiatric inpatient admission. Similarly to other outcomes, appetite change, fatigue, and sleep problems were associated with inpatient admission. Conclusions Specific symptoms of depression may determine utilization of different types of health care among elderly.

The interactions of the principal circadian clock with the homeostatic sleep process create the time-sensitive window for easy falling asleep in the evening, which is affected by a thermoregulatory process. It has been hypothesized that the changes in skin and core body temperatures before the sleep onset might play a direct role in sleep regulation. To determine this time window, we recorded from 20 healthy participants (11 women and 9 men), aged 26-58 years, one overnight own-home ambulatory polysomnography and measured continuously wrist skin temperature with a wrist-worn accelerometer containing a skin temperature thermometer. Wrist skin temperatures which were read out from the thermometer of the accelerometers were modeled using linear mixed models, and the linear effect of time before the sleep onset on wrist temperature was analyzed using a mixed model with the sex and age as the covariates. We found that wrist skin temperatures increased on average by 0.6 degrees (of Celcius) in 10 min prior to the sleep onset and could be tracked robustly along a slope of time (p = 0.004). Our current findings may be useful in further characterizing the window of time and its boundaries for easy falling asleep.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Healthcare purchasing organisations in both insurance-based and tax-based healthcare systems struggle to improve chronic care. A key challenge for purchasers is to deal with the chain of multiple providers involved in caring for patients with complex needs. To date, most research has focused on differences between healthcare systems in terms of regulation, tools and the freedom that healthcare purchasers have. However, this does not explain how such different healthcare system characteristics lead to different purchasing strategies and actions. A better understanding of this link between system characteristics and purchaser behaviour would assist policymakers seeking to improve healthcare purchasing. This multiple case study conducted in England, Sweden and the Netherlands examines the link between the different healthcare systems’ characteristics and the purchasers’ strategies and actions when managing chronic care chains. Purchasers’ strategies and actions varied in terms of the purchaser's engagement, strategic lens and influencing style. Our findings suggest that differences in purchaser competition, purchaser governance and patient choice in healthcare systems are key factors in explaining a purchaser's strategies and actions when pursuing improvements in chronic care. This study contributes to knowledge on what shapes the purchaser's role, and shows how policymakers in both insurance- and tax-based regimes can improve healthcare purchasing.

Knowledge on efficient ways to reduce presleep arousal and, therefore, improve sleep, is scanty. We explored the effects of presleep slow breathing and music listening conditions on sleep quality and EEG power spectral density in young adults in a randomized, controlled trial with a crossover design. Participants’ (N = 20, 50% females) sleep was measured on two consecutive nights with polysomnography (40 nights), the other night serving as the control condition. The intervention condition was either a 30-minute slow breathing exercise or music listening (music by Max Richter: Sleep). The intervention and control conditions were placed in a random order. We measured heart rate variability prior to, during and after the intervention condition, and found that both interventions increased immediate heart rate variability. Music listening resulted in decreased N2 sleep, increased frontal beta1 power spectral density, and a trend towards increased N3 sleep was detected. In the slow breathing condition higher central delta power during N3 was observed. While some indices pointed to improved sleep quality in both intervention groups, neither condition had robust effects on sleep quality. These explorative findings warrant further replication in different populations.

Chronotype is the temporal preference for activity and sleep during the 24 h day and is linked to mental and physical health, quality of life, and mortality. Later chronotypes, so-called “night owls”, consistently display poorer health outcomes than “larks”. Previous studies have suggested that preterm birth (

Background This study investigated (i) whether compassion is associated with blood pressure or hypertension in adulthood and (ii) whether familial risk for hypertension modifies these associations. Method The participants (N = 1112–1293) came from the prospective Young Finns Study. Parental hypertension was assessed in 1983–2007; participants’ blood pressure in 2001, 2007, and 2011; hypertension in 2007 and 2011 (participants were aged 30–49 years in 2007–2011); and compassion in 2001. Results High compassion predicted lower levels of diastolic and systolic blood pressure in adulthood. Additionally, high compassion was related to lower risk for hypertension in adulthood among individuals with no familial risk for hypertension (independently of age, sex, participants’ and their parents’ socioeconomic factors, and participants’ health behaviors). Compassion was not related to hypertension in adulthood among individuals with familial risk for hypertension. Conclusion High compassion predicts lower diastolic and systolic blood pressure in adulthood. Moreover, high compassion may protect against hypertension among individuals without familial risk for hypertension. As our sample consisted of comparatively young participants, our findings provide novel implications for especially early-onset hypertension.

Recently, exploring brain activity based on functional networks during naturalistic stimuli especially music and video represents an attractive challenge because of the low signal-to-noise ratio in collected brain data. Although most efforts focusing on exploring the listening brain have been made through functional magnetic resonance imaging (fMRI), sensor-level electro- or magnetoencephalography (EEG/MEG) technique, little is known about how neural rhythms are involved in the brain network activity under naturalistic stimuli. This study exploited cortical oscillations through analysis of ongoing EEG and musical feature during freely listening to music. We used a data-driven method that combined music information retrieval with spatial Fourier Independent Components Analysis (spatial Fourier–ICA) to probe the interplay between the spatial profiles and the spectral patterns of the brain network emerging from music listening. Correlation analysis was performed between time courses of brain networks extracted from EEG data and musical feature time series extracted from music stimuli to derive the musical feature related oscillatory patterns in the listening brain. We found brain networks of musical feature processing were frequency-dependent. Musical feature time series, especially fluctuation centroid and key feature, were associated with an increased beta activation in the bilateral superior temporal gyrus. An increased alpha oscillation in the bilateral occipital cortex emerged during music listening, which was consistent with alpha functional suppression hypothesis in task-irrelevant regions. We also observed an increased delta–beta oscillatory activity in the prefrontal cortex associated with musical feature processing. In addition to these findings, the proposed method seems valuable for characterizing the large-scale frequency-dependent brain activity engaged in musical feature processing., Brain Topography, 33, ISSN:0896-0267, ISSN:1573-6792

Using the concepts and principles of conversation analysis (CA), this paper examines the everyday, unscripted, spontaneous conversations between 4 males who communicated with the aid of speech-output technologies and their mothers. The analyses focused on describing the conversationalists’ various actions in aided turn-transition processes, resulting in a 3-part turn-transition structure used to accomplish aided turn initiation. Despite the challenges to conversational progress, the participants did not consider the conversational speed a challenge. The participants and their mothers were oriented to the progression of the aided conversation by creating interaction practices to achieve successful turn-transitions. By understanding the structural characteristics of fluent aided conversations, it may be possible to develop effective interaction strategies for communication partners and for augmentative and alternative communication technologies that are intentionally designed to facilitate interactive communication.

Introduction: This study used causal mediation analysis to assess the life-course associations of a favorable childhood psychosocial environment with left ventricular mass and diastolic function in adulthood and the extent to which adult health behaviors mediate these associations. Methods: The sample included 880 participants (56% women) from the Young Finns Study with data on the childhood environment from 1980, adult health behaviors (smoking, physical activity, diet, and BMI) from 2001 and an echocardiographic assessment of the left ventricular mass (g/m(2.7)) and diastolic function (E/e' ratio; higher values indicating a lower diastolic function) from 2011. The associations of the childhood environment with the left ventricular mass and E/e' ratio and mediation pathways through health behaviors were assessed using marginal structural models that were controlled for age, sex, and time-dependent confounding by adult socioeconomic position (measured as educational attainment) via inverse probability weighting. The data were analyzed in 2018-2019. Results: The mean age in 2011 was 41 (range 34-49) years. Those above versus below the median childhood score had a 1.28 g/m(2.7) lower left ventricular mass (95% CI = -2.63, 0.07) and a 0.18 lower E/e' ratio (95% CI = -0.39, 0.03). There was no evidence for indirect effects from childhood environments to left ventricular outcomes through adult health behaviors after controlling for time-dependent confounding by the adult socioeconomic position (indirect effect beta = -0.30, 95% CI = -1.22, 0.63 for left ventricular mass; beta = -0.04, 95% CI = -0.18, 0.11 for E/e' ratio). The results after multiple imputation were similar. Conclusions: A favorable childhood environment is associated with more optimal cardiac structure and function in adulthood. After accounting for socioeconomic positions, adult health behaviors explain little of the associations. (C) 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

During sleep, memories are consolidated via oscillatory events that occur in temporal and phasic synchrony. Several studies show that sleep spindles peaking close to the depolarized positive peaks of slow oscillations (SO) associate with better retention of memories. The exact timing of this synchrony presumably depends on the properties of the related neural network that, in turn, is affected by certain genetic variants associated with brain development and function. Brain-derived neurotrophic factor (BDNF) Val66Met and Catechol‐O‐methyltransferase (COMT) Val158Met are repeatedly reported to implicate the structure and function of prefrontal and hippocampal areas as well as molecular events promoting synaptic plasticity. In this study, we examined with a community-based sample of 153 adolescents (~17 years) whether these variants (1) affected the coupling properties between frontal SOs and spindles and (2) moderated the association between SO-spindle coupling and overnight recognition accuracy. We found SO-upstate-coupled fast (> 13 Hz) sleep spindles to associate with better recognition in the whole sample. Additionally, Val66Met moderated this association such that SO-spindle coupling was predictive of memory outcome only in those homozygous to ValBDNF alleles but not in MetBDNF carriers. Memory outcome was not associated with the SO-coupling properties of slow spindles nor affected by the interaction between Val158Met and coupling measures. Finally, in the whole sample we found that SO-upstate-coupled fast spindles were more strongly associated with the recognition of positive, relative to neutral, pictures. In conclusion, precise coupling of SOs and fast spindles associates with overnight recognition accuracy and this association is moderated by BDNF Val66Met.

Background The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs. Materials and methods Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan–Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis. Results Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million. Conclusion Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma., Highlights • The median survival of patients with metastatic melanoma increased from 11.8 months in 2013 to 21.1 months in 2018. • The gain in survival came along with substantial health care costs; health care costs were on average €100 300 per patient. • Costs were much higher for patients with systemic treatment (€118 905) than for patients without systemic treatment (€8316). • Costs for patients who received systemic treatment remained stable even after the introduction of additional novel drugs. • Insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in metastatic melanoma.

Current views on the neural network subserving reading and its deficits in dyslexia rely largely on evidence derived from functional neuroimaging studies. However, understanding the structural organization of reading and its aberrations in dyslexia requires a hodological approach, studies of which have not provided consistent findings. Here, we adopted a whole brain hodological approach and investigated relationships between structural white matter connectivity and reading skills and phonological processing in a cross-sectional study of 44 adults using individual local connectome matrix from diffusion MRI data. Moreover, we performed quantitative anisotropy aided differential tractography to uncover structural white matter anomalies in dyslexia (23 dyslexics and 21 matched controls) and their correlation to reading-related skills. The connectometry analyses indicated that reading skills and phonological processing were both associated with corpus callosum (tapetum), forceps major and minor, as well as cerebellum bilaterally. Furthermore, the left dorsal and right thalamic pathways were associated with phonological processing. Differential tractography analyses revealed structural white matter anomalies in dyslexics in the left ventral route and bilaterally in the dorsal route compared to the controls. Connectivity deficits were also observed in the corpus callosum, forceps major, vertical occipital fasciculus and corticostriatal and thalamic pathways. Altered structural connectivity in the observed differential tractography results correlated with poor reading skills and phonological processing. Using a hodological approach, the current study provides novel evidence for the extent of the reading-related connectome and its aberrations in dyslexia. The results conform current functional neuroanatomical models of reading and developmental dyslexia but provide novel network-level and tract-level evidence on structural connectivity anomalies in dyslexia, including the vertical occipital fasciculus.

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.

Prior research has implicated the medial and lateral prefrontal cortex (PFC) in processing evaluations from the perspective of self (self-traits) and evaluations from others (peer feedback), suggesting that these areas form a neural substrate that serves an intertwined function in monitoring self in relation to others. To test this possibility, we examined neural activation overlap in medial and lateral PFC after processing self- and other-informed evaluations. Young adults (age range 18–30-yrs, n = 40) performed two fMRI tasks. The self-concept task involved rating whether positive and negative traits described themselves. The Social Network Aggression Task involved processing positive, neutral or negative feedback from others, with the possibility to retaliate by blasting a loud noise following feedback. The results show that rating positive self traits and receiving positive peer feedback was associated with increased activity in an overlapping region in medial PFC. There were no significant correlations on a behavioral level and medial PFC activity for self-versus-other evaluations. The study further replicated the finding from previous research showing that higher activity in dorsolateral PFC (dlPFC) when receiving negative social feedback was associated with reduced noise blast aggression. Finally, during retaliatory responses after receiving positive feedback, participants showed increased activity in the dlPFC. Together these findings suggest that medial PFC is more strongly involved in protecting positive self-views from both internal (self traits) and external (peer feedback) points of view, whereas dlPFC is more strongly involved in regulating retaliatory responses following social rejection, and actively inhibiting aggressive behavior after receiving positive peer feedback.

Youth of today grow up in a digital social world but the effects on well-being and brain development remain debated. This study tracked longitudinal associations between structural brain development, social media use and mental well-being. The study demonstrated two pathways of heterogeneity in brain development. First, adolescents who used social media more than their peers showed higher baseline cortical thickness in lateral prefrontal cortex (PFC) and medial PFC; and stronger decreases in the lateral PFC and temporal parietal junction. In contrast, adolescents with lower mental well-being showed lower baseline levels of surface area in the medial PFC and posterior superior temporal sulcus relative to their peers. Whereas the associations between structural brain development and well-being remained significant after correction for multiple testing, the results for social media use did not survive FDR correction. These findings demonstrate that although social media use and mental well-being were both associated with differential trajectories of brain development, the associations we report are distinct. These results show a nuanced perspective on the presumed relations between social media use and well-being and provide a starting point to further examine neural mechanisms that could explain which adolescents thrive by social media and which might be harmed.

Objective Individuals with low socioeconomic status have higher rates of depression, but it is unknown whether the socioeconomically disadvantaged also have more disabling depressive symptoms. We examined (1) the associations of three indicators of socioeconomic status with depression-related severe role impairment, and (2) whether socioeconomic factors moderate the association between individual depression symptoms and depression-related severe role impairment. Methods We used data from the National Survey on Drug Use and Health (NSDUH). Depressive symptoms, role impairment and socioeconomic indicators (poverty, participation in workforce, educational attainment) were self-reported by participants. The analytic sample consisted of participants who screened positive for a depressive episode during past 12 months (n = 32 661). We used survey-weighted logistic models to examine the associations of depressive symptoms with severe role impairment and the modifying effects of socioeconomic indicators. Results The association between depression symptom count and severe role impairment was stronger among those not in workforce (OR = 1.12[1.02–1.23]). The association between specific depression symptoms and severe role impairment was stronger for conditions of poverty (fatigue, OR = 2.97 [1.54–5.73]; and anhedonia, OR = 1.93[1.13–3.30]), workforce non-participation (inability to concentrate/indecisiveness, OR = 1.54[1.12–2.12]), and lower educational attainment (anhedonia, OR = 0.77 [0.59–0.99]). Feelings of worthlessness was the only symptom with independent associations for all socioeconomic groups (adjusted OR = 1.91[1.35–2.70]). Conclusion Depression was more frequent and also more disabling for socioeconomically disadvantaged groups, especially when assessed with workforce participation. Additionally, some specific symptoms showed socioeconomic differences. Our findings highlight the need to prioritize population groups with more severe impairment associated with depressive symptoms.

Background The role of domain-general short-term memory (STM) in language development remains controversial. A previous finding from the HelSLI study on children with developmental language disorder (DLD) suggested that not only verbal but also non-verbal STM for temporal order is related to language acquisition in monolingual children with DLD. Aims To investigate if a similar relationship could be replicated in a sample of sequentially bilingual children with DLD. In addition to the effect of age, the effect of cumulative second language (L2) exposure was studied. Methods & Procedures Sixty-one 4-6-year-old bilingual children with DLD and 63 typically developing (TD) bilingual children participated in a cross-sectional study conducted in their L2. Children completed novel game-like tests of visual and auditory non-verbal serial STM, as well as tests of cognitive functioning and language. Interactions of STM for order with age and exposure to L2 (Finnish) were explored as explanatory variables. Outcomes & Results First, the improvement of non-verbal serial STM with age was faster in sequentially bilingual TD children than in bilingual children with DLD. A similar effect was observed for L2 exposure. However, when both age and exposure were considered simultaneously, only age was related to the differential growth of non-verbal STM for order in the groups. Second, only in children with DLD was better non-verbal serial STM capacity related to an improvement in language scores with age and exposure. Conclusions & Implications The results suggest that, as previously found in Finnish monolingual children, domain-general serial STM processing is also compromised in bilingual children with DLD. Further, similar to the monolingual findings, better non-verbal serial STM was associated with greater language improvement with age and exposure, but only in children with DLD, in the age range studied here. Thus, in clinical settings, assessing non-verbal serial STM of bilingual children could improve the detection of DLD and understanding of its non-linguistic symptoms. What this paper adds What is already known on the subject Both phonological and non-verbal STM have been associated with DLD in monolingual and sequentially bilingual children. Monolingual children with DLD have also shown slower non-verbal serial STM development than TD children. What this study adds to existing knowledge Sequentially bilingual TD children's non-verbal serial STM improves more between ages 4 and 7 years than that of their peers with DLD, replicating a finding for monolingual children with DLD. Better non-verbal serial STM was especially associated with early receptive language development in sequentially bilingual children with DLD. L2 exposure showed largely comparable effects with age. These results support the hypothesis that a domain-general serial STM deficit is linked to DLD. What are the potential or actual clinical implications of this work? Non-verbal assessment of STM for serial order in sequentially bilingual children with DLD could benefit the development of better tailored therapeutic interventions.

Musical activities have been suggested to be beneficial for language development in childhood. Randomised controlled trials using music have indicated that musical interventions can be used to support language skills in children with developmental language difficulties. However, it is not entirely clear how beneficial music activities are for normally developing children or how the effects mediated via music are transmitted. To investigate these questions, the present study used structural equation models to assess how musical training, perceptual musical skills, and auditory processing in the brain are associated with reading proficiency and each other. Perceptual musical skills were assessed using musicality tests while auditory processing in the brain was measured using mismatch negativity responses to pitch, duration, and phoneme length contrasts. Our participants were a community sample of 64 8–11-year-old typically developing children with and without musical training, recruited from four classes in four elementary schools in Finland. Approximately half of children had music as a hobby. Our results suggest that performance in tests of musical perceptual skills is directly linked with reading proficiency instead of being mediated via auditory processing in the brain. Auditory processing in the brain in itself seems not to be strongly linked with reading proficiency in these children. Our results support the view that musical perceptual skills are associated with reading skills regardless of musical training.

According to the network theory strong associations between symptoms drive the disease process. We compared those with and without diagnosed depressive disorders (DD+/DD-) and analysed the effects of differences in (a) network connectivity, (b) symptom thresholds, and (c) autoregressive loops (i.e. how strongly specific symptoms predict themselves) on the potential activation of symptoms over time using simulations developed by Cramer and others (2016). The parameters for the simulation (symptom connectivity and symptom threshold) were obtained from Ising models and cross-lagged panel network analyses. Data were from the nationally representative samples (Health 2000-2011 Study) of 4190 participants measured in 2011 (cross-sectional analyses) and 3201 participants measured in 2000 and 2011 (longitudinal analyses). DD diagnosis was based on the Composite International Diagnostic Interview and depressive symptoms were self-reported using the 13-item version of the Beck Depression Inventory (BDI). Differences in symptom connectivity between participants with and without DD were not observed, but the mean probability (threshold) of symptom existence in the DD + group was higher than in the DD-group (0.41 vs. 0.12). Simulation showed that there are more active symptoms in the DD + group after 10 000 time points (means 1.2 vs. 4.6) than in the DD-group. This difference largely disappeared when we used longitudinal networks, including autoregressive loops, in the connectivity matrix. Our results suggest that the differences in symptom thresholds and autoregressive loops may be more important features than symptom connectivity in differentiating people with and without DD.

Aim\ud To describe motor development in preschool children, to identify perinatal, neonatal, and social environmental risk factors of poor motor development, and to replicate results in a second cohort.\ud \ud Methods\ud Two prospective samples in Germany (Bavarian Longitudinal Study, BLS) and Finland (Arvo Ylppö Longitudinal Study, AYLS) assessed 4,741 and 1,423 children from birth to 56 months, respectively. Motor functioning was evaluated at birth, and 5, 20 and 56 months. Perinatal, neonatal and social environmental information was collected at birth and 5 months.\ud \ud Results\ud Two distinct motor trajectories were identified: low (BLS: n=4,486 (94.6%), AYLS: n=1,391 (97.8%)) and high (BLS: n=255 (5.4%), AYLS: n=32 (2.2%)) degree of motor difficulties. High degree of motor difficulties was predicted by neonatal complications, abnormal neonatal neurological status, duration of hospitalisation, and poor parent‐infant relationships. Although neonatal complications and poor parent‐infant relationships did not significantly predict high degree of motor difficulties in the AYLS, the trends identified were similar to those obtained from the BLS.\ud \ud Conclusion\ud Early identification of children at‐risk of motor difficulties across infancy and toddlerhood may help referring those children to interventions earlier. Modifiable risk factors, such as parent‐infant relationships, may be addressed by intervention strategies to prevent children from developing motor difficulties.

International audience; The mismatch negativity (MMN) is an event related brain potential (ERP) elicited by unpredicted sounds presented in a sequence of repeated auditory stimuli. The neural sources of the MMN have been previously attributed to a fronto-temporo-parietal network which crucially overlaps with the so-called auditory dorsal stream, involving inferior and middle frontal, inferior parietal, and superior and middle temporal regions. These cortical areas are structurally connected by the arcuate fasciculus (AF), a three-branch pathway supporting the feedback-feedforward loop involved in auditory-motor integration, auditory working memory, storage of acoustic templates, as well as comparison and update of those templates. Here, we characterized the individual differences in the white-matter macrostructural properties of the AF and explored their link to the electrophysiological marker of passive change detection gathered in a melodic multifeature MMN-EEG paradigm in 26 healthy young adults without musical training. Our results show that left fronto-temporal white-matter connectivity plays an important role in the pre-attentive detection of rhythm modulations within a melody. Previous studies have shown that this AF segment is also critical for language processing and learning. This strong coupling between structure and function in auditory change detection might be related to life-time linguistic (and possibly musical) exposure and experiences, as well as to timing processing specialization of the left auditory cortex. To the best of our knowledge, this is the first time in which the relationship between neurophysiological (EEG) and brain white-matter connectivity indexes using DTI-tractography are studied together. Thus, the present results, although still exploratory, add to the existing evidence on the importance of studying the constraints imposed on cognitive functions by the underlying structural connectivity.

Conservative political ideologies have been suggested to correlate with elevated sensitivity to threat. However, it is unclear whether the associations between threat sensitivity and political attitudes can be observed with clinical measures of mental health. We examined how anxiety disorders predicted attitudes on several political issues. Participants were 7253 individuals from the 1958 British Birth Cohort study. Symptoms of generalised anxiety disorder, phobia and panic were assessed in a clinical interview at age 44, and opinions about political issues were self-reported by the participants 6 years later. Anxiety symptoms were associated with higher concerns about economic inequality, preservation of the environment, distrust in politics and lower work ethic. No associations were observed with racist or authoritarian attitudes, or support for traditional family values. We also assessed how political attitudes at ages 33 and 42 predicted anxiety disorder symptoms at age 44, revealing a possible bidirectional association between concern for economic inequality and anxiety disorder symptoms. These findings do not support an association between conservative political attitudes and elevated threat sensitivity. Rather, elevated anxiety may increase concerns about social inequality and the environment.

MRI studies have provided valuable insights into the structure and function of neural networks, particularly in health and in classical neurodegenerative conditions such as Alzheimer disease. However, such work is also highly relevant in other diseases of the CNS, including multiple sclerosis (MS). In this Review, we consider the effects of MS pathology on brain networks, as assessed using MRI, and how these changes to brain networks translate into clinical impairments. We also discuss how this knowledge can inform the targeting of MS treatments and the potential future directions for research in this area. Studying MS is challenging as its pathology involves neurodegenerative and focal inflammatory elements, both of which could disrupt neural networks. The disruption of white matter tracts in MS is reflected in changes in network efficiency, an increasingly random grey matter network topology, relative cortical disconnection, and both increases and decreases in connectivity centred around hubs such as the thalamus and the default mode network. The results of initial longitudinal studies suggest that these changes evolve rather than simply increase over time and are linked with clinical features. Studies have also identified a potential role for treatments that functionally modify neural networks as opposed to altering their structure.

Objectives: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age, final draft, peerReviewed

Grit has recently been challenged for its weak predictive power and the incompleteness of its measurement. This study addressed these issues by taking a developmental, person-oriented approach to study academic-related goal commitment and grit and their effects on academic achievement. Using longitudinal data among Finnish eighth and ninth graders (n = 549, 59.4% female, age = 14–16), the longitudinal changes in grit and academic goal commitment profiles were investigated through latent profile and latent transition analyses. Four profiles were identified across two grades: High committed-persistent and moderate consistency (~17%), Moderate (~60%), Low committed-persistent and moderate-low consistency (~8%) and Extremely low committed-persistent and moderate-low consistency (~12%). The students in the High committed-persistent and moderate consistency profile had the highest academic achievement of all the profiles when controlled for gender, socioeconomic status, conscientiousness, and academic persistence. The results revealed that students’ profiles changed between the eighth and ninth grades, with more than one-third of the High committed-persistent and moderate consistency adolescents dropping from this group. Further analysis showed that the profiles varied by educational aspiration, gender, and socioeconomic status. These findings imply that the combination of grit and academic goal commitment influences academic achievement; however, this combination is less common, unstable, and affected by internal and external factors. The study provided important implications on the weak grit effect and the ways to improve it.

Background The aims of this study were to (1) compare differences in psychiatric comorbidity of depression and anxiety disorders between immigrants and native Finns and to (2) compare differences in the intensity of psychiatric care received by different immigrant groups and Finnish-born controls with depression and/or anxiety disorders. Methods The study uses registered-based data, which includes all immigrants living in Finland at the end of 2010 and matched Finnish-born controls. For this study, we selected individuals who had received a diagnosis of depression and/or an anxiety disorder during the follow-up (2011–2015) (immigrants n = 6542, Finnish-born controls n = 9281). We compared differences in comorbidity between the immigrants and the Finnish-born controls using chi-squared tests. Multinomial logistic regression was used to predict psychiatric treatment intensity by immigrant status, region of origin, and other background factors. Results In both diagnosis groups, Finnish-born participants exhibited greater comorbidity of other psychiatric disorders. Immigrants more often received lower intensity treatment and less often higher intensity treatment. These differences were most striking among those from Eastern Europe, the Middle East, and Africa. Limitations We did not have the information on the perceived need for the services, which limits us from drawing further conclusions about the mechanisms behind the observed patterns. Conclusions Immigrants in Finland receive less intensive treatment for depression and anxiety disorders compared to the Finnish-born population. Since lower symptom levels can unlikely alone explain these differences, they could reflect a need for improvement in the psychiatric services for immigrants.

This article introduces key concepts of activity theory and expansive learning. Expansive learning builds on the foundational ideas of the cultural-historical activity theory (CHAT). It is a research approach designed for studying the complexities and contradictions in authentic workplace environments. Change Laboratory is a formative intervention method developed for studying workplaces in transition and for stimulating collaborative efforts to design improved patterns of activity. We present concrete examples of formative interventions in healthcare, where good patient care was compromised by the fragmentation of care and disturbances in collaboration between the healthcare experts. This implies that physicians are challenged to develop collaborative and transformative expertise. We present three spearheads into a zone of proximal development, representing opportunities for change of medical expertise: (1) reconceptualizing expertise as object-oriented and contradiction-driven activity systems, (2) pursuing expertise as negotiated knotworking, and (3) building expertise as expansive learning. While medical expertise needs to expand, medical education must also look for ways to evolve and meet the challenges of the surrounding society. We call for adopting an interventionist approach for developing medical education and intensifying collaboration with the practitioners in healthcare units, their patients, and target communities.

Purpose of ReviewWe review here recent original research and meta-analytic evidence on the associations of maternal hypertensive pregnancy disorders and mental and behavioral disorders in the offspring.Recent FindingsSeven meta-analyses and 11 of 16 original research studies published since 2015 showed significant associations between maternal hypertensive pregnancy disorders and offspring mental and behavioral disorders. Evidence was most consistent in meta-analyses and high-quality cohort studies. The associations, independent of familial confounding, were observed on different mental and behavioral disorders in childhood and schizophrenia in adulthood. Preterm birth and small-for-gestational age birth emerged as possible moderators and mediators of the associations. Cross-sectional and case-control studies yielded inconsistent findings, but had lower methodological quality.SummaryAccumulating evidence from methodologically sound studies shows that maternal hypertensive pregnancy disorders are associated with an increased risk of mental and behavioral disorders in the offspring in childhood. More studies on adult mental disorders are needed.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

DAL’s contribution to this paper is supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC grant agreement no 669545) and a UK National Institute of Health Senior Investigator (NF-0616-10102). TC’s contribution is supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle). MLV has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707404. The opinions expressed in this document refect only the author’s view. The European Commission is not responsible for any use that may be made of the information it contains. The INfancia y Medio Ambiente (INMA)-Sabadell cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; CP18/00018; PI041436; PI081151; PI1100610 incl. FEDER funds). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S). SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). JJ holds Miguel Servet-II contract (CPII19/00015) awarded by the Instituto de Salud Carlos III (Co-funded by European Social Fund “Investing in your future”). MC holds a Miquel ServetI cotract (CP16/00128) awarded by the Instituto de Salud Carlos III (co-funded by European Social Fund "Investing in your future"). The INMA-Asturias cohort is funded by grants from Instituto de Salud Carlos III (FISS PI 04/2018, FISS PI09/02311, FISS PI13/02429, FISS PI18/00909 including FEDER funds) and University of Oviedo. This study was funded by Instituto de Salud Carlos III through the projects ‘CP14/00108 & PI16/00261’ (co-funded by European Regional Development Fund ‘A way to make Europe’) (…), Alemany, S., Avella-García, C., Liew, Z., García-Esteban, R., Inoue, K., Cadman, T., López-Vicente, M., González, L., Riaño Galán, I., Andiarena, A., Casas, M., Margetaki, K., Strandberg-Larsen, K., Lawlor, D.A., El Marroun, H., Tiemeier, H., Iñiguez, C., Tardón, A., Santa-Marina, L., Júlvez, J., Porta, D., Chatzi, L., Sunyer, J.

Object We investigated the impact of a school-based 9-week mindfulness program vs. active control program (relaxation) and inactive control group on children’s self-reported Health-Related Quality of Life (HRQoL) moderated by gender, grade, and independent practice. Method In total 3519 (50/50% boys/girls) Finnish students aged 12–15 years from 56 schools were randomized into mindfulness intervention, active, and inactive control groups. HRQoL was measured at baseline, at 9 weeks, and at 26 weeks and analyzed with multilevel linear modeling. Results Significant improvement on HRQoL was found (β = mean difference) (β = 1.587, 95% CI 0.672–2.502, p Conclusions Gender and developmental stage may moderate the effects of mindfulness interventions on HRQoL and offer guidance in designing effective promotive interventions for children and adolescents. Trial Registration Information Healthy Learning Mind—a school-based mindfulness and relaxation program: a study protocol for a cluster randomized controlled trial (RCT) ISRCTN18642659 retrospectively registered on 13 October 2015. The full trial protocol can be accessed at http://rdcu.be/t57S.

Traumatic brain injury (TBI) is characterized by a complex pattern of abnormalities in resting-state functional connectivity (rsFC) and network dysfunction, which can potentially be ameliorated by rehabilitation. In our previous randomized controlled trial, we found that a 3-month neurological music therapy intervention enhanced executive function (EF) and increased grey matter volume in the right inferior frontal gyrus (IFG) in patients with moderate-to-severe TBI (N=40). Extending this study, we performed longitudinal rsFC analyses of resting-state fMRI data using a ROI-to-ROI approach assessing within-network and between-network rsFC in the frontoparietal (FPN), dorsal attention (DAN), default mode (DMN), and salience (SAL) networks, which all have been associated with cognitive impairment after TBI. We also performed a seed-based connectivity analysis between the right IFG and whole-brain rsFC. The results showed that neurological music therapy increased the coupling between the FPN and DAN as well as between these networks and primary sensory networks. By contrast, the DMN was less connected with sensory networks after the intervention. Similarly, there was a shift towards a less connected state within the FPN and SAL networks, which are typically hyperconnected following TBI. Improvements in EF were correlated with rsFC within the FPN and between the DMN and sensorimotor networks. Finally, in the seed-based connectivity analysis, the right IFG showed increased rsFC with the right inferior parietal and left frontoparietal (Rolandic operculum) regions. Together, these results indicate that the rehabilitative effects of neurological music therapy after TBI are underpinned by a pattern of within- and between-network connectivity changes in cognitive networks as well as increased connectivity between frontal and parietal regions associated with music processing.

Cognitive decline is evident in the elderly and it affects speech perception and foreign language learning. A listen-and-repeat training with a challenging speech sound contrast was earlier found to be effective in young monolingual adults and even in advanced L2 university students at the attentive and pre-attentive levels. This study investigates foreign language speech perception in the elderly with the same protocol used with the young adults. Training effects were measured with attentive behavioural measures (N = 9) and with electroencephalography measuring the pre-attentive mismatch negativity (MMN) response (N = 10). Training was effective in identification, but not in discrimination and there were no changes in the MMN. The most attention demanding perceptual functions which benefit from experience-based linguistic knowledge were facilitated through training, whereas pre-attentive processing was unaffected. The elderly would probably benefit from different training types compared to younger adults.

The development of treatments for attention impairments is hampered by limited knowledge about the malleability of underlying neural functions. We conducted the first randomized controlled trial to determine the modulations of brain activity associated with working memory (WM) training in adults with attention‐deficit hyperactivity disorder (ADHD). At baseline, we assessed the aberrant functional brain activity in the n‐back WM task by comparing 44 adults with ADHD with 18 healthy controls using fMRI. Participants with ADHD were then randomized to train on an adaptive dual n‐back task or an active control task. We tested whether WM training elicits redistribution of brain activity as observed in healthy controls, and whether it might further restore aberrant activity related to ADHD. As expected, activity in areas of the default‐mode (DMN), salience (SN), sensory‐motor (SMN), frontoparietal (FPN), and subcortical (SCN) networks was decreased in participants with ADHD at pretest as compared with healthy controls, especially when the cognitive load was high. WM training modulated widespread FPN and SN areas, restoring some of the aberrant activity. Training effects were mainly observed as decreased brain activity during the trained task and increased activity during the untrained task, suggesting different neural mechanisms for trained and transfer tasks., We conducted the first randomized controlled trial to determine the modulations of brain activity associated with working memory (WM) training in adults with attention‐deficit hyperactivity disorder. WM training modulated widespread areas in the frontoparietal and salience networks, restoring some of the aberrant activity. Training effects were mainly observed as decreased brain activity during the trained task and increased activity during the untrained task, suggesting different neural mechanisms for trained and transfer tasks.

Objective Associations of eveningness with health hazards benefit from analyzing to what extent the polygenic score for morningness correlates with the assessments of the behavioral trait of morningness-eveningness and chronotype. Methods With a population-based sample of 17,243 Finnish adults, aged 25–74 years, this study examines the associations of four feasible assessment methods of chronotype, a) biological the genetic liability based on the polygenic score for morningness (PGSmorn), b) the widely-used single item for self-assessed morningness/eveningness (MEQi19) of the original Morningness-Eveningness Questionnaire (MEQ), c) the behavioral trait of morningness-eveningness as assessed with the score on the shortened version (sMEQ) of the original MEQ, and d) the phase of entrainment as assessed with the habitual midpoint of sleep based on the self-reported sleep-wake schedule during weekend (Sleepmid-wknd) as well as the sleep debt corrected midpoint of sleep (Sleepmid-corr). Results All self-report measures correlated with each other, but very weakly with the PGSmorn, which explained 1–2% of the variation in diurnal preference or habitual sleep-wake schedule. The influence of age was greater on Sleepmid-wknd and Sleepmid-corr than on the sMEQ or MEQi19, indicating that the diurnal preference might be a more stable indicator for morningness-eveningness than the sleep-wake schedule. Analyses of the discrepancies between sMEQ and MEQi19 indicated that eveningness can be over-estimated when relying on only the single-item self-assessment. Conclusions The current polygenic score for morningness explains only a small proportion of the variation in diurnal preference or habitual sleep-wake schedule. The molecular genetic basis for morningness-eveningness needs further elucidation.

Background and objectives Schema group therapy is a potentially cost-effective treatment for borderline personality disorder (BPD). We piloted the feasibility and effectiveness of a 20-session schema group therapy without individual therapy among psychiatric BPD outpatients in a randomized pilot study registered as a clinical trial (ISRCTN76381242). Methods Altogether 42 psychiatric outpatients diagnosed with BPD were randomized 2:1 to a 20-session weekly schema group therapy plus treatment as usual (TAU) (n = 28) vs. a control group with TAU alone (n = 14). The primary outcome was decline of BPD symptoms in the short Borderline Symptom List (BSL-23) score. Secondary outcomes were decline in symptoms of anxiety, depression, alcohol use, and improvement in functioning and schema modes. Two external experts evaluated validity of the intervention based on videotaped sessions. Results Overall, 23 schema group therapy patients (82%) and 12 controls (86%) completed their treatment. Treatment validity good or very good. However, no significant differences emerged in the primary outcome mean BSL-23 decline (6.95 [SE 5.91] in group schema therapy vs. 12.55 [4.85] in TAU) or in any of the secondary outcome measures. Limitations Despite randomization, the TAU subgroup had non-significantly higher baseline scores in most measures. Small sample size predisposing to type II errors; reliance on self-reported outcomes. Conclusions Schema group therapy was feasible for psychiatric outpatients with BPD. However, in this small pilot study we did not find it more effective than TAU. Effectiveness of this short intervention remains open.

Background: Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms. Methods: About 742 women from the prospective Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds. Results: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%–1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%–88.0%). Further, the polygenic risk scores were associated with 1.24–1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods. Conclusions: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions.

International audience; This study used event-related potential (ERP) measurements to investigate whethererror processing in a social context is modulated by top-down influence of deterministic thinking, i.e., subjective beliefs that events are pre-determined by previously existing causes. To this end, half of our participants were confronted withstatements denying the existence of free will, aimed to induce more deterministicthinking, whereas the other half was assigned to a control group that read neutralstatements. Thereafter, all participants performed a choice-reaction task for theirown and for the benefit of a second participant. Error rates were comparable in bothgroups and benefit settings, while only control participants showed enhanced posterror slowing (PES) in other- compared to self-relevant trials. On the neural level,other-relevant errors elicited diminished early error signals (reduced ΔERN amplitudes) in deterministic-intervention participants compared to controls. In subsequentprocessing, ERPs of deterministic-intervention participants did not differentiate between the benefit settings, while controls showed reduced ΔPe amplitudes for others compared to self-relevant errors. Taken together, our findings suggest that beingconfronted with deterministic compared to control statements reduced subsequentprocessing differences between other- and self-relevant error processing. This mightbe beneficial in social evaluation or intergroup situations because it could decreaseself-cenetred processing biases often observed in these situations.

Background The objective of this study was to examine how nonverbal skills at age five years relate to visual perception and brain activation during visual perception tasks at age 12 years in very preterm subjects without visual or other neurodevelopmental impairments or major brain pathologies. Methods At age five years, 36 prematurely born (birth weight ≤1500 g or gestational age less than 32 weeks) and 31 term-born control children were assessed with the nonverbal subtests of the Wechsler Preschool and Primary Scale of Intelligence-Revised and the NEPSY-Second Edition. At age 12 years the same children were re-assessed with tasks from the Motor-Free Visual Perception Test, Third Edition, during functional magnetic resonance imaging. Results Test performance at age five years was significantly poorer in the very preterm group than the control subjects, but at age 12 years performance was similar in both groups. In the very preterm group, better nonverbal skills at age five years were significantly associated with stronger neural activation during the visual perception task at age 12 years. No associations between nonverbal skills at age five years and brain activation at age 12 years appeared in the control group. Conclusions The associations between better nonverbal skills and stronger neural activation during visual perception task only observed in the very preterm group may reflect delayed development of the visual perception network and/or prematurity-related neural plasticity. The developmental follow-up of very preterm children should include psychological assessment of nonverbal skills at least until age five years.