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Objective: This study tested two opposing hypotheses on the continuity of psychopathology throughout adolescence and young adulthood; differentiation versus dynamic mutualism. Differentiation predicts that co-occurrence decreases, while dynamic mutualism predicts that co-occurrence increases due to causal interactions amongst mental health problems., Method: Using data from the Dutch TRacking Adolescents' Individual Lives Survey (n = 2228, 51% female), we studied the development of self-reported internalizing, externalizing, and attention problems at ages 11 to 26 across six waves. Random-intercept cross-lagged panel modeling was employed to distinguish within-person development from stable between-person processes., Results: Large stable between-person associations indicated that adolescents with internalizing problems tended to have both externalizing and attention problems as well. On a within-person level, mental health problems showed partial stability and strong cross-sectional co-occurrence. Within-wave associations of internalizing with externalizing or attention problems decreased between age 11 and 16 years, after which they increased again. Little heterotypic continuity was found: age 11 externalizing predicted age 13 attention, which in turn predicted age 16 externalizing problems, and internalizing predicted externalizing problems across ages 22 to 26. Findings were similar for males and females., Conclusions: Our findings suggest co-occurrence decreases during early and middle adolescence, supporting differentiation. While co-occurrence increased again into young adulthood, this could not be labeled as dynamic mutualism because little evidence for heterotypic continuity was found in this phase of life. The strong stable links between internalizing, externalizing, and attention problems stress the importance of targeting these mental health problems and their shared risk factors together.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development., (© 2023. The Author(s).)

Background: Psychopathology has been long recognized as a fluctuating process with various expressions over time, which can only be properly understood if we follow individuals and their social context from childhood up until adulthood. Longitudinal population-based studies have yielded powerful data to analyze this process. However, the resulting publications have not been reflected upon with regard to (a) the homotypic and heterotypic stability of internalizing and externalizing problems and (b) how transactions between psychopathology and environmental factors shape its development., Methods: In this narrative review, we primarily focused on population-based studies that followed cohorts repeatedly from an early age (<18 years) onwards, across multiple stages of development, using statistical methods that permit inferences about within-person bidirectional associations between internalizing and externalizing problems or psychopathology-environment transactions., Results: There is robust evidence that mental health problems in childhood or adolescence predict psychiatric problems later in development. In terms of the broadband domains internalizing and externalizing problems, homotypic stability greatly exceeds heterotypic stability and transitions from purely internalizing to purely externalizing problems or vice versa are rare. Homotypic rank-order stabilities seem to increase over time. Findings regarding transactions with environmental factors are less robust, due to widely varying research topics and designs, and a scarcity of studies that separated between-person differences from within-person changes. In general, however, the literature shows little consistent evidence for substantial mutual prospective influences between psychopathology and environmental factors., Conclusions: Longitudinal surveys have strongly augmented insight into homotypic and heterotypic stability and change. Attempts to unravel the myriad of risk and protective factors that place individuals on particular pathways or deflect them from these pathways are still in a pioneering phase and have not yet generated robust findings. As a way forward, we propose to join forces and develop a common risk factor taxonomy., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

The social defeat hypothesis of schizophrenia, which proposes that the chronic experience of outsider status or subordinate position leads to increased striatal dopamine activity and thereby to increased risk, has been criticized. The aims of this paper are to improve the definition of defeat and to integrate the social defeat hypothesis with the neurodevelopmental hypothesis. Marmot advanced the idea that low status is pathogenic in that it is associated with a lack of social participation and a lack of autonomy. Given the similarity with outsider status and subordinate position, we re-define social defeat as low status. From this new perspective it is also likely that pre-schizophrenic impairments (of neurodevelopmental origin or not) are pathogenic in that they contribute to low status. The effect of low status may be enhanced by repeated exposure to humiliation, but few studies have measured this variable. Since most individuals exposed to low status do not develop schizophrenia, we propose that this risk factor increases the risk of disorder in the presence of a poor homeostatic control of dopamine neurons in midbrain and dorsal striatum. This is consistent with studies of healthy subjects which report a negative association between low socio-economic status and dopamine D2/D3 receptor availability in the dorsal striatum. In this new version of the social defeat hypothesis we propose that the combination of low status, repeated humiliation and poor homeostatic control of dopamine neurons in midbrain and dorsal striatum leads to increased striatal dopamine activity and thereby to an increased risk of schizophrenia.

Few investigations have directly compared personality and internalizing symptoms stability within the same sample and have not included personality facets. This study examined rank-order stability and mean-level change of Big Five domains, facets of neuroticism and extraversion, and internalizing symptoms in a sample of 550 adolescent females. Personality and symptoms were assessed every nine months for three years. Three year rank-order stability was higher for personality domains and facets compared to symptoms. Notable exceptions included lower stability of depressivity and positive emotionality facets. Facets and symptoms showed similar mean level change. Overall, we observed modest and variable temporal differences between symptoms and traits; symptoms exhibited high rank-order stability and low mean-level change, but domains and facets were generally more stable.

Treatments for depression have improved, and their availability has markedly increased since the 1980s. Mysteriously the general population prevalence of depression has not decreased. This "treatment-prevalence paradox" (TPP) raises fundamental questions about the diagnosis and treatment of depression. We propose and evaluate seven explanations for the TPP. First, two explanations assume that improved and more widely available treatments have reduced prevalence, but that the reduction has been offset by an increase in: 1) misdiagnosing distress as depression, yielding more "false positive" diagnoses; or 2) an actual increase in depression incidence. Second, the remaining five explanations assume prevalence has not decreased, but suggest that: 3) treatments are less efficacious and 4) less enduring than the literature suggests; 5) trial efficacy doesn't generalize to real-world settings; 6) population-level treatment impact differs for chronic-recurrent versus non-recurrent cases; and 7) treatments have some iatrogenic consequences. Any of these seven explanations could undermine treatment impact on prevalence, thereby helping to explain the TPP. Our analysis reveals that there is little evidence that incidence or prevalence have increased as a result of error or fact (Explanations 1 and 2), and strong evidence that (a) the published literature overestimates short- and long-term treatment efficacy, (b) treatments are considerably less effective as deployed in "real world" settings, and (c) treatment impact differs substantially for chronic-recurrent cases relative to non-recurrent cases. Collectively, these a-c explanations likely account for most of the TPP. Lastly, little research exists on iatrogenic effects of current treatments (Explanation 7), but further exploration is critical., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Heterogeneity in development of imbalance between impulse control and sensation seeking has not been studied until now. The present study scrutinized this heterogeneity and the link between imbalance and adolescent risk. Seven-wave data of 7,558 youth (50.71% males; age range from 12/13 until 24/25) were used. Three developmental trajectories were identified. The first trajectory, "sensation seeking to balanced sensation seeking", included participants with a higher level of sensation seeking than impulse control across all ages. The second trajectory, "moderate dominant control", included participants showing moderate and increasing impulse control relative to sensation seeking across all ages. The third trajectory, "strong late dominant control", included participants showing the highest level of impulse control which was about as strong as sensation seeking from early to middle adolescence and became substantially stronger from late adolescence to early adulthood. Although the systematic increase of impulse control in all subgroups is in line with both models, neither of these combined trajectories of control and sensation seeking was predicted by the Dual Systems Model or the Maturational Imbalance Model. Consistent with both models the "sensation seeking to balanced sensation seeking" trajectory showed the highest level of substance use. It can be concluded that, even though both theories adequately predict the link between imbalance and risk, neither the Dual Systems Model nor the Maturational Imbalance Model correctly predict the heterogeneity in development of imbalance between impulse control and sensation seeking.

Large increases in treatment of Common Mental Disorders (CMD) have failed to reduce population prevalence and global burden. Preventive strategies are needed to lower CMD prevalence and burden. Giving prevention a real chance to prove its promise will require: (a) full embedment in social institutions; (b) long-term structural funding; (c) targeting major CMD determinants early in life combining population-level and individual-level strategies; and, (d) integrated evaluation of short-term and long-term effects to guide implementation. Targeting life skills and resilience of children and parenting skills of their parents has the potential for long-term benefits for multiple outcomes including well-being, social, economic, and financial domains as well as mental health outcomes. However, the large investments may not occur without compelling proof of effectiveness, but evaluation of effectiveness cannot occur without long-term, structural investments. Overcoming this impasse requires a paradigm shift. Randomized controlled trials of initial efficacy need to be supplemented by evaluation strategies for long-term surveillance of community-based programs that guide implementation while assessing long-term effectiveness., (© 2021 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

Despite major expansions of evidence-based treatments of common mental disorders in recent decades, especially antidepressant medication, the point prevalence of depression has not decreased; instead it probably increased in young adults. We question whether antidepressants (AD)-monotherapy and low-fidelity-to-guideline psychological treatment (PT) might have no effect or even adverse effects in some patients and contexts that dilute the benefits of treatment at the population level, making it harder for population-based studies to detect treatment-driven prevalence reductions. Randomized Clinical Trial (RCT)s have not identified these effects because AD-monotherapy and low-fidelity PT are uncommon in RCTs where treatment protocols are specified and carefully monitored, unlike treatment in real-world settings. Second, RCTs may have missed the bigger picture of ultimate outcomes due to too short follow-ups. We elaborate two mechanisms through which AD-monotherapy and low-fidelity PT could produce adverse effects on long-term illness course. Both mechanisms are speculative and we outline how to test.

Background: Mental health problems during adolescence may create a problematic start into adulthood for affected individuals. Usually, categorical indicators of adolescent mental health issues (yes/no psychiatric disorder) are used in studies into long-term functional outcomes. This however does not take into account the full spectrum of mental health, nor does it consider the trajectory of mental health problem development over time. The aim of this study was twofold: (1) to identify distinct developmental trajectories of (co-occurring) internalizing and externalizing mental health symptoms over the course of adolescence (ages 11-19), and (2) to document the associations between these adolescent trajectories and economic, social, and health outcomes in young adulthood (age 22), unadjusted and adjusted for childhood functioning, putative confounders and current mental health., Methods: Data were used from the Dutch TRAILS cohort study (subsample n = 1524, 47.3% males). Self-reported INT and EXT symptoms using the Youth/Adult Self Report were assessed four times (ages 11y, 13y, 16y, 19y). Adolescent mental health trajectories were estimated using Parallel-Processes Latent Class Growth Analyses. Self-reported economic, social, and health outcomes and parent-reported current mental health (using Adult Behaviour Checklist) were assessed at age 22. Multiple logistic regression analyses were performed to test associations between trajectories and outcomes., Results: Four distinct trajectory classes were identified: (1) a normative class with decreasing-low INT+EXT symptoms (n = 460), (2) continuous moderately-high INT+EXT (n = 298), (3) continuous moderate, INT>EXT (n = 414), and (4) decreasing moderate, EXT>INT (n = 352). Compared to the normative class, the other three trajectories generally predicted less optimal early-adult outcomes, with the strongest effects observed for individuals with continuous moderate-high levels of both INT and EXT symptoms throughout adolescence. The associations largely remained after adjustment for pre-adolescent functioning, selected confounders and current mental health., Conclusions: Both adolescent trajectories and current mental health had substantial independent effects on early-adult functioning., Competing Interests: The authors have declared that no competing interests exist.

Background: Perinatal depression and anxiety are associated with unfavourable child outcomes., Aims: To assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive-behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242., Method: Pregnant women (n = 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT (n = 140) or CAU (n = 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother-infant bonding and child cognitive and motor development at age 18 months., Results: In total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI -1.82 to 4.57); t = 0.85, P = 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. A post hoc analysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group., Conclusions: Prenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background: The structure of psychopathology has been much debated within the research literature. This study extends previous work by providing comparisons of the links between psychopathology and several life outcomes (temperamental, economic, social, psychological and health) using a three-correlated-factors model, a bifactor model, a revised-bifactor model and a higher-order model., Methods: Data from a sample of Dutch adolescents were used (n = 2 230), and psychopathology factors were modelled using self-reported and parent-reported longitudinal data from youth across four assessments during adolescence, from ages 11 to 19. Outcome variables were assessed at age 22 using adolescent-reports and parent-reports and more objective measures (e.g. body mass index)., Results: While no measurement model was clearly superior, we found modest associations between the psychopathology factors and life outcomes. Importantly, after taking into account a general factor, the associations with life outcomes decreased for the residual parts of thought problems (across all domains) and internalizing problems (for temperamental and psychological outcomes), but not for externalizing problems, compared with the traditional three-correlated-factors model. Patterns were similar for adolescent-reported and parent-reported data., Conclusions: Findings suggest that a general factor is related to psychopathology and life outcomes in a meaningful way. Results are discussed in terms of individual differences in propensity to psychopathology and more broadly in light of recent developments concerning the structure of psychopathology. © 2019 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd., (© 2019 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.)

Background: Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents., Methods: We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents)., Results: These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected., Conclusions: These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.

Purpose of Review: Since the 70s, treatment of depression, especially pharmacologically, has expanded enormously. However, epidemiological studies show that 12-month population prevalence rates have not dropped. This observation raises multiple questions. How good are treatments of depression actually? Do they improve long-term outcomes? Have the treatment gaps narrowed? And how can we make mental healthcare more effective at the population level?, Recent Findings: Recent publications suggest some answers. Controlled treatment trials show that effectiveness of specific treatments (pharmacological, psychological) is modest and probably overestimated owing to substantial spontaneous recovery and nonspecific therapeutic effects. Treatment gaps are still substantial and prevention has unclear long-term effects and is not structurally embedded. Future relevance of genetic information for better personalized treatment is potentially high but uncertain. Increasingly, the potential of treatment to improve long-term outcome is being questioned., Summary: To reduce prevalence, it is essential to narrow the treatment gaps, provide timely interventions and high-quality treatment, eradicate waiting lists, prescribe antidepressants more cautiously and better managed, consider psychological alternatives, and provide more psychosocial treatment in primary care with physician-assistants. In addition, research is needed on long-term outcome of different treatment modalities, and least but not last the value of structurally socially embedded preventive interventions.

The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes with new challenges. Using the watershed model of genotype-phenotype relationships as a conceptual aid and recent genetic findings on other complex phenotypes, we discuss why it took so long and identify seven future challenges. The biggest challenge involves the identification of causal mechanisms since GWAS associations merely flag genomic regions without a direct link to underlying biological function. Furthermore, the genetic association with the index phenotype may also be part of a more extensive causal pathway (e.g., from variant to comorbid condition) or be due to indirect influences via intermediate traits located in the causal pathways to the final outcome. This challenge is highly relevant for depression because even its narrow definition of major depressive disorder captures a heterogeneous set of phenotypes which are often measured by even more broadly defined operational definitions consisting of a few questions (minimal phenotyping). Here, Mendelian randomization and future discovery of additional genetic variants for depression and related phenotypes will be of great help. In addition, reduction of phenotypic heterogeneity may also be worthwhile. Other challenges include detecting rare variants, determining the genetic architecture of depression, closing the "heritability gap", and realizing the potential for personalized treatment. Along the way, we identify pertinent open questions that, when addressed, will advance the field.

This study aims to test whether adolescent negative social interactions mediate the relation between early adolescent self-regulatory capacities and young adult psychopathology, using a fully prospective mediation model. Data were derived from the Tracking Adolescents' Individual Lives Survey, a large population cohort of Dutch adolescents (n = 962). At age 11, three indicators of self-regulation were assessed: low frustration, high effortful control, and high response inhibition. Negative social interactions between ages 11 and 22 were captured twice using the Event History Calendar. Psychopathology (i.e., internalizing and externalizing problems) was assessed at ages 11 and 22. Findings indicate that adolescents' frustration and effortful control but not response inhibition assessed at age 11 are related to both internalizing and externalizing problems at age 22, after controlling for psychopathology at age 11, sex, and socioeconomic status. These associations were partly (about 22%) mediated by the negative social interactions adolescents experienced. Effect sizes were all modest. This study shows that self-regulation is related to subsequent psychopathology in part through its effect on negative social interactions, providing evidence for sequences of self-regulatory capacities, life experiences, and developmental outcomes.

Background: As depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact., Method: Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model., Results: Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD., Conclusions: Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach., (© 2018 World Psychiatric Association.)

The neural substrate of cognitive reappraisal has been well-mapped. Individuals who successfully downregulate negative affect (NA) by reshaping their thoughts about a potentially emotional situation show augmented activity in the prefrontal cortex (PFC), with attenuated activity in the amygdala. We performed functional neuroimaging with experience sampling to determine whether individual differences in brain activation correspond to differences in real-life NA. While being scanned, 69 female students (aged 18-25 years) were asked to perform a cognitive reappraisal task. In addition, repeated assessments (5/day, 14 days) of affect and minor events in real-life were conducted. Individual t-maps were created for an instructed downregulation contrast (downregulate negative-attend negative) and an uninstructed regulation contrast (attend negative-attend neutral). Mean beta values were extracted from a priori defined regions of interest in the bilateral amygdala and PFC and were correlated with three daily life NA measures: baseline (mean) NA, NA variability, and NA reactivity to negative events. Only one out of twelve correlations for the amygdalae was nominally significant, which did not survive correction for multiple comparisons. PFC activation in the instructed and uninstructed regulation contrasts explained approximately 10% of the variance in NA reactivity; stronger recruitment during the attend-negative condition was correlated with lower reactivity levels. The degree to which individuals spontaneously engage frontal clusters may be a critical aspect of real-life emotional reactivity. The findings of this study provide a partial external validation of the cognitive reappraisal task, suggesting that frontal brain activation during implicit task conditions may have the strongest connection with real-life behaviors., Competing Interests: The authors have declared that no competing interests exist.

It is not clear if treatments for depression targeting repetitive negative thinking (RNT: rumination, worry and content-independent perseverative thinking) have a specific effect on RNT resulting in better outcomes than treatments that do not specifically target rumination. We conducted a systematic search of PsycINFO, PubMed, Embase and the Cochrane library for randomized trials in adolescents, adults and older adults comparing CBT treatments for (previous) depression with control groups or with other treatments and reporting outcomes on RNT. Inclusion criteria were met by 36 studies with a total of 3307 participants. At post-test we found a medium-sized effect of any treatment compared to control groups on RNT (g = 0.48; 95% CI: 0.37-0.59). Rumination-focused CBT: g = 0.76, <0.01; Cognitive Control Training: g = 0.62, p < .01; CBT: g = 0.57, p < .01; Concreteness training: g = 0.53, p < .05; and Mindfulness-based Cognitive Therapy: g = 0.42, p < .05 had medium sized and significantly larger effect sizes than other types of treatment (i.e., anti-depressant medication, light therapy, engagement counseling, life review, expressive writing, yoga) (g = 0.14) compared to control groups. Effects on RNT at post-test were strongly associated with the effects on depression severity and this association was only significant in RNT-focused CBT. Our results suggest that in particular RNT-focused CBT may have a more pronounced effect on RNT than other types of interventions. Further mediation and mechanistic studies to test the predictive value of reductions in RNT following RNT-focused CBT for subsequent depression outcomes are called for., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence., Methods: In this single-blind, multicentre, parallel, three-group, randomised controlled trial, individuals recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (10:10:8) to PCT and antidepressants, antidepressants alone, or PCT with tapering of antidepressants, using computer-generated randomised allocation stratified for number of previous depressive episodes and type of care. Eligible participants had previously experienced at least two depressive episodes and were in remission or recovery on antidepressants, which they had been receiving for at least the past 6 months. Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage. The primary outcome was time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, assessed four times in 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked. This trial is registered with the Netherlands Trial Register, number NTR1907., Findings: Between July 14, 2009, and April 30, 2015, 2486 participants were assessed for eligibility and 289 were randomly assigned to PCT and antidepressant (n=104), antidepressant alone (n=100), or PCT with tapering of antidepressant (n=85). The overall log-rank test was significant (p=0·014). Antidepressants alone were not superior to PCT while tapering off antidepressants in terms of the risk of relapse or recurrence (hazard ratio [HR] 0·86, 95% CI 0·56-1·32; p=0·502). Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction compared with antidepressants alone (0·59, 0·38-0·94; p=0·026). There were two suicide attempts (one in the antidepressants alone group and one in the PCT with tapering of antidepressants group) and one death (in the PCT and antidepressants group) not related to the interventions during the 24 months' follow-up., Interpretation: Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding PCT to antidepressant treatment after recovery is superior to antidepressants alone. PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery., Funding: The Netherlands Organisation for Health Research and Development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

From the literature it is not clear whether low resting heart rate (HR) reflects low or high sensitivity to the detrimental effects of adverse environments on externalizing problems. We studied parental psychiatric history (PH), reflecting general vulnerability, as possible moderator explaining these inconsistencies. Using Linear Mixed Models, we analyzed data from 1914 subjects, obtained in three measurement waves (mean age 11, 13.5, and 16 years) from the TRacking Adolescents' Individual Lives Survey population-based cohort and the parallel clinic-referred cohort. As hypothesized, more chronic stressors predicted more externalizing problems in vulnerable individuals with high resting HR but not in those with low resting HR, suggesting high vs. low sensitivity, respectively, to adverse environmental influences. Low sensitivity to adverse environmental influences in vulnerable individuals exposed to high stressor levels was additionally confirmed by high heart rate variability (Root Mean Squared Successive Difference; RMSSD). In adolescents with low vulnerability, in contrast, the association between chronic stressors and externalizing problems did not substantially differ by resting HR and RMSSD. Future research may demonstrate whether our findings extend to other adverse, or beneficial, influences. Notwithstanding their theoretical interest, the effects were small, only pertained to parent-reported externalizing problems, refer to a small subset of respondents in our sample, and are in need of replication. We conclude that HR and RMSSD are unlikely to be strong moderators of the association between stressors and externalizing problems., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The existing literature does not provide consistent evidence that carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to adverse environmental influences, resulting in enhanced externalizing problems, compared to noncarriers. One explanation is that the adverse influences examined in prior studies were not severe, chronic, or distressing enough to reveal individual differences in sensitivity reflected by DRD4-7R. This study examined whether the 7-repeat allele moderated the association between chronic stressors capturing multiple stressful aspects of individuals' lives and externalizing problems in adolescence. We expected that chronic stressor levels would be associated with externalizing levels only in 7-repeat carriers. Using Linear Mixed Models, we analyzed data from 1621 Dutch adolescents (52.2% boys), obtained in three measurement waves (mean age approximately 11, 13.5, and 16 years) from the TRacking Adolescents' Individual Lives Survey (TRAILS) population-based birth cohort and the parallel clinic-referred cohort. Across informants, we found that higher levels of chronic stressors were related to higher externalizing levels in 7-repeat carriers but not in noncarriers, as hypothesized. Although previous studies on the 7-repeat allele as a moderator of environmental influences on adolescents' externalizing problems have not convincingly demonstrated individual differences in sensitivity to adverse environmental influences, our findings suggest that adolescent carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to chronic, multi-context stressors than noncarriers.

Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.

Objective: Our study aims to estimate the proportion of the phenotypic variance of Neuroticism and its facet scales that can be attributed to common single-nucleotide polymorphisms (SNPs) in two adult populations from Estonia (EGCUT; N = 3,292) and the Netherlands (Lifelines; N = 13,383)., Method: Genomic-relatedness-matrix restricted maximum likelihood (GREML) using genome-wide complex trait analysis (GCTA) software was employed. To build upon previous research, we used self- and informant reports of the 30-facet NEO personality inventories and analyzed both the usual sum scores and the residual facet scores of Neuroticism., Results: In the EGCUT cohort, the proportion of phenotypic variance explained by the additive effects of common genetic variants in self- and informant-reported Neuroticism domain scores was 15.2% (p = .070, SE = .11) and 6.2% (p = .293, SE = .12), respectively. The SNP-based heritability estimates at the level of Neuroticism facet scales differed greatly across cohorts and modes of measurement but were generally higher (a) for self- than for informant reports, and (b) for sum than for residual scores., Conclusions: Our findings indicate that a large proportion of the heritability of Neuroticism is not captured by additive genetic effects of common SNPs, with some evidence for Gene × Environment interaction across cohorts., (© 2016 Wiley Periodicals, Inc.)

The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19. Adolescents who reported being exposed to social defeat showed increases in basal cortisol (ɳ 2 =0.029) and decreases in reaction to the stress task (ɳ 2 =0.030) from age 16-19, compared to their peers in the loss/illness and no stress group. The current study provides unique longitudinal data on the role of adversity in HPA-axis functioning. Evidence is provided that adversity can affect the body's neuroendocrine response to stress, dependent on the nature of both the HPA-measures and adverse events under study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mental health in China is of growing concern to both policy-makers and researchers. The Tianjin Mental Health Survey (TJMHS) was conducted between July 2011 and March 2012 to assess the prevalence and risk factors of mental disorders in the context of recent economic growth and other socio-demographic changes in Tianjin, a municipality of 13 million on China's eastern seaboard. A multistage cluster random sample selected using probability proportionate to size methods participated in a two-phase screening procedure: 11,748 subjects 18 or older were screened for risk of psychopathology and then an enriched risk-proportional subsample of 4,438 subjects was interviewed by psychiatrists using an expanded Chinese version of the Structured Clinical Interview for Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) Axis I disorders (SCID). The study also collected information about the impairment associated with mental disorders, mental health literacy, the stigmatization of mental disorders, and help-seeking behavior for psychological problems. This paper provides a detailed overview of the study rationale, objectives, field procedures, and pattern of response. It highlights several of the methodological challenges of maintaining quality control of a complex epidemiological study in the Chinese setting, issues that are relevant to other community-based epidemiological studies in low- and middle-income countries., (Copyright © 2016 John Wiley & Sons, Ltd.)

This corrects the article DOI: 10.1038/ncomms15805.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g <-0.55) and blood pressure (-0.35g <-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: This study examined whether changes in mindfulness skills following Mindfulness-based Cognitive Therapy (MBCT) are predictive of long-term changes in personality traits., Methods: Using data from the MOMENT study, we included 278 participants with recurrent depression in remission allocated to Mindfulness-Based Cognitive Therapy (MBCT). Mindfulness skills were measured with the FFMQ at baseline, after treatment and at 15-month follow-up and personality traits with the NEO-PI-R at baseline and follow-up., Results: For 138 participants, complete repeated assessments of mindfulness and personality traits were available. Following MBCT participants manifested significant improvement of mindfulness skills. Moreover, at 15-month follow-up participants showed significantly lower levels of neuroticism and higher levels of conscientiousness. Large improvements in mindfulness skills after treatment predicted the long-term changes in neuroticism but not in conscientiousness, while controlling for use of maintenance antidepressant medication, baseline depression severity and change in depression severity during follow-up (IDS-C). In particular improvements in the facets of acting with awareness predicted lower levels of neuroticism. Sensitivity analyses with multiple data imputation yielded similar results., Limitations: Uncontrolled clinical study with substantial attrition based on data of two randomized controlled trials., Conclusions: The design of the present study precludes to establish whether there is any causal association between changes in mindfulness and subsequent changes in neuroticism. MBCT could be a viable intervention to directly target one of the most important risk factors for onset and maintenance of recurrent depression and other mental disorders, i.e. neuroticism., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Childhood subthreshold manic symptoms may represent a state of developmental vulnerability to Bipolar Disorder (BD) and may also be associated with other adverse psychiatric outcomes. To test this hypothesis we examined the structure and predictive value of childhood subthreshold manic symptoms for common psychiatric disorders presenting by early adulthood., Methods: Subthreshold manic symptoms at age 11 years and lifetime clinical outcomes by age 19 years were ascertained in the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective Dutch community cohort. We used latent class analysis to identify subthreshold manic symptom profiles at baseline. The association between class membership and subsequent clinical diagnoses of BD (comprising BD-I, BD-II, mania and hypomania), depressive, anxiety and substance abuse disorders was determined using Cox proportional-hazard ratio (HR) models., Results: At age 11 years, we identified a normative (n=916; 47%), a mildly symptomatic (n=843; 43%) and a highly symptomatic class (n=198; 10%). Referenced to the normative class, the sex- and age-adjusted risk of new-onset BD by the age of 19 years was significantly increased in the mildly (HR=2.01, 95%CI 1.13-3.59) and highly symptomatic classes (HR=5.02, 95%CI 2.48-10.16). These estimates remained significant after further adjustments for cognitive and family function, parental socioeconomic status, parental psychiatric morbidity, and comorbid disorders at baseline (p-value for linear trend across classes<0.01). Class membership did not show significant associations with incident depressive, anxiety and substance abuse disorders in the fully adjusted regression models., Limitations: The period of risk for adult-onset BD extends beyond the observational period of the study., Conclusions: Elevated childhood subthreshold manic symptoms are associated with increased risk of BD by early adulthood and are therefore a potentially useful phenotype for the early identification of at-risk individuals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Personality similarity between parent and offspring has been suggested to play an important role in offspring's development of externalizing problems. Nonetheless, much remains unknown regarding the nature of this association. This study aimed to investigate the effects of parent-offspring similarity at different levels of personality traits, comparing expectations based on evolutionary and goodness-of-fit perspectives. Two waves of data from the TRAILS study ( N  = 1587, 53% girls) were used to study parent-offspring similarity at different levels of personality traits at age 16 predicting externalizing problems at age 19. Polynomial regression analyses and Response Surface Analyses were used to disentangle effects of different levels and combinations of parents and offspring personality similarity. Although several facets of the offspring's personality had an impact on offspring's externalizing problems, few similarity effects were found. Therefore, there is little support for assumptions based on either an evolutionary or a goodness-of-fit perspective. Instead, our findings point in the direction that offspring personality, and at similar levels also parent personality might impact the development of externalizing problems during late adolescence. © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology.

Alterations in physiological reactivity to stress are argued to be central mechanisms linking adverse childhood environmental experiences to internalizing and externalizing psychopathology. Childhood trauma exposure may influence physiological reactivity to stress in distinct ways from other forms of childhood adversity. This study applied a novel theoretical model to investigate the impact of childhood trauma on cardiovascular stress reactivity - the biopsychosocial model of challenge and threat. This model suggests that inefficient cardiovascular responses to stress - a threat as opposed to challenge profile - are characterized by blunted cardiac output (CO) reactivity and increased vascular resistance. We examined whether childhood trauma exposure predicted an indicator of the threat profile of cardiovascular reactivity and whether such a pattern was associated with adolescent psychopathology in a population-representative sample of 488 adolescents (M=16.17years old, 49.2% boys) in the TRacking Adolescents' Individual Lives Survey (TRAILS). Exposure to trauma was associated with both internalizing and externalizing symptoms and a pattern of cardiovascular reactivity consistent with the threat profile, including blunted CO reactivity during a social stress task. Blunted CO reactivity, in turn, was positively associated with externalizing, but not internalizing symptoms and mediated the link between trauma and externalizing psychopathology. None of these associations varied by gender. The biopsychosocial model of challenge and threat provides a novel theoretical framework for understanding disruptions in physiological reactivity to stress following childhood trauma exposure, revealing a potential pathway linking such exposure with externalizing problems in adolescents., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis., Method: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated., Results: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96., Conclusion: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants., Competing Interests: Dr. Hudziak has received grant or research support from the National Institutes of Health, the National Institute of Mental Health, the National Institute of Diabetes and Digestive and Kidney Disease, and the state of Vermont. His primary appointment is with the University of Vermont. He has additional appointments with Erasmus University in Rotterdam, Netherlands, Washington University School of Medicine in St. Louis, Missouri, and the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. Drs. Middeldorp, Groen-Blokhuis, St Pourcain, Greven, Pappa, Tiesler, Nolte, Ebejer, Zhao, Davies, Ehli, Evans, Guxens, Hottenga, Jugessur, Kemp, Martin, Myhre, Ormel, Ring, Standl, Stergiakouli, Stoltenberg, Thiering, Timpson, Trzaskowski, van der Most, Nyholt, Medland, Neale, Jacobsson, Sunyer, Hartman, Whitehouse, Pennell, Heinrich, Plomin, Smith, Tiemeier, Posthuma, Boomsma, Ms. Hammerschlag, Mr. Ouwens, Mr. Ang, Ms. Vilor-Tejedor, Mr. Bacelis, Ms. Fedko, Ms. Krapohl, Mr. Murcia, and Ms. Wang report no biomedical financial interests or potential conflicts of interest., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of the present study was to investigate whether executive functioning (EF) in early adolescence predicted alcohol use disorder (AUD) in late adolescence and whether adolescents with AUD differed in maturation of EF from controls without a diagnosis., Methods: We used the data from the Tracking Adolescents' Individual Lives Survey (TRAILS), a cohort of 2230 Dutch adolescents. Working memory, inhibition, and attention were measured at ages 11 and 19. At age 19, lifetime DSM-IV diagnoses were determined, resulting in a control group (n = 1111) and two AUD groups, i.e., alcohol abusers (n = 381) and alcohol dependents (n = 51). Regression analyses assessed whether EF at age 11 predicted the transition to AUD in late adolescence and whether AUD affected maturation of EF from age 11 to 19., Results: EF in early adolescence did not predict AUD in late adolescence. A significant interaction effect emerged between gender and alcohol dependence for shift attention (β = 0.12, SE=0.36), with girls showing smaller maturational rates. This effect remained significant after controlling for alcohol intake (ages 16 and 19) and comorbid psychiatric disorders., Discussion: Our results do not replicate the finding that EF in early adolescence is a significant predictor of AUD in late adolescence. Furthermore, for the majority of tasks, adolescents with AUD do not differ in EF maturation over the course of adolescence. Alcohol dependent girls however, show less maturation of shift attention. This is independent of the quantity of alcohol intake, which could suggest that non-normative maturation of EF is associated with the behavioural components of AUD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Although loss of pleasure (i.e., anhedonia) is one of the two core symptoms of depression, very little research has examined the relation between depressive symptoms and the experience of pleasure in daily life. This exploratory study in two population-based adolescent samples aimed to examine how depressive symptoms and anhedonia specifically were related to (1) the proportion and intensity of positive events, (2) mean and variability of positive affect (PA), (3) reactivity to positive events, and (4) reactivity to PA (i.e., whether PA elicits positive events). We used Experience Sampling to measure positive events and PA several times a day during 6 to 14 days in early (N = 284) and late (N = 74) adolescents. Results showed that depressive symptoms were related to a lower proportion and intensity of positive events, lower mean PA, and higher variability in PA regardless of sex and stage of adolescence. No clear evidence was found for differential reactivity to positive events or to PA. Anhedonia was not associated with most daily life experiences of pleasure. Our findings, though preliminary, suggest that although adolescents with many depressive symptoms experience less positive events and lower PA, they are able to enjoy pleasurable events to the same extent as individuals with fewer depressive symptoms.

The aim of the study was to estimate the proportion of adolescents with and without a psychiatric diagnosis receiving specialist mental health care and investigate their problem levels as well as utilization of other types of mental health care to detect possible over- and undertreatment. Care utilization data were linked to psychiatric diagnostic data of 2230 adolescents participating in the TRAILS cohort study, who were assessed biannually starting at age 11. Psychiatric diagnoses were established at the fourth wave by the Composite International Diagnostic Interview. Self-, parent- and teacher-reported emotional and behavioral problems and self-reported mental health care use were assessed at all four waves. Of all diagnosed adolescents, 35.3 % received specialist mental health care. This rate increased to 54.5 % when three or more disorders were diagnosed. Almost a third (28.5 %) of specialist care users had no psychiatric diagnosis; teachers gave them relatively high ratings on attention and impulsivity subscales. Diagnosed adolescents without specialist mental health care also reported low rates of other care use. We found no indication of overtreatment. Half of the adolescents with three or more disorders do not receive specialist mental health care nor any other type of care, which might indicate unmet needs.

Background: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied., Aims: To investigate whether MBCT with discontinuation of mADM is non-inferior to MBCT+mADM., Method: A multicentre randomised controlled non-inferiority trial (ClinicalTrials.gov:NCT00928980). Adults with recurrent depression in remission, using mADM for 6 months or longer (n= 249), were randomly allocated to either discontinue (n= 128) or continue (n= 121) mADM after MBCT. The primary outcome was depressive relapse/recurrence within 15 months. A confidence interval approach with a margin of 25% was used to test non-inferiority. Key secondary outcomes were time to relapse/recurrence and depression severity., Results: The difference in relapse/recurrence rates exceeded the non-inferiority margin and time to relapse/recurrence was significantly shorter after discontinuation of mADM. There were only minor differences in depression severity., Conclusions: Our findings suggest an increased risk of relapse/recurrence in patients withdrawing from mADM after MBCT., (© The Royal College of Psychiatrists 2016.)

Subject-specific and marginal models have been developed for the analysis of longitudinal ordinal data. Subject-specific models often lack a population-average interpretation of the model parameters due to the conditional formulation of random intercepts and slopes. Marginal models frequently lack an underlying distribution for ordinal data, in particular when generalized estimating equations are applied. To overcome these issues, latent variable models underneath the ordinal outcomes with a multivariate logistic distribution can be applied. In this article, we extend the work of O'Brien and Dunson (2004), who studied the multivariate t-distribution with marginal logistic distributions. We use maximum likelihood, instead of a Bayesian approach, and incorporated covariates in the correlation structure, in addition to the mean model. We compared our method with GEE and demonstrated that it performs better than GEE with respect to the fixed effect parameter estimation when the latent variables have an approximately elliptical distribution, and at least as good as GEE for other types of latent variable distributions., (© 2015, The International Biometric Society.)

Background: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. Our aim was to investigate whether the addition of MBCT to mADM is a more effective prevention strategy than mADM alone., Methods: This study is one of two multicenter randomised trials comparing the combination of MBCT and mADM to either intervention on its own. In the current trial, recurrently depressed patients in remission who had been using mADM for 6 months or longer (n=68), were randomly allocated to either MBCT+mADM (n=33) or mADM alone (n=35). Primary outcome was depressive relapse/recurrence within 15 months. Key secondary outcomes were time to relapse/recurrence and depression severity. Analyses were based on intention-to-treat., Results: There were no significant differences between the groups on any of the outcome measures., Limitations: The current study included patients who had recovered from depression with mADM and who preferred the certainty of continuing medication to the possibility of participating in MBCT. Lower expectations of mindfulness in the current trial, compared with the parallel trial, may have caused selection bias. In addition, recruitment was hampered by the increasing availability of MBCT in the Netherlands, and even about a quarter of participants included in the trial who were allocated to the control group chose to get MBCT elsewhere., Conclusions: For this selection of recurrently depressed patients in remission and using mADM for 6 months or longer, MBCT did not further reduce their risk for relapse/recurrence or their (residual) depressive symptoms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Aims: Excessive alcohol use is assumed to affect maturation of cognitive functioning in adolescence. However, most existing studies that have tested this hypothesis are seriously flawed due to the use of selective groups and/or cross-sectional designs, which limits the ability to draw firm conclusions. This longitudinal study investigated whether patterns of alcohol use predicted differences in maturation of executive functioning in adolescence. Additionally, gender was tested as a possible moderator., Methods: We used data from the Tracking Adolescents' Individual Lives Survey (TRAILS), which comprises a cohort of 2,230 Dutch adolescents. Maturation of executive functioning was measured by assessing the standardized improvement on each of four basic executive functions (i.e., inhibition, working memory, and shift- and sustained attention) between ages 11 and 19. Participants were assigned to one of six (heavy) drinking groups (i.e., non-drinkers, light drinkers, infrequent heavy drinkers, increased heavy drinkers, decreased heavy drinkers, and chronic heavy drinkers). We conducted linear regression analyses, and adjusted for relevant confounders., Results: The six drinking groups did not reveal significant differences in maturation between drinking groups. E.g., maturation executive functioning of chronic heavy drinkers in comparison to non-drinkers; inhibition: B = -0.14, 95% CI [-0.41 to 0.14], working memory: B = -0.03, 95% CI [-0.26 to 0.21], shift attention: B = 0.13, 95% CI [-0.17 to 0.41], sustained attention: B = 0.12, 95% CI [-0.60 to 0.36]. Furthermore, gender was not found to be a significant moderator., Conclusions: Four years of weekly heavy drinking (i.e., chronic heavy drinkers) did not result in measurable impairments in four basic executive functions. Thus, regular heavy drinking in adolescence does not seem to affect these basic behavioural measures of executive functioning.

Unfair treatment may evoke more negative emotions in individuals scoring higher on neuroticism, thereby possibly impacting their decision-making in these situations. To investigate the neural basis of social decision-making in these individuals, we examined interpersonal reactions to unfairness in the Ultimatum Game (UG). We measured brain activation with fMRI in 120 participants selected based on their neuroticism score, while they made decisions to accept or reject proposals that were either fair or unfair. The anterior insula and anterior cingulate cortex were more activated during the processing of unfair offers, consistent with prior UG studies. Furthermore, we found more activation in parietal and temporal regions for the two most common decisions (fair accept and unfair reject), involving areas related to perceptual decision-making. Conversely, during the decision to accept unfair offers, individuals recruited more frontal regions previously associated with decision-making and the implementation of reappraisal in the UG. High compared to low neurotic individuals did not show differential activation patterns during the proposal of unfair offers; however, they did show lower activation in the right dorsal striatum (putamen) during the acceptance of unfair offers. This brain region has been involved in the formation of stimulus-action-reward associations and motivation/arousal. In conclusion, the findings suggest that both high and low neurotic individuals recruit brain regions signaling social norm violations in response to unfair offers. However, when it comes to decision-making, it seems that neural circuitry related to reward and motivation is altered in individuals scoring higher on neuroticism, when accepting an unfair offer.