The global burden of Common Mental Disorders (CMDs), including depressive, anxiety and substance use disorders, is substantial. Since increased treatment has not reduced CMD prevalence, prevention is a logical approach to reduce CMD burden. However, CMD prevention as currently delivered has not reduced prevalence. Seven conditions need to be met to maximize the long-term effectiveness of CMD prevention: 1. Target young persons early in life and families. 2. Modify major CMD risk and protective factors. 3. Embed in social institutions and culture. 4. Implement via synergistic programs of proven effectiveness in multiple community settings (pre-school and kindergarten, elementary and secondary schools, child and health care, social welfare/family support). 5. Secure long-term funding with permanent, structural integration into community organizations. 6. Address socio-economic disadvantage and attendant risk factors. 7. Use the power of policy. We consider how these conditions might be achieved in large populations. A dilemma is that compelling evidence regarding the benefits of CMD prevention may be needed to motivate large, long-term investments, but until society has made and sustained these investments for 10 to 20 years, full benefits of CMD prevention may not be realized. Therefore, we propose regional implementation and evaluation focused initially on proximal benefits for child development. Developmental determinants important to educators, parents and other stakeholders should be evaluated initially to establish short-term pay-offs for educational and behavioral outcomes. Long-term CMD prevention initiatives may not only prevent CMDs, but also develop resourceful, resilient, and well-educated children and adults.

Sum scores from questionnaire data are frequently analyzed under the normality assumption which is not always tenable due to for instance the skewness of the distribution, or the discreteness of the sum scores for small number of items. Alternatively, an ordinal regression analysis can be applied, but this approach seems appropriate only for very small number of items. The current state-of-the-art approach is to apply a beta-binomial model, though the beta-binomial model does not simply connect to item-response theory models that may describe the underlying items of the questionnaire, and it is more cumbersome to fit to multi domain sum scores or repeated longitudinal single sum scores. This paper proposes a normal-probit-binomial model for repeated sum scores that has an item level interpretation under certain assumptions without having to analyze the individual items. All parameters, the temporal correlation coefficients, and the mean difficulty parameter were almost unbiasedly estimated, irrespective of the set of item difficulty parameters. The coverage probability of the 95% confidence intervals were close to the nominal level, except for the correlation coefficients that were slightly liberal. Our model performed slightly better than the beta-binomial model on cross-sectional data and it handles missing items easily.

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.

Samenvatting De last van mentale problemen is enorm. Omdat zowel behandeling als preventie er tot nu toe niet in geslaagd is hun prevalentie te reduceren, benadrukken recente beleidstukken het belang van mentale gezondheid en gezonde omgevingen, en de noodzaak van een andere, bredere en integrale preventieaanpak. In dit artikel schets ik de randvoorwaarden voor zo’n effectieve preventieaanpak, waarbij ik vooral inga op voorwaarden die nog onvoldoende duidelijk zijn, zoals financiering, regie, complexiteit, het investeringsdilemma, de lange termijn, structureel gefinancierde verankering in relevante instituties, zoals zwangerschapszorg, gezinsondersteuning, onderwijs, zorg en sociale zekerheid. De vereiste investeringen zijn enorm, maar de opbrengsten zijn veelzijdig en omvangrijk.

BackgroundPsychopathology 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. MethodsIn 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. ResultsThere 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. ConclusionsLongitudinal 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.

BACKGROUND:Treatments for depression have improved, and their availability has markedly increased since the 1980s. Mysteriously, the prevalence of depression in the general population has not decreased. This &lsquo;treatment-prevalence paradox&rsquo; (TPP) raises fundamental questions about the diagnosis and treatment of depression.AIM:To clarify the TPP.METHOD:We discuss seven explanations for the TPP, based on an integrative narrative review.RESULTS:The first two explanations assume that improved and more widely available treatments did reduce the prevalence, but that the reduction has been offset by an increase in: 1. misdiagnosing distress as depression, yielding more &lsquo;false positive&rsquo; diagnoses; or 2. an actual increase in the incidence of first episodes. The remaining five explanations assume prevalence did not decrease, but suggest that 3. acute phase treatments and 4. relapse prevention are less efficacious than believed; 5. trial efficacy doesn&rsquo;t generalize to real-world settings; 6. expansion of treatment was not optimally targeted at recurrent-chronic cases which account for most prevalence; and 7. treatments have sometimes counterproductive effects.CONCLUSION:Our analysis suggest that there is little evidence that false positives or first incidence have increased as a result of error or fact but rather strong evidence that (a) the published literature overestimates treatment efficacy, that (b) treatments are considerably less effective as deployed in &lsquo;real world&rsquo; settings, and (c) that treatment impact differs substantially for chronic-recurrent cases relative to non-recurrent cases. Collectively, these three explanations probably account for most of the paradox. Further exploration of counterproductive effects of treatment is critical. Significant prevalence reduction requires not only better treatment but foremost long-term structurally funded prevention targeting powerful determinants.

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.

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.

Mood and anxiety disorders are not only common and responsible for much functional disability [1], but epidemiological studies also indicate that their prevalence, circa 10% in Western countries, has not fallen since the 1970s despite the development of evidence-based treatments [2–8]. Prevalence refers to the percentage of adults in the general population that meet diagnostic criteria in a defined period, usually the 30 days (point prevalence) or 12 months (12-month prevalence) preceding the examination irrespective of possible earlier episodes. In sharp contrast, multiple studies have documented substantial increases in expenditures on mental health care and in treatment rates in Western countries [9–15]. The evidence on increased treatment rates comes from both general practice [16–18], nation-wide morbidity registrations [19, 20], and repeated population-based surveys [8, 21]. The treatment rate increase was bolstered by the introduction of a new class of drugs in the 1980s, the selective serotonin reuptake inhibitors, aggressively marketed by Big Pharma [22]. In addition, a number of evidence-based psychological treatments became available for people with mood and anxiety disorders. The trend data on prevalence and treatment rate reveal a remarkable paradox: more treatment but not less disorders, the treatment-prevalence paradox. The expectation to see a declining trend in the prevalence of mood and anxiety disorders with an increasing trend in treatment is not unfounded. Treatment seeks to shorten illness episodes, prevent worsening and the development of comorbidity, reduce relapses and curtail recurrences. If effective, increased treatment rates should result in lower prevalence rates in the general population, but this prevalence reduction has not occurred. The increase in the use of statins has led to significant reduction in population cholesterol levels [23]. Likewise, more and better treatment of hypertension has led to less hypertension and associated illness such as heart attacks and strokes illness [24, 25]. At least seven hypotheses can explain why more and better treatments have not reduced common mental disorder prevalence: 1. Increased willingness of individuals to report symptoms and pressures to diagnose distress as anxiety or depression has inflated prevalence rates and masked a true treatment-driven prevalence drop (further: diagnostic inflation).

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.

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.

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.

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.

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.

BackgroundPerinatal depression and anxiety are associated with unfavourable child outcomes.AimsTo 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.MethodPregnant 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.ResultsIn 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. Apost hocanalysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group.ConclusionsPrenatally 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.

Background Antidepressant medications (ADMs) are widely used and long-term use is increasing. Given this extensive use and recommendation of ADMs in guidelines, one would expect ADMs to be universally considered effective. Surprisingly, that is not the case; fierce debate on their benefits and harms continues. This editorial seeks to understand why the controversy continues and how consensus can be achieved. Methods 'Position' paper. Critical analysis and synthesis of relevant literature. Results Advocates point at ADMs impressive effect size (number needed to treat, NNT = 6-8) in acute phase treatment and continuation/maintenance ADM treatment prevention relapse/recurrence in acute phase ADM responders (NNT = 3-4). Critics point at the limited clinically significant surplus value of ADMs relative to placebo and argue that effectiveness is overstated. We identified multiple factors that fuel the controversy: certainty of evidence is low to moderate; modest efficacy on top of strong placebo effects allows critics to focus on small net efficacy and advocates on large gross efficacy; ADM withdrawal symptoms masquerade as relapse/recurrence; lack of association between ADM treatment and long-term outcome in observational databases. Similar problems affect psychological treatments as well, but less so. We recommend four approaches to resolve the controversy: (1) placebo-controlled trials with relevant long-term outcome assessments, (2) inventive analyses of observational databases, (3) patient cohort studies including effect moderators to improve personalized treatment, and (4) psychological treatments as universal first-line treatment step. Conclusions Given the public health significance of depression and increased long-term ADM usage, new approaches are needed to resolve the controversy.

BACKGROUND: From around 1980, antidepressants (ad) have increasingly been prescribed, for longer periods of time, especially selective serotonin reuptake inhibitors (ssris). Paradoxically, their effectiveness is still doubted, especially outside the psychiatric profession. AIM: To explain increase and offer a perspective on causes and solutions, and to indicate how to reach consensus. METHOD: Position paper with critical analysis and synthesis of relevant literature. RESULTS: The rise in AD prescriptions results from: 1. increased safety and ease of prescribing, 2. increased presentation and recognition of depression in primary care, 3. extension of indication criteria, 4. effective marketing strategies, and 5. effectiveness in acute phase (aad) and of relapse/recurrence prevention in continuation/maintenance phases (coad).Critics point to: 1. low added value of aad relative to placebo, 2. many drop-outs and non-responders, 3. relapse/recurrence prevention with coad works only for responders to aad, 4. relapse/recurrence after AD discontinuation often involves withdrawal symptoms, and 5. publication bias, selective reporting, selective patient selection, and suboptimal blinding, resulting in overestimated effectiveness and underestimated disadvantages.Factors that keep fueling the controversy are: 1. critics stress the net effectiveness of AD whereas proponents point at gross effectiveness which includes spontaneous recovery and placebo effect; 2. persistence of distrust in industry-funded rcts; 3. ideological positions, reinforced by conflicts of interest and selective citations; 4. lack of rcts with relevant long-term outcome measurements. CONCLUSION: Although consensus is difficult to achieve given the ideological component, there are options. Three factors are critically important: confer to establish which data convince the opposition, response prediction (what works for whom), and rcts with long-term functional outcomes.

The experience of a mental disorder may affect the development of personality in multiple ways, but empirical evidence regarding psychopathology effects on personality development that persist after remission of the disorder is limited and inconsistent. In the longitudinal cohort TRacking Adolescents’ Individual Lives Survey (TRAILS), mental disorders during adolescence were assessed using the Composite International Diagnostic Interview and parent-reported effortful control, fearfulness, and frustration at age 11 and age 19 through the Early Adolescent Temperament Questionnaire. We found that adolescent mental disorders had small effects on personality change. Internalizing disorders predicted increases of fearfulness and frustration but hardly affected effortful control; externalizing disorders were unrelated to frustration and fearfulness but predicted a decrease of effortful control. Whereas fearfulness and frustration partially caught up after disorder remission, virtually all delay in effortful control was still present 2.9 years later, suggesting scarring effects.