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.
High neuroticism predicts psychopathology and physical health problems. Nongenetic factors, including major life events and experiences, explain approximately half of the variance in neuroticism. ...Conversely, neuroticism also predicts these life experiences. In this study, we aimed to quantify the reciprocal causation between neuroticism and life experiences and to gauge the magnitude and persistence of these associations. This longitudinal cohort study included 5 assessment waves over 16 years in a random sample of 296 Dutch participants (47% women) with a mean age of 34 years (SD = 12, range 16-63 years). Neuroticism was assessed with the Amsterdam Biographic Questionnaire. The experiences measured included positive and negative life events, long-term difficulties (LTDs), and change in life quality, all assessed by contextual rating procedures adapted from the Life Event and Difficulties Schedule. We fit structural equation models in Mplus. Results showed that neuroticism consistently predicted negative experiences, decreased life quality, and LTDs (β = 0.15 to 0.39), whereas effects on positive experiences were variable (β = 0.14). LTDs and deteriorated life quality each predicted small but persistent increases in neuroticism (β = 0.18), whereas improved life quality predicted small but persistent decreases (β = −0.13). This suggests set point change in neuroticism. Life event aggregates showed no persistent effects on the neuroticism set point. Neuroticism and life experiences showed persistent, bidirectional associations. Experience-driven changes in neuroticism lasted over a decade. Results support the corresponsive principle (reciprocal causation), suggesting a mixed model of change in neuroticism that distinguishes temporary changes in neuroticism from persistent changes in an individual's neuroticism set point.
Neuroticism's prospective association with common mental disorders (CMDs) has fueled the assumption that neuroticism is an independent etiologically informative risk factor. This vulnerability model ...postulates that neuroticism sets in motion processes that lead to CMDs. However, four other models seek to explain the association, including the spectrum model (manifestations of the same process), common cause model (shared determinants), state and scar models (CMD episode adds temporary/permanent neuroticism). To examine their validity we reviewed literature on confounding, operational overlap, stability and change, determinants, and treatment effects. None of the models is able to account for (virtually) all findings. The state and scar model cannot explain the prospective association. The spectrum model has some relevance, especially for internalizing disorders. Common causes are most important but the vulnerability model cannot be excluded although confounding of the prospective association by baseline symptoms and psychiatric history is substantial. In fact, some of the findings, such as interactions with stress and the small decay of neuroticism's effect over time, are consistent with the vulnerability model. We describe research designs that discriminate the remaining models and plea for deconstruction of neuroticism. Neuroticism is etiologically not informative yet but useful as an efficient marker of non-specified general risk.
•Neuroticism (N) predicts common mental disorders (CMDs) but confounding is substantial.•Five models have been proposed to explain the prospective N-CMD association.•The most explanatory models are common cause, spectrum, and vulnerability model.•N is etiologically not very informative but an easy marker of non-specified general risk.•We need to establish whether interventions targeting neuroticism reduce CMD risk.
Little is known about the epidemiology of adult attention-deficit hyperactivity disorder (ADHD).
To estimate the prevalence and correlates of DSM-IV adult ADHD in the World Health Organization World ...Mental Health Survey Initiative.
An ADHD screen was administered to respondents aged 18-44 years in ten countries in the Americas, Europe and the Middle East (n=11422). Masked clinical reappraisal interviews were administered to 154 US respondents to calibrate the screen. Multiple imputation was used to estimate prevalence and correlates based on the assumption of cross-national calibration comparability.
Estimates of ADHD prevalence averaged 3.4% (range 1.2-7.3%), with lower prevalence in lower-income countries (1.9%) compared with higher-income countries (4.2%). Adult ADHD often co-occurs with other DSM-IV disorders and is associated with considerable role disability. Few cases are treated for ADHD, but in many cases treatment is given for comorbid disorders.
Adult ADHD should be considered more seriously in future epidemiological and clinical studies than is currently the case.
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.
•We examined the effects of treatment for depression on repetitive negative thinking (RNT).•Treatment had a robust medium effect on RNT compared to various control conditions.•Cognitive-behavior therapy (CBT) had a larger effect than alternative treatments.•Effects on RNT were strongly associated with those on depression.•This association was only significant in CBT treatments focusing on RNT.
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.
Functional neuroimaging studies have suggested activation of midline frontoparietal brain regions to be at the core of self-related processes. However, although some studies reported involvement of ...the insula, little attention has been paid to this region as forming part of the "self"-network.
Using functional magnetic resonance imaging (fMRI), we aimed at replicating and extending previous studies by scanning subjects whilst reflecting upon their own personal qualities as compared to those of an acquaintance. A third condition with statements about general knowledge was used to control for attention, semantic processing and decision making processes. The results showed a significant effect of task in brain activity, consistent with previous findings, by which both person conditions recruited a common set of medial prefrontal and posterior regions, yet significant differences between self and other were found in the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC). Notably, significant neural activation in the left anterior insula was observed as uniquely associated with self-reflection.
The results provide further evidence for the specific recruitment of anterior MPFC and ACC regions for self-related processing, and highlight a role for the insula in self-reflection. As the insula is closely connected with ascending internal body signals, this may indicate that the accumulation of changes in affective states that might be implied in self-processing may contribute to our sense of self.
Depressive problems and academic performance, social well-being, and social problems in adolescents are strongly associated. However, longitudinal and bidirectional relations between the two remain ...unclear, as well as the role of gender. Consequently, this study focuses on the relation between depressive problems and three types of functioning in adolescents while testing gender differences. Depressive problems and functioning of 2,230 children were measured with structured questionnaires. The measurements took place biennially over 3 waves, from late childhood into adolescence (age range = 10-18 years). To examine the longitudinal relation between depression and functioning, path analyses with cross-lagged effects were conducted with structural equation modeling. Multigroup analyses were used to test for gender differences, which were only observed for academic performance. Other findings indicated substantial stability in depressive problems and functioning over time and within-wave correlations between depression and the 3 types of functioning. Poor social well-being was predicted by depressive problems but not the other way around. The relation between depressive and social problems was bidirectional, that is, they predicted each other. Finally, depressive problems and academic performance were bidirectionally related as well but only in girls.
Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders.
To ...examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries.
Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI).
Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries.
Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.
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