In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others<sup>1</sup>, ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.
Obsessive-compulsive disorder (OCD) is a phenotypically heterogeneous condition characterised by time-consuming intrusive thoughts and/or compulsions. Irrespective of the symptom type diagnosed, the severity of OCD is characterised by heterogeneity in symptom presentation that complicates diagnosis and treatment. Heterogeneity of symptoms would be invaluable in an animal model. Nest building behaviour forms part of the normal behavioural repertoire of rodents and demonstrates profound between-species differences. However, it has been proposed that within-species differences in nest building behaviour (i.e. aberrant vs. normal nest building) may resemble obsessive-compulsive-like symptoms. In an attempt to investigate whether other obsessive-compulsive-like behaviours are present in an animal model of OCD, or if aberrant nest building behaviour may represent a unique obsessive-compulsive phenotype in such a model, the current study assessed nest building behaviour in high (H, viz obsessive-compulsive) and non (N, viz normal) stereotypical deer mice. Subsequently, 12 N and H animals, respectively, were provided with an excess of cotton wool daily for one week prior to and following four weeks of high-dose oral escitalopram treatment (50 mg/kg/day). Data from the current investigation demonstrate daily nesting activity to be highly variable in deer mice, with stereotypy and nest building being independent behaviours. However, we identified unique aberrant large nest building behaviour in 30% of animals from both cohorts that was attenuated by escitalopram to pre-treatment nesting scores of the larger group. In summary, behavioural and drug-treatment evidence confirms that deer mouse behaviour does indeed resemble symptom heterogeneity related to OCD, and as such expands its face and predictive validity for the disorder.
Objective: Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. Method: A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. Results: Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). Conclusions: These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction. Reprinted with permission from the American Journal of Psychiatry 2014; 171:340–349
Cognitive behavioral treatment (CBT) is the recommended intervention in bulimia nervosa (BN) and eating disorders not otherwise specified with binge/purge (EDNOS-B/P) symptoms. There are fewer data on its application in a group format. We sought to investigate the effect of group CBT in female soldiers with B/P symptomatology in an open trial design. For this purpose we assessed 64 female soldiers serving in the Israeli Defense Force diagnosed with BN and EDNOS-B/P who participated in a group CBT format of 16 weekly sessions and one follow-up session. In this study, 42 participants (65.6%) completed treatment and 22 participants (34.4%) did not. A total of 39 treatment completers (92.8% of treatment completers) and 19 non-completers (86.4% of treatment non-completers) were assessed around 12 months after treatment. Participants completed at baseline and following treatment questionnaires assessing eating-related symptoms, depression, anxiety, and overall functioning. At follow-up they were assessed for eating-related symptoms. Our findings show only minimal baseline differences between treatment completers and non-completers. Significant improvement from baseline to post-treatment was shown for B/P and restrictive symptoms, depression, anxiety, and overall functioning. At that time, more than a third of treatment completers were abstinent from binging and more than a half from vomiting. The improvement in B/P and restricting symptoms was maintained at 1 year follow-up for treatment completers. At that time around 60% were abstinent from binging and more than 70% from vomiting. Participants not completing treatment were also improved at follow-up but to a lesser extent. The findings of the present study suggest that group CBT may be effective for the treatment of female soldiers with BN and EDNOS-B/P.
Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.
Read moreAbstract Background Variation in birth registration criteria may compromise international comparisons of fetal and infant mortality. We examined the effect of birth registration practices on fetal and infant mortality rates to determine whether observed differences in perinatal and infant mortality rates were artifacts of birth registration or reflected true differences in health status. Methods A retrospective population-based cohort study was done using data from Canada, United States, Denmark, Finland, Iceland, Norway, and Sweden from 1995–2005. Main outcome measures included live births by gestational age and birth weight; gestational age—and birth weight-specific stillbirth rates; neonatal, post-neonatal, and cause-specific infant mortality. Results Proportion of live births <22 weeks varied substantially: Sweden (not reported), Iceland (0.00 %), Finland (0.001 %), Denmark (0.01 %), Norway (0.02 %), Canada (0.07 %) and United States (0.08 %). At 22–23 weeks, neonatal mortality rates were highest in Canada (892.2 per 1000 live births), Denmark (879.3) and Iceland (1000.0), moderately high in the United States (724.1), Finland (794.3) and Norway (739.0) and low in Sweden (561.2). Stillbirth:live birth ratios at 22–23 weeks were significantly lower in the United States (79.2 stillbirths per 100 live births) and Finland (90.8) than in Canada (112.1), Iceland (176.2) and Norway (173.9). Crude neonatal mortality rates were 83 % higher in Canada and 96 % higher in the United States than Finland. Neonatal mortality rates among live births ≥28 weeks were lower in Canada and United States compared with Finland. Post-neonatal mortality rates were higher in Canada and United States than in Nordic countries. Conclusions Live birth frequencies and stillbirth and neonatal mortality patterns at the borderline of viability are likely due to differences in birth registration practices, although true differences in maternal, fetal and infant health cannot be ruled out. This study emphasises the need for further standardisations, in order to enhance the relevance of international comparisons of infant mortality.
Read moreThe results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.
Read moreGreater obsessive-compulsive (OC) symptom severity may be associated with poor social adjustment. Rather than possessing deficits in social skill per se, OCD patients may be more socially isolative in the presence of normal controls. We aimed to apply a novel social interaction challenge (SIC) to an established animal model of OCD, viz., the deer mouse, to assess complex social behavior in animals by investigating group sociability and its response to chronic escitalopram treatment (50 mg/kg/day × 28 days), both within and between non (N)- (viz., normal) and high (H)- (viz., OCD-like) stereotypical cohorts. Using automated screening, we scored approach behavior, episodes of proximity, duration of proximity, and relative net weighted movement. H animals socialized more with one another within cohort in all of the above parameters compared to the within-cohort behavior of N animals. Furthermore, the social behavior of H animals toward one another, both within and between cohort demonstrated significant improvements following chronic escitalopram treatment. However, the study also demonstrates that the social interaction between H and N animals remain poor even after chronic escitalopram treatment. To conclude, findings from the current investigation support clinical data demonstrating altered sociability in patients with OCD.
Read moreFolate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.
Read moreConservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.
Read moreThis finding may represent a form of inducible urticaria, exacerbated in low-weight patients by the occurrence of binge/purge behaviors. We wish to report this observation in an attempt to widen the scope of the physical signs that may accompany eating disorders and bring this specific phenomenon into awareness. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:822-825).
Read moreAbstract Obsessive-compulsive disorder (OCD) and Obsessive-compulsive-related disorders (OCRDs) are anxiety disorders characterized by obsessions and compulsions, and varying degrees of anxiety and depression. OCRDs are considered to be one of the most disabling of psychiatric disorders and they present a tremendous economic and social burden, both for the affected individual, their family, and for society at large. In contrast to other psychiatric conditions of a comparable or lesser prevalence and patient burden, relatively little is understood about the aetiology, and cognitive effects of OCRDs. This resource includes individual chapters on the phenomenology, pathogenesis, pharmacotherapy and psychotherapy of OCD and other related disorders, and features fully updated content and research, as well as a helpful resources chapter, and an Appendix with summaries of the major rating scales used to assess patients with OCD, which will be of use to both clinicians and patients.
Read moreRecent community studies show that trauma exposure is higher in lower-income countries compared with high-income countries. PTSD prevalence rates are largely similar across countries, however, with the highest rates being found in postconflict settings. Trauma and PTSD-risk factors are distributed differently in lower-income countries compared with high-income countries, with sociodemographic factors contributing more to this risk in high-income than low-income countries. Apart from PTSD, trauma exposure is also associated with several chronic physical conditions. These findings indicate a high burden of trauma exposure in low-income countries and postconflict settings, where access to trained mental health professionals is typically low.
Read moreThe global burden of disorders has shifted from infectious disease to non-communicable diseases, including neuropsychiatric disorders. Whereas infectious disease can sometimes be combated by targeting single causal mechanisms, such as prevention of contact-spread illness by handwashing, in the case of mental disorders multiple causal mechanisms are typically relevant. The emergent field of global mental health has emphasized the magnitude of the treatment gap, particularly in the low- and middle-income world and has paid particular attention to upstream causal factors, for example, poverty, inequality, and gender discrimination in the pathogenesis of mental disorders. However, this field has also been criticized for relying erroneously on Western paradigms of mental illness, which may not be relevant or appropriate to the low- and middle-income context. Here, it is important to steer a path between scientism and skepticism. Scientism regards mental disorders as essential categories, and takes a covering law approach to causality; skepticism regards mental disorders as merely social constructions and emphasizes the role of political power in causal relations. We propose an integrative model that emphasizes the contribution of a broad range of causal mechanisms operating at biological and societal levels to mental disorders and the consequent importance of broad spectrum and multipronged approaches to intervention.
Read moreIs there a vulnerability paradox in PTSD? Pitfalls in cross-national comparisons of epidemiological data Du ckers et al 1 analyse the relationship between prevalence estimates of trauma exposure and post-traumatic stress disorder (PTSD) in published data-sets from 24 countries, and between PTSD and vulnerability (based on a country vulnerability index developed in the 2013 World Risk report). The findings are substantially counterintuitive; countries with low vulnerability have higher lifetime rates of PTSD, meaning that countries with low vulnerability and high trauma exposure have the highest rates of lifetime PTSD. The authors do emphasise a number of limitations of their work, and yet they conclude that a 'vulnerability paradox' exists for both PTSD and depression, with rates higher in countries with more resources and better healthcare systems.
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