Effect of early adversity and childhood internalizing symptoms on brain structure in young men

- Importance: Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. - Objective: To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. - Design, Setting, and Participants: A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child’s life (including prenatal exposure) and the child’s internalizing symptoms between age 7 and 13 years. - Exposures: Early childhood adversity. - Main Outcomes and Measures: The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. - Results: Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = −.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = −.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = −.08; 95% CI, −0.14 to −0.01; P = .02). - Conclusions and Relevance: Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression

Epigenetic profiling of social communication trajectories and co-occurring mental health problems: A prospective, methylome-wide association study

While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: nbirth = 804, nage 7 = 877) and trajectories of social communication deficits at age 8-17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.048) differentiated children following high (n = 80) versus low (n = 724) trajectories of social communication deficits. This differential DNAm was specific to the neonatal period and not observed at 7 years of age. Associations between DNAm and trajectory membership remained robust after controlling for co-occurring mental health problems (i.e., hyperactivity/inattention, conduct problems). The three loci identified at birth were not replicated in the Generation R Study. However, to the best of our knowledge, ALSPAC is the only study to date that is prospective enough to examine DNAm in relation to longitudinal trajectories of social communication deficits from childhood to adolescence. Although the present findings might point to potentially novel sites that differentiate between a high versus low trajectory of social communication deficits, the results should be considered tentative until further replicated

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

Background: Conduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to 'unhealthy diet'. Early-life diet also associates with DNA methylation of the insulin-like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high-fat and -sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP youth. Methods: Participants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high-fat and -sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7-13) differed for EOP versus low CP youth. Results: Prenatal 'unhealthy diet' was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal 'unhealthy diet' was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. Conclusions: Preventing 'unhealthy diet' in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation

Dimensionality of Early Adversity and Associated Behavioral and Emotional Symptoms: Data from a Sample of Japanese Institutionalized Children and Adolescents

Recent approaches have begun to identify common variance across co-occurring childhood adversities (CAs) and their associations with symptoms of psychopathology. However, few studies have investigated these questions in high-risk samples, and in different cultural contexts. This study examined common variance amongst 18 types of CAs and associated symptomatology in 457 children and adolescents living in 24 residential homes in Japan. Principal component analysis identified four significant compo

Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems

BackgroundConduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to ‘unhealthy diet’. Early‐life diet also associates with DNA methylation of the insulin‐like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high‐fat and ‐sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early‐onset persistent (EOP) versus low CP youth. MethodsParticipants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high‐fat and ‐sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7–13) differed for EOP versus low CP youth. ResultsPrenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. ConclusionsPreventing ‘unhealthy diet’ in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation. Development Psychopathology in context: famil

Exposure to Bullying and General Psychopathology: A Prospective, Longitudinal Study

Although there is mounting evidence that the experience of being bullied associates with both internalizing and externalizing symptoms, it is not known yet whether the identified associations are specific to these symptoms, or shared between them. The primary focus of this study is to assess the prospective associations

Profiling social, emotional and behavioural difficulties of children involved in direct and indirect bullying behaviours

Being involved in bullying places a child at risk of poor psychosocial and educational outcomes. This study aimed to examine the profile of behavioural, emotional and social functioning for two subtypes of bullying; direct and indirect (relational). Pupils aged between seven and eleven years old completed sociometric measures of social inclusion and bullying behaviour to identify 192 pupils considered to be involved in either direct, indirect, both or neither types of bullying. These pupils and their teachers completed a battery of assessments relating to behaviour, social competence and self-perception. All bully-groups experienced similar levels of significant social rejection. ‘Direct’ and ‘both’ groups showed the greatest number of behavioural, emotional and social difficulties, while the ‘indirect’ group showed weaknesses in self-perception, but no teacher-rated problems. Understanding the behavioural, emotional and social correlates of bullying is of particular importance for early identification of children at risk of becoming bullies and for developing targeted interventions

Research and theory for nursing and midwifery: Rethinking the nature of evidence

Background and Rationale: The rise in the principles of evidence-based medicine in the 1990s heralded a re-emerging orthodoxy in research methodologies. The view of the randomised controlled trial (RCT) as a “gold standard” for evaluation of medical interventions has extended recently to evaluation of organisational forms and reforms and of change in complex systems—within health care and in other human services. Relatively little attention has been given to the epistemological assumptions underlying such a hierarchy of research evidence. Aims and Methods: Case studies from research in maternity care are used in this article to describe problems and limitations encountered in using RCTs to evaluate some recent policy-driven and consumer-oriented developments. These are discussed in relation to theory of knowledge and the epistemological assumptions, or paradigms, underpinning health services research. The aim in this discussion is not to advocate, or to reject, particular approaches to research but to advocate a more open and critical engagement with questions about the nature of evidence. Findings and Discussion: Experimental approaches are of considerable value in investigating deterministic and probabilistic cause and effect relationships, and in testing often well-established but unevaluated technologies. However, little attention has been paid to contextual and cultural factors in the effects of interventions, in the culturally constructed nature of research questions themselves, or of the data on which much research is based. More complex, and less linear, approaches to methodology are needed to address these issues. A simple hierarchical approach does not represent the complexity of evidence well and should move toward a more cyclical view of knowledge development

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure