Elizabeth Rapa

Effects of perinatal mental disorders on the fetus and child

Perinatal mental disorders are associated with increased risk of psychological and developmental disturbances in children. However, these disturbances are not inevitable. In this Series paper, we summarise evidence for associations between parental disorders and offspring outcomes from fetal development to adolescence in high-income, middle-income, and low-income countries. We assess evidence for mechanisms underlying transmission of disturbance, the role of mediating variables (underlying links between parent psychopathology and offspring outcomes) and possible moderators (which change the strength of any association), and focus on factors that are potentially modifiable, including parenting quality, social (including partner) and material support, and duration of the parental disorder. We review research of interventions, which are mostly about maternal depression, and emphasise the need to both treat the parents disorder and help with associated caregiving difficulties. We conclude with policy implications and underline the need for early identification of those parents at high risk and for more early interventions and prevention research, especially in socioeconomically disadvantaged populations and low-income countries.

Predicting long-term outcomes for children affected by HIV and AIDS: perspectives from the scientific study of children's development

The immediate and short-term consequences of adult HIV for affected children are well documented. Little research has examined the long-term implications of childhood adversity stemming from caregiver HIV infection. Through overviews provided by experts in the field, together with an iterative process of consultation and refinement, we have extracted insights from the broader field of child development of relevance to predicting the long-term consequences to children affected by HIV and AIDS. We focus on what is known about the impact of adversities similar to those experienced by HIV-affected children, and for which there is longitudinal evidence. Cautioning that findings are not directly transferable across children or contexts, we examine findings from the study of parental death, divorce, poor parental mental health, institutionalization, undernutrition, and exposure to violence. Regardless of the type of adversity, the majority of children manifest resilience and do not experience any long-term negative consequences. However, a significant minority do and these children experience not one, but multiple problems, which frequently endure over time in the absence of support and opportunities for recovery. As a result, they are highly likely to suffer numerous and enduring impacts. These insights suggest a new strategic approach to interventions for children affected by HIV and AIDS, one that effectively combines a universal lattice of protection with intensive intervention targeted to selected children and families.

A focus on adolescence to reduce neurological, mental health and substance-use disability

Globally, there is a crucial need to prioritize research directed at reducing neurological, mental health and substance-use disorders in adolescence, which is a pivotal age for the development of self-control and regulation. In adolescence, behaviour optimally advances towards adaptive long-term goals and suppresses conflicting maladaptive short-lived urges to balance impulsivity, exploration and defiance, while establishing effective societal participation. When self-control fails to develop, violence, injury and neurological, mental health and substance-use disorders can result, further challenging the development of self-regulation and impeding the transition to a productive adulthood. Adolescent outcomes, positive and negative, arise from both a life-course perspective and within a socioecological framework. Little is known about the emergence of self-control and regulation in adolescents in low- and middle-income countries where enormous environmental threats are more common (for example, poverty, war, local conflicts, sex trafficking and slavery, early marriage and/or pregnancy, and the absence of adequate access to education) than in high-income countries and can threaten optimal neurodevelopment. Research must develop or adapt appropriate assessments of adolescent ability and disability, social inclusion and exclusion, normative development, and neurological, mental health and substance-use disorders. Socioecological challenges in low- and middle-income countries require innovative strategies to prevent mental health, neurological and substance-use disorders and develop effective interventions for adolescents at risk, especially those already living with these disorders and the consequent disability.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

POSTPARTUM GAD IS A RISK FACTOR FOR POSTPARTUM MDD: THE COURSE AND LONGITUDINAL RELATIONSHIPS OF POSTPARTUM GAD AND MDD

The objective was to examine the course and longitudinal associations of generalized anxiety disorder (GAD) and major depressive disorder (MDD) in mothers over the postpartum 2 years.

Nanoparticle augmented radiation treatment decreases cancer cell proliferation

UNLABELLED We report significant and controlled cell death using novel x-ray-activatable titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of such materials into tumor tissue can enhance the effect of radiation therapy. Herein, the incorporation of gadolinium into the NPs is designed to optimize localized energy absorption from a conventional medical x-ray. This result is further optimized by the addition of other rare earth elements. Upon irradiation, energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species (ROS). FROM THE CLINICAL EDITOR The authors report significant and controlled cell death using x-ray-activated titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species.

Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse

Background Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth. Method We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males. Results To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta. Conclusions These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition.

Mitigating the effect of persistent postnatal depression on child outcomes through an intervention to treat depression and improve parenting: a randomised controlled trial

BACKGROUND Maternal postnatal depression occurs following 10-15% of births and is associated with a range of negative child outcomes. Risks to children are particularly increased when postnatal depression is persistent. We aimed to examine whether a parenting video-feedback therapy (VFT) intervention versus a control treatment of progressive muscle relaxation (PMR), both added to cognitive behavioural therapy (CBT) for persistent postnatal depression, would lead to improved child outcomes at age 2 years. METHODS In this two-arm, parallel-design, individually randomised controlled trial, we recruited a community sample of women aged 18 years or older living within 50 miles of Oxford, UK, between 4·5 and 9·0 months post partum. All participants met diagnostic criteria for current major depressive disorder that had persisted for at least 3 months and had infants at 35 or more weeks of gestation, with a birthweight of 2000 g or greater, and without serious neonatal complications. Through a centralised service, women were randomly assigned by use of a minimisation algorithm, to receive either VFT or PMR, balanced for child sex, temperament, age, socioeconomic status, and severity of depression. Both groups also received CBT for depression. Primary outcomes were child cognitive development, language development, behaviour problems, and attachment security at age 2 years. There were 11 home-based treatment sessions before child age 1 year, followed by two booster sessions in the second year. Assessors were masked to treatment group allocation. All analyses were done according to the intention-to-treat principle. This trial is registered with the ISRCTN registry, number ISRCTN07336477. FINDINGS Between March 18, 2011, and Dec 9, 2013, we randomly assigned 144 women, 72 to each group. Primary outcome data were available for 62-64 (86-89%) VFT and 67-68 (93-94%) PMR participants. There were no group differences in child outcome (cognitive development, adjusted difference -1·01 [95% CI -5·11 to 3·09], p=0·63; language development, 1·33 [-4·16 to 6·82], p=0·63; behaviour problems, -1·77 [-4·39 to 0·85], p=0·19; attachment security, 0·02 [-0·06 to 0·10], p=0·58), with both groups achieving scores similar to non-clinical norms on all outcomes. There were six serious adverse events: five in the VFT group (in two participants) and one in the PMR group. None was treatment-related. INTERPRETATION The effect of persistent postnatal depression on children is a major public health issue. For both treatment groups there was sustained remission from depression, and child development outcomes were in the normal range. The precise mechanisms accounting for the observed positive child outcomes cannot be ascertained from this study. FUNDING Wellcome Trust.