Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene

Background: Neuroticism is a personality trait reflecting the tendency to experience negative affect. It is a major risk for psychopathology, especially depression and anxiety disorders. Childhood maltreatment is another major risk factor for psychopathology and may influence personality. Maltreatment may interact with genotype to predict developmental outcomes. Variation in three polymorphisms of the CRHR1 gene has been found to moderate the association of childhood maltreatment with depression, and we hypothesized that it would also be linked to neuroticism. Methods: Variation in three CRHR1 SNPs (rs110402, rs242924, rs7209436) was assessed in 339 maltreated and 275 demographically similar nonmaltreated children, who participated in a day camp research program. Maltreated children were further categorized based on the number of types of maltreatment they had experienced and the most severe form of maltreatment experienced. Genotype and maltreatment status were used to predict the Big Five personality traits, as assessed by camp counselors following a week of interaction with children. Results: CRHR1 genotype significantly moderated the association of maltreatment with neuroticism but none of the other traits. Having two copies of the TAT haplotype of CRHR1 was associated with higher levels of neuroticism among maltreated children relative to nonmaltreated children, with the exception of sexually abused children and children who had experienced 3 or 4 types of abuse. Effects sizes of these interactions ranged from η² = .01 (p = .02) to η² = .03 (p = .006). Conclusions: Variation in CRHR1 moderates the association of maltreatment with neuroticism. The effects of specific types of maltreatment on neuroticism are differentially moderated by CRHR1 genotype, as are the effects of experiencing more or fewer types of maltreatment.     

Research Review: The neurobiology and genetics of maltreatment and adversity

The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual’s genetic make‐up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child’s psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic‐pituitary‐adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adulthood. We then review the neuroimaging findings of structural and functional brain differences in children and adults who have experienced childhood maltreatment. These studies offer evidence of several structural differences associated with early stress, most notably in the corpus callosum in children and the hippocampus in adults; functional studies have reported atypical activation of several brain regions, including decreased activity of the prefrontal cortex. Next we consider studies that suggest that the effect of environmental adversity may be conditional on an individual’s genotype. We also briefly consider the possible role that epigenetic mechanisms might play in mediating the impact of early adversity. Finally we consider several ways in which the neurobiological and genetic research may be relevant to clinical practice and intervention.     

Annual Research Review: Umbrella synthesis of meta-analyses on child maltreatment antecedents and interventions: differential susceptibility perspective on risk and resilience

Child maltreatment in the family context is a prevalent and pervasive phenomenon in many modern societies. The global perpetration of child abuse and neglect stands in stark contrast to its almost universal condemnation as exemplified in the United Nation’s Convention on the Rights of the Child. Much work has been devoted to the task of prevention, yet a grand synthesis of the literature is missing. Focusing on two core elements of prevention, that is, antecedents for maltreatment and the effectiveness of (preventative) interventions, we performed an umbrella review of meta-analyses published between January 1, 2014, and December 17, 2018. Meta-analyses were systematically collected, assessed, and integrated following a uniform approach to allow their comparison across domains. From this analysis of thousands of studies including almost 1.5 million participants, the following risk factors were derived: parental experience of maltreatment in his or her own childhood (d = .47), low socioeconomic status of the family (d = .34), dependent and aggressive parental personality (d = .45), intimate partner violence (d = .41), and higher baseline autonomic nervous system activity (d = .24). The effect size for autonomic stress reactivity was not significant (d = −.10). The umbrella review of interventions to prevent or reduce child maltreatment showed modest intervention effectiveness (d = .23 for interventions targeting child abuse potential or families with self-reported maltreatment and d = .27 for officially reported child maltreatment cases). Despite numerous studies on child maltreatment, some large gaps in our knowledge of antecedents exist. Neurobiological antecedents should receive more research investment. Differential susceptibility theory may shed more light on questions aimed at breaking the intergenerational transmission of maltreatment and on the modest (preventive) intervention effects. In combination with family-based interaction-focused interventions, large-scale socioeconomic experiments such as cash transfer trials and experiments with vouchers to move to a lower-poverty area might be tested to prevent or reduce child maltreatment. Prevalence, antecedents, and preventive interventions of prenatal maltreatment deserve continuing scientific, clinical, and policy attention.     

Risk factors for recurrence of maltreatment: a systematic review

Background

Children who have been maltreated are at increased risk of further maltreatment. Competent identification of those at highest risk of further maltreatment is an important part of safe and effective practice, but is a complex and demanding task.

Aim

To systematically review the research base predicting those children at highest risk of recurrent maltreatment.

Methods

Systematic review of cohort studies investigating factors associated with substantiated maltreatment recurrence in children.

Results

Sixteen studies met the inclusion criteria. The studies were heterogeneous. A variety of forms of maltreatment were considered. Four factors were most consistently identified as predicting future maltreatment: number of previous episodes of maltreatment; neglect (as opposed to other forms of maltreatment); parental conflict; and parental mental health problems. Children maltreated previously were approximately six times more likely to experience recurrent maltreatment than children who had not previously been maltreated. The risk of recurrence was highest in the period soon after the index episode of maltreatment (within 30 days), and diminished thereafter.

Conclusions

There are factors clearly associated with an increased risk of recurrent maltreatment, and these should be considered in professional assessments of children who have been maltreated. A comprehensive approach to risk assessment, including but not solely based on these factors, is likely to lead to interventions which offer greater protection to children.     

The epidemiology of child maltreatment

Child maltreatment is a significant worldwide problem, with consequences that can include impaired physical and mental health throughout life, and adverse social and occupational effects that carry a heavy economic and social burden. One estimate of cost to the US economy in 2007, for example, was over US$100bn. In middle- and low-income countries, there have been fewer studies of incidence and prevalence, and the economic and social costs are harder to estimate. It is very difficult to obtain full case ascertainment even in the most severe forms of child maltreatment, and even for fatal cases. In general, self-reporting and surveys identify higher rates of child maltreatment than data from sources relating to official notification. This paper reviews the epidemiology of child maltreatment from a practical perspective, with a focus on factors in the social environment, and the clinical history and examination, that predict an increased risk of child maltreatment.     

The burden of childhood cancer in Mexico: Implications for low‐ and middle‐income countries

In Mexico, childhood cancer incidence and mortality have increased in the last decade. Through government actions since 2005, the Popular Medical Insurance (PMI) program for childhood cancer was created. The objective of PMI was to offer early cancer diagnosis, standardized treatment regimens, and numerous pediatric oncology residency programs. It has also accredited 55 national hospitals for the care of these children. Current problems still present under the PMI include shortage of pediatric oncologists and nurses and high rate of abandonment of treatment. Our aim is to describe the current scenario of childhood cancer care in Mexico, especially from the perspective of the PMI and how it has impacted human resources, infrastructure, and medical education.     

Annual Research Review: Rethinking childhood trauma-new research directions for measurement,study design and analytical strategies

Childhood trauma is a key modifiable risk factor for psychopathology. Despite significant scientific advances, traumatised children still have poorer long-term outcomes than nontraumatised children. New research paradigms are, thus, needed. To this end, the review examines three dominant assumptions about measurement, design and analytical strategies. Current research warns against using prospective and retrospective measures of childhood trauma interchangeably; against interpreting cross-sectional differences in putative mediating mechanisms between adults with or without a history of childhood trauma as evidence of longitudinal changes from pre-trauma conditions; and against directly applying explanatory models of resilience or vulnerability to psychopathology in traumatised children to forecast individual risk in unseen cases. The warnings equally apply to research on broader measures of adverse childhood experiences (ACEs). Further research examining these assumptions can generate new insights on how to prevent childhood trauma and its detrimental effects.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.     

The impact of body weight trajectory from childhood on chronic inflammation in adulthood: The Bogalusa Heart Study

Importance::The impact of long-term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described.Objec...     

Initial P-glycoprotein expression in childhood acute lymphoblastic leukemia: no evidence of prognostic impact in follow-up

Treatment results in childhood acute lymphoblastic leukemia (ALL) have improved remarkably during the past 20 years, but still 25% of children cannot be permanently cured. Drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is the P-glycoprotein (P-gp)-mediated multiple-drug resistance (MDR). The authors prospectively analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a population-based series of 103 children with ALL treated according to intensive Nordic ALL protocols. Increased P-gp expression was detected in 55 patients (53%). With a cutoff value of 1% P-gp-positive blasts in bone marrow, no difference was found in event-free survival (EFS) or overall survival between children with low vs. increased P-gp expression. The 4-year EFS in the whole series was 77%. Patients with T-ALL had higher P-gp levels than the others, 3.6% vs. 1.0% (p = .002). P-gp expression did not correlate with the white blood cell count, age, sex, or cytogenetics. The authors conclude that the level of P-gp expression cannot be used as a tool for treatment stratification in childhood ALL.     

Prognostic impact of bone marrow karyotype in childhood acute lymphoblastic leukaemia: Swedish experiences 1986-91

Abstract The prognostic value of cytogenetic classification in acute lymphoblastic leukaemia (ALL) was evaluated in Swedish children below 16 years of age ( n = 372) diagnosed between 1986 and 1991. A bone marrow karyotype was obtained in 281 cases, of which 149 (53%) showed clonal abnormalities. Event-free survival (p-EFS) was 0.64–0.69 in patients with diploid and pseudodiploid karyotype. Patients with massive hyperdiploidy (> 50 chromosomes) had the best outcome (p-EFS = 0.76) and those with hypodiploidy (< 46 chromosomes) had the worst (p-EFS = 0.33). White blood cell count and age were the strongest predictors of outcome. The karyotype reached borderline significance. The diagnostic karyotype was also a predictor of outcome after relapse, with hyperdiploid patients doing better than the others. The presence of a structural chromosomal abnormality did not constitute a negative prognostic factor when intensive chemotherapy was given.     

The effect of childhood maltreatment on adult criminality: a tobit regression analysis

This article reports on the results of an analysis of a data set containing information on 667 nonmaltreated and 908 maltreated children. The data also contain information on whether the study subjects were arrested in early adulthood. Because adult arrests are an imperfect and censored measure of antisocial behavior, tobit regression analysis was used to examine the effect of the subjects' experiences of child maltreatment on later arrests while controlling for those subjects' demographic characteristics. The analysis finds that children's age, race, and sex and experiences of child neglect all have an impact on subsequent adult arrests. However, physical abuse and sexual abuse do not emerge as statistically significant predictors of arrests in this model. The study also illustrates a method for the decomposition of tobit coefficients to extract more information from them.     

多重RT-PCR检测儿童急性淋巴细胞白血病融合基因的临床研究

目的研究急性淋巴细胞白血病（ALL）患儿染色体畸变所致融合基因与临床危险度分层及治疗的关系。方法采用多重RT-PCR方法检测儿童ALL的常见融合基因,结合染色体核型分析、免疫表型及临床资料对152例ALL患儿进行临床研究。结果152例ALL患儿中有43例（29．5％）具有9种常见融合基因表达,包括 TEL/AML1、BCR/ABL（P190）、BCR/ABL（P210）、E2A/PBX1、MLL/ENL、MLL/AF9、TLS/ERG、CBF/MYH11、Hox11。TEL/AML1融合基因阳性23例,其中1例放弃治疗,1例因早期治疗反应不良,评估为高危,其他21例均早期治疗反应良好,目前停药10例（停药时间4～30个月）,11例仍为完全缓解（CR）,1例停药18个月后骨髓复发。E2A/PBX1融合基因阳性4例,其中3例评估为中危,目前均CR中,1例因早期治疗反应不良,评估为高危,化疗过程中复发死亡;BCR/ABL（P190）阳性5例,BCR/ABL（P210）阳性3例,其中5例行骨髓移植治疗（4例移植后数月骨髓复发,1例CR中）,1例选择高危方案化疗后骨髓复发,另外2例临床未缓解,放弃治疗;MLL基因阳性2例,均评估为中危,1例MLL/AF9,经强化疗后目前已停药18个月,1例MLL/ENL,在化疗过程中复发,放弃治疗;TLS/ERG融合基因1例,早期治疗反应不良,经强化疗后达CR,目前已停药20个月;Hox11融合基因阳性4例,均评估为中危,化疗后3例CR中,1例因复发放弃治疗。结论 TEL/AML1表达者化疗效果良好;BCR/ABL、MLL基因重排等化疗效果差,需骨髓移植或强烈化疗。采用多重RT-PCR方法可快速同时检测儿童急性白血病29种常见融合基因,完善白血病的MICM分型、指导临床个体化治疗。     

Effects of interventions for promoting physical activity during recess in elementary schools: a systematic review

ObjectiveSummarize the effects of interventions designed to promote physical activity during elementary school recess in children between 5 and 10 years old. Effective school interventions for children can promote physical activity and healthy behaviors.MethodsPubMed, Scopus, Bireme, SciELO, Web of Science, PsychINFO, Proquest, Physical Education Index, Sports Discus, and Eric databases were included in the data search. Original intervention articles on physical activity that used regression methods, published between 2000 and 2019 in English, Portuguese and Spanish were analyzed. Analyses were performed in 2019. Outcomes were organized according to the direction of the association by independent variables. Ten articles were considered eligible for data extraction and evaluation.ResultsSeveral strategies were used including playground markings, demarcation of physical activities zones, group activities, availability of sports equipment and facilities. Most of the studies were conducted in the United States. Recess periods ranged from 20–94 min per day and intervention time ranged from 6 weeks to 2 years. Recess duration and intervention effects were positively associated with physical activity. Gender (girls) and age (oldest) were negatively associated with physical activity during recess.ConclusionsInterventions based on modifications of school environment such as playground markings demarcation of physical activities zones, group activities, availability of sports equipment and facilities are cheap and cost-effective for increasing physical activity in school recess.     

The late consequences of anthracycline treatment on left ventricular function after treatment for childhood cancer

The purpose of this study was to determine the incidence of changes in left ventricular function in patients in long-term remission after treatment with anthracyclines for a childhood malignancy. The authors examined 155 patients in disease remission who underwent treatment protocols utilising anthracyclines in childhood. The group comprised 90 males and 65 females aged 15±4.9 years (range 5–29 years, median 15 years). The age at the time of diagnosis and start of treatment was 8.6±4.9 years (range 1–18 years, median 8 years). The time of follow-up was 7.3±4 years (range 1–21 years, median 6.3 years). The patients were given a cumulative dose of doxorubicin or daunorubicin of 250±131 mg/m² (range 50–1200 mg/m², median 240 mg/m²). The values of ejection fraction below 55% and fractional shortening below 30% assessed by means of echocardiography were considered as pathological. The control group consisted of 41 volunteers. Pathological values of fractional shortening were found in 12 patients (8%). Only one patient (0.64%) showed the development of heart failure due to cardiomyopathy. The group of the patients after chemotherapy revealed significantly worse values of left ventricular endsystolic wall stress, mean velocity of circumferential fibre shortening, Tei index, and isovolumic relaxation period in comparison with the control group. We found a correlation between the given cumulative dose of anthracyclines and indicators of systolic function of the left ventricle, but not a relation to the time indicators (age at diagnosis, time of follow-up). Conclusion:in the mean period of 6 years after chemotherapy, subclinical cardiotoxicity was found in 11 patients (7%) and cardiomyopathy with heart failure in one patient. Further indicators of subclinical damage are elevation of afterload (end-systolic stress), impaired relaxation and increased value of the Doppler index of global left ventricular function. Further monitoring and evaluation of the relevant subclinical abnormalities over a longer period of time are needed.Abbreviations CD cumulative dose - DT deceleration time - E/A index of the diastolic filling of the left ventricle - EF ejection fraction - ESS end-systolic stress - FS fractional shortening - HR heart rate - IRT isovolumic relaxation time - LV left ventricle - LVPWDd end-diastolic diameter of the left ventricular posterior wall - LVPWex excursion of the left ventricular posterior wall - LVPWP percentage of the systolic thickening of the left ventricular posterior wall - MPI myocardial performance index - mVcf _c mean velocity of circumferential fibre shortening     

Paroxysmal tonic upgaze of childhood: effect of age-of-onset on prognosis

Paroxysmal tonic upgaze (PTU) is a syndrome of childhood manifesting as sudden ocular movements with sustained upward deviation of the eyes. We describe the outcome of 6 patients, after a follow-up of 10 years, with onset of the disease in childhood. The aims of this study were to clarify some clinical features of this syndrome and to evaluate the long-term prognosis of these children. In all the patients, tonic upgaze episodes disappeared with time to remission, varying from 1 to 4 y, without any therapy and without any change in psychomotor development, EEG and neuroimaging. Only one child had pathologic interictal EEG with temporo-occipital spikes, which persisted after the offset of the disease. CONCLUSION: From a long-term follow-up, we can confirm the good prognosis of PTU and suggest it is possible to define a distinct syndrome of childhood without any neurological abnormalities and with spontaneous resolution.     

Interaction of dopamine transporter (DAT1) genotype and maltreatment for ADHD: a latent class analysis

Background: Although the association of the dopamine transporter (DAT1) gene and attention‐deficit/hyperactivity disorder (ADHD) has been widely studied, far less is known about its potential interaction with environmental risk factors. Given that maltreatment is a replicated risk factor for ADHD, we explored the interaction between DAT1 and maltreatment with ADHD symptoms defined dimensionally and using latent class analysis (LCA). Method: We tested the association of the 40 base‐pair variable number of tandem repeats polymorphism in DAT1, maltreatment, and their interaction in 2,488 boys and girls from the National Longitudinal Study of Adolescent Health. Results: In boys, ADHD symptoms were optimally defined by four classes (Combined, Hyperactive/Impulsive, Inattentive, and Normal), whereas in girls, ADHD symptoms were defined by three classes (Combined, Combined‐Mild, Normal). A significant DAT1 × maltreatment interaction revealed that maltreated girls homozygous for the 10‐repeat allele had more symptoms of ADHD, and were also 2.5 times more likely to be classified in the Combined ADHD group than in the Normal Group. Conclusions: The underlying structure of ADHD symptoms differed between boys and girls and DAT1 interacted with maltreatment to predict ADHD symptoms and ADHD status derived from LCA. Interactive exchanges between maltreatment and DAT1 for ADHD symptoms, and their implications for intervention, are discussed.     

死亡结构域相关蛋白和E2启动子结合因子在儿童急性白血病中的表达及其临床意义

目的探讨死亡结构域相关蛋白(Daxx)和E2启动子结合因子-1(E2F1)在急性白血病(AL)患儿骨髓细胞中的表达及其临床意义。方法采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(streptavidin peroxidase,SP)法,分别检测40例AL患儿和20例非恶性血液病儿童Daxx和E2F1的表达情况。结果 (1)AL组患儿骨髓细胞Daxx和E2F1阳性表达率分别为40%和57.5%,均显著高于对照组的10%(P<0.05)和20%(P<0.01);Daxx表达水平在急性髓细胞白血病组(58.8%)明显高于急性淋巴细胞白血病组(26.1%,P<0.05);E2F1在两组患儿中的阳性表达率差异无显著性(P>0.05)。(2)Daxx表达阴性者的完全缓解率高于阳性者(P<0.05),但E2F1表达阳性者与阴性者的完全缓解率相比差异无显著性(P>0.05)。(3)AL患儿Daxx与E2F1的表达水平有相关关系(P<0.05)。结论 Daxx和E2F1在儿童急性白血病中高水平表达,在儿童急性白血病的发生发展过程中可能存在某种协同作用,可能与儿童AL的疗效及预后相关。