The brain, with its astronomically complex interconnections and lifelong plasticity, self-assembles using a restricted instruction set of genes. Random processes, physical principles, and the DNA instruction set guide the formation of molecular interactomes and neuronal connectomes. Our selves, like a murmuration of birds, are composed of interactions of individual elements with their own intrinsic life and purpose, the individual elements being replaceable.

AbstractBackgroundInstitutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s –we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).MethodsAdult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously institutionalized adoptees (mean age = 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age = 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires.ResultsEarly institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory.ConclusionsThese results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms.

The Annual Review of Developmental Psychology presents a conversation with Professor Sir Michael Rutter, held remotely in the time of COVID but nonetheless wonderfully revealing of who this incredible scholar is and how he thinks. The contributions he has made to our understanding of child development are so vast and varied as to almost defy description. Erudite, articulate, and rigorous in his science, Michael Rutter is also deeply compassionate, caring, and outcome oriented. With training in medicine, neurology, pediatrics, and psychiatry, he held the first child psychiatry appointment in the United Kingdom and set up both the MRC Child Psychiatry Research Unit and the MRC Social, Genetic & Developmental Psychiatry Centre (SGDP). Unfortunately, Sir Michael passed away on October 23, 2021 while this article was in press. We feel fortunate to have had the opportunity to get to know Sir Michael, and to share this interview with you.

Background: Childhood institutional deprivation is associated with growth stunting in childhood but long-term effects in adulthood remain uncertain. Objective: To examine the impact of global institutional deprivation experienced in early childhood on subsequent growth with a special focus on final adult height and puberty timing. Participants & setting: The study was originally set in the UK, though some adoptive families lived abroad by the time of the adult follow up. 165 individuals adopted by UK families before 43 months of age from Romanian orphanages after the fall of the Ceausescu regime in the early 1990's were compared to 51 non-deprived UK adoptees, adopted before the age of 6 months. Methods: The English and Romanian Adoptees (ERA) study is a 20-year longitudinal natural experiment on the effects of institutional deprivation on development. Key growth milestones were extracted from growth curve modelling of height data collected at ages 4, 6, 11, 15 and 23 years using a Bayesian approach to fit the JPA2 model. Results: Deprivation effects on height were present at the take-off point of accelerating adolescent growth and persisted into adulthood - the largest effects being for individuals who experienced over six months of deprivation. Deprivation was associated with earlier take-off and achievement

Beginning in the 1960s, the Isle of Wight studies were among the first to investigate developmental reading problems in representative, population-based samples, using the tools of epidemiology. In this paper, we provide an overview of the contribution of the Isle of Wight studies to research on reading disabilities. We begin with an account of the surveys of primary school children, then move on to describe the programme of epidemiological and longitudinal research that flowed from them. The early studies provided some of the first systematic evidence on the extent and correlates of severe developmental reading problems, and their overlaps with other childhood difficulties. Subsequent studies documented the persistence of early reading problems into adolescence; provided comparative data on rates of reading problems in an inner city area; and most recently explored the long-term persistence of literacy problems up to mid-life.

BackgroundUsing data from the English & Romanian Adoptees (ERA) study, we recently reported that early time‐limited exposure to severe institutional deprivation is associated with early‐onset and persistent neurodevelopmental problems and later‐onset emotional problems. Here, we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early‐appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress.MethodsThe ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self‐reports; young adults also completed measures of stress reactivity, exposure to adverse life events, and functioning in work and interpersonal relationships.ResultsThe path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity, and emotional problems were inconclusive.ConclusionsOur analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model.

Using data from the English & Romanian Adoptees (ERA) study, we recently reported that early time-limited exposure to severe institutional deprivation is associated with early -onset and persistent neurodevelopmental problems and later -onset emotional problems. Here, we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity, exposure to adverse life events, and functioning in work and interpersonal relationships. The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity, and emotional problems were inconclusive. Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model.

There is an enormous interest in identifying the causes of psychiatric disorders but there are considerable challenges in identifying which risks are genuinely causal. Traditionally risk factors have been inferred from observational designs. However, association with psychiatric outcome does not equate to causation. There are a number of threats that clinicians and researchers face in making causal inferences from traditional observational designs because adversities or exposures are not randomly allocated to individuals. Natural experiments provide an alternative strategy to randomized controlled trials as they take advantage of situations whereby links between exposure and other variables are separated by naturally occurring events or situations. In this review, we describe a growing range of different types of natural experiment and highlight that there is a greater confidence about findings where there is a convergence of findings across different designs. For example, exposure to hostile parenting is consistently found to be associated with conduct problems using different natural experiment designs providing support for this being a causal risk factor. Different genetically informative designs have repeatedly found that exposure to negative life events and being bullied are linked to later depression. However, for exposure to prenatal cigarette smoking, while findings from natural experiment designs are consistent with a causal effect on offspring lower birth weight, they do not support the hypothesis that intra-uterine cigarette smoking has a causal effect on attention-deficit/hyperactivity disorder and conduct problems and emerging findings highlight caution about inferring causal effects on bipolar disorder and schizophrenia.

The concept of maternal deprivation placed emphasis on the risks associated with institutional care, but it is clear from comparative studies that the main risks probably stem from rearing in institutions that involve gross global deprivation as well as a lack of individualized care. J. Tizard, I. Sinclair, and R. V. G. Clark studied a range of different institutions catering for young people and drew attention to the importance of the distinction between child-oriented rearing practices and task-oriented rearing practices. Child-oriented rearing focused attention on trying to individualize the care of children according to their age and needs. The Romanian study concerned the long-term effects of early institutional care that involved profound deprivation in a total sample of children who were adopted by the age of 3.5 years. The studies of adoption by gay fathers and lesbian mothers have been very useful in showing that the quality of the rearing environment matters more than the particular family structure.

BACKGROUND AND OBJECTIVE: There is a well-documented association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD). The degree to which this reflects causal intrauterine effects or is due to unmeasured confounding is not clear. We sought to compare the association between maternal smoking during pregnancy and offspring ADHD with the associations with paternal smoking, grandmother’s smoking when pregnant with mother, and maternal smoking in previous pregnancies. Each of these exposures is expected to be influenced by much of the same confounding factors as maternal smoking during pregnancy, but cannot have direct intrauterine effects. A sibling control design was also used. METHODS: The current study used data from the Norwegian Mother and Child Cohort Study (n > 100 000 children). Mothers and fathers reported on smoking during pregnancy, and mothers reported on smoking in previous pregnancies and their mother’s smoking when pregnant with them. Mothers reported on child ADHD symptoms at 5 years of age. Information about child ADHD diagnosis was obtained from the Norwegian Patient Registry. RESULTS: Maternal smoking during pregnancy was not more strongly associated with offspring ADHD diagnosis than was paternal smoking, grandmother’s smoking when pregnant with mother, or maternal smoking in previous pregnancies. Sibling control analyses showed no association between maternal smoking in pregnancy and child ADHD symptoms among siblings discordant for maternal smoking. CONCLUSIONS: These results suggest that the association between maternal smoking during pregnancy and offspring ADHD is not due to causal intrauterine effects, but reflects unmeasured confounding.

Background Time-limited, early-life exposures to institutional deprivation are associated with disorders in childhood, but it is unknown whether effects persist into adulthood. We used data from the English and Romanian Adoptees study to assess whether deprivation-associated adverse neurodevelopmental and mental health outcomes persist into young adulthood.Methods The English and Romanian Adoptees study is a longitudinal, natural experiment investigation into the long-term outcomes of individuals who spent from soon after birth to up to 43 months in severe deprivation in Romanian institutions before being adopted into the UK. We used developmentally appropriate standard questionnaires, interviews completed by parents and adoptees, and direct measures of IQ to measure symptoms of autism spectrum disorder, inattention and overactivity, disinhibited social engagement, conduct or emotional problems, and cognitive impairment (IQ score <80) during childhood (ages 6, 11, and 15 years) and in young adulthood (22-25 years). For analysis, Romanian adoptees were split into those who spent less than 6 months in an institution and those who spent more than 6 months in an institution. We used a comparison group of UK adoptees who did not experience deprivation. We used mixed-effects regression models for ordered-categorical outcome variables to compare symptom levels and trends between groups.Findings Romanian adoptees who experienced less than 6 months in an institution (n=67 at ages 6 years; n=50 at young adulthood) and UK controls (n=52 at age 6 years; n=39 at young adulthood) had similarly low levels of symptoms across most ages and outcomes. By contrast, Romanian adoptees exposed to more than 6 months in an institution (n=98 at ages 6 years; n=72 at young adulthood) had persistently higher rates than UK controls of symptoms of autism spectrum disorder, disinhibited social engagement, and inattention and overactivity through to young adulthood (pooled p<0.0001 for all). Cognitive impairment in the group who spent more than 6 months in an institution remitted from markedly higher rates at ages 6 years (p=0.0001) and 11 years (p=0.0016) compared with UK controls, to normal rates at young adulthood (p=0.76). By contrast, self-rated emotional symptoms showed a lateonset pattern with minimal differences versus UK controls at ages 11 years (p=0.0449) and 15 years (p=0.17), and then marked increases by young adulthood (p=0.0005), with similar effects seen for parent ratings. The high deprivation group also had a higher proportion of people with low educational achievement (p=0.0195), unemployment (p=0.0124), and mental health service use (p=0.0120, p=0.0032, and p=0.0003 for use when aged <11 years, 11-14 years, and 15-23 years, respectively) than the UK control group. A fifth (n=15) of individuals who spent more than 6 months in an institution were problem-free at all assessments.Interpretation Notwithstanding the resilience shown by some adoptees and the adult remission of cognitive impairment, extended early deprivation was associated with long-term deleterious effects on wellbeing that seem insusceptible to years of nurturance and support in adoptive families.

Neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder, although most commonly considered in childhood, can be lifelong conditions. In this Personal View that is shaped by clinical experience and research, we adopt a conceptual approach. First, we discuss what disorders are neurodevelopmental and why such a grouping is useful. We conclude that both distinction and grouping are helpful and that it is important to take into account the strong overlap across neurodevelopmental disorders. Then we highlight some challenges in bridging research and clinical practice. We discuss the complexity of clinical phenotypes and the importance of the social context. We also argue the importance of viewing neurodevelopmental disorders as traits but highlight that this is not the only approach to use. Finally, we consider developmental change across the life-span. Overall, we argue strongly for a flexible approach in clinical practice that takes into consideration the high level of heterogeneity and overlap in neurodevelopmental disorders and for research to link more closely to what is observed in real-life practice.

Infantile autism is a severe disorder of development which was first described systematically by Kanner. This chapter describes the methods used in a study designed to compare the effects of three different approaches to the education of autistic children. It focuses on the issues involved in the measurement of staff-child interaction in units for children with severe developmental handicaps, rather than on the progress of the children. In assessing the utility of measures of interaction it is important to know that there were major differences between the units in the progress of the children. The special units which had been set up for autistic children in the United Kingdom varied considerably in their theoretical orientation, emphasis on formal teaching, degree of structure, segregation or mixing with other children, and in the type of relationship the staff provided for the children.

Background Early-life institutional deprivation produces disinhibited social engagement (DSE). Portrayed as a childhood condition, little is known about the persistence of DSE-type behaviours into, presentation during, and their impact on, functioning in adulthood. Aims We examine these issues in the young adult follow-up of the English and Romanian Adoptees study. Method A total of 122 of the original 165 Romanian adoptees who had spent up to 43 months as children in Ceauşescu's Romanian orphanages and 42 UK adoptees were assessed for DSE behaviours, neurodevelopmental and mental health problems, and impairment between ages 2 and 25 years. Results Young adult DSE behaviour was strongly associated with early childhood deprivation, with a sixfold increase for those who spent more than 6 months in institutions. However, although DSE overlapped with autism spectrum disorder and attention-deficit hyperactivity disorder symptoms it was not, in itself, related to broader patterns of mental health problems or impairments in daily functioning in young adulthood. Conclusions DSE behaviour remained a prominent, but largely clinically benign, young adult feature of some adoptees who experienced early deprivation.

Hypothalamic pituitary adrenal (HPA) axis function is disrupted in institutionally-deprived children reduced morning cortisol, flattened diurnal slope and blunted reactivity persist even after successful adoption into positive family environments. Here we test whether such effects persist into adulthood. Cortisol release across the day (sampled at awakening, 30 and 45 min later, and at four points across the day) was investigated in young adult adoptees who had lived in severe deprivation for up to 43 months in early childhood in Ceauescu's Romanian orphanages and a comparison group of non-deprived UK adoptees (Total N = 57; mean age = 24 +/- 0.9 years). The mediating role of cortisol levels on adult mental health was examined using data from standardized clinical assessments. Cortisol profiles were disrupted in the Romanian adoptees who experienced more than 6 months deprivation marked by a striking absence of the cortisol awakening response (CAR) and a significantly flatter cortisol curve until 1 h 15 min after awakening. Whereas institutional deprivation was associated with both cortisol secretion and emergence of emotional problems in young adulthood, path analysis revealed no evidence for a mediating role of CAR disruption in the sub-sample studied here. The results are in line with findings of HPA axis hypo-functionality following early adverse experience and provide strong evidence for long-term programming effects of HPA axis function through experience of institutional deprivation.

Early-life institutional deprivation is associated with attention-deficit/hyperactivity disorder (ADHD) later in childhood and adolescence. In this article, we examine, for the first time, the persistence of deprivation-related ADHD into young adulthood in a sample of individuals adopted as young children by UK families after periods in extremely depriving Romanian orphanages. We estimated rates of ADHD at age 15 years and in young adulthood (ages 22–25 years) in individuals at low (LoDep; nondeprived UK adoptees and Romanian adoptees with less than 6-month institutional exposure) and high deprivation-related risk (HiDep; Romanian adoptees with more than 6-month exposure). Estimates were based on parent report using DSM-5 childhood symptom and impairment criteria. At age 15, data were available for 108 LoDep and 86 HiDep cases, while in young adulthood, the numbers were 83 and 60, respectively. Data on education and employment status, IQ, co-occurring symptoms of young adult disinhibited social engagement (DSE), autism spectrum disorder (ASD), cognitive impairment, conduct disorder (CD), callous-unemotional (CU) traits, anxiety, depression and quality of life (QoL) were also collected. ADHD rates in the LoDep group were similar to the general population in adolescence (5.6%) and adulthood (3.8%). HiDep individuals were, respectively, nearly four (19%) and over seven (29.3%) times more likely to meet criteria, than LoDep. Nine ‘onset’ young adult cases emerged, but these had a prior childhood history of elevated ADHD behaviours at ages 6, 11 and 15 years. Young adult ADHD was equally common in males and females, was predominantly inattentive in presentation and co-occurred with high levels of ASD, DSE and CU features. ADHD was associated with high unemployment and low educational attainment. We provide the first evidence of a strong persistence into adulthood of a distinctively complex and impairing deprivation-related variant of ADHD. Our results confirm the powerful association of early experience with later development in a way that suggests a role for deep-seated alterations to brain structure and function.

Translational research focuses on innovation in healthcare settings, but this is a two-way process that may have implications for either treatment or prevention. Smoking and lung cancer and the fetal alcohol syndrome are used as examples. Experimental medicine that budges basic and clinical science often constitutes a key way forward. Areas of scientific progress and challenge are discussed in relation to drug action, social cognition, cognitive neuroscience, molecular genetics, gene-environment interaction, and epigenetics. Key concepts and challenges in relation to stress include toxicity, allostatic load, the hypothalamus-pituitary-adrenal axis, and objectives versus subjective stress. The reasons for the need to test causal inferences are discussed. Various kinds of natural experiments are discussed in illustration using the assisted conception design, the discordant monozygotic twin design, and the study of universal exposure. Animal models are discussed in relation to enrichment and deprivation effects and the effects of infant separation experiences, epigenetic effects, and the biological embedding of experiences. Translational issues are discussed in relation to the hypothalamic-pituitary-adrenal axis, epigenetics, and inflammation. In conclusion, it is suggested that there are immediate possibilities for experimental medicine but caution is needed with respect to moving into translation too quickly.

The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD. A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins. The meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96–.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44–.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61–.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64–91%. Shared environmental effects became significant as the prevalence rate decreased from 5–1%: 07–35%. The DF analyses show that for the most part, there is no departure from linearity in heritability. We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.