Showing papers by "Michael Rutter published in 2007"

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Proceeding From Observed Correlation to Causal Inference: The Use of Natural Experiments

Abstract: This article notes five reasons why a correlation between a risk (or protective) factor and some specified outcome might not reflect environmental causation. In keeping with numerous other writers, it is noted that a causal effect is usually composed of a constellation of components acting in concert. The study of causation, therefore, will necessarily be informative on only one or more subsets of such components. There is no such thing as a single basic necessary and sufficient cause. Attention is drawn to the need (albeit unobservable) to consider the counterfactual (i.e., what would have happened if the individual had not had the supposed risk experience). Fifteen possible types of natural experiments that may be used to test causal inferences with respect to naturally occurring prior causes (rather than planned interventions) are described. These comprise five types of genetically sensitive designs intended to control for possible genetic mediation (as well as dealing with other issues), six uses of twin or adoptee strategies to deal with other issues such as selection bias or the contrasts between different environmental risks, two designs to deal with selection bias, regression discontinuity designs to take into account unmeasured confounders, and the study of contextual effects. It is concluded that, taken in conjunction, natural experiments can be very helpful in both strengthening and weakening causal inferences.

Early adolescent outcomes for institutionally-deprived and non-deprived adoptees. I: disinhibited attachment.

Abstract: Background: disinhibited attachment is an important sequel of an institutional rearing, but questions remain regarding its measurement, its persistence, the specificity of the association with institutional rearing and on whether or not it constitutes a meaningful disorder. Method: children initially reared in profoundly depriving institutions in Romania and subsequently adopted into UK families were compared with respect to findings at 11 years with children who had not experienced institutional deprivation and who had been adopted within the UK before the age of 6 months. Measures included parental reports, a Strange Situation procedure modified for use in the home and systematic standardised investigator ratings of the children's behaviour. Results: disinhibited attachment, as reported by parents, showed a high degree of persistence from 6 to 11, but also a reduction over time in its frequency. Investigator ratings validated the parental reports but suggested that much of the fall in rate of disinhibited attachment was a function of the parental measure being less developmentally appropriate at 11 than it had been at 6. Disinhibited attachment was strongly associated with institutional rearing but there was not a significant increase in relation to duration of institutional deprivation beyond the age of 6 months. Mild, but not marked, disinhibited attachment was quite frequent in non-institutionalised adopted children but both the course and correlates indicated that its meaning was probably quite different. In the institution-reared children, disinhibited attachment was associated with a marked increase in service usage and associations with other forms of psychopathology. Conclusions: disinhibited attachment constitutes a valid, and handicapping, clinical pattern that is strongly associated with an institutional rearing.

Effects of profound early institutional deprivation: An overview of findings from a UK longitudinal study of Romanian adoptees

Abstract: A randomly selected sample of 165 children from Romania (of whom 144 had been reared in institutions) who were adopted by UK families, with placement before the age of 42 months, was studied at 4, 6, and 11 years of age. Comparisons were made with a sample of 52 non-institutionalized UK children adopted before the age of 6 months, who were studied in the same way. The paper briefly summarizes circumstances at the time of adoption and then reports findings at age 11, focusing on changes between 6 and 11. Marked catch-up in psychological functioning was evident following adoption, but significant problems continued in a substantial minority of the children placed after the age of 6 months. The theoretical implications of the findings are considered, and the policy implications are noted.

Gene–environment interdependence

Abstract: Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene–environment interactions were usually of so little importance that they could safely be ignored. Theoretical considerations suggested that that was unlikely to be true and empirical findings are now accumulating on the demonstrated and replicated biological interactions between identified common single genetic variants and the operation of environmentally mediated risks. The paper outlines the evidence and considers why it is changing concepts in ways that matter.

Normality and impairment following profound early institutional deprivation: a longitudinal follow-up into early adolescence.

Abstract: Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K. adoptees placed before the age of 6 months. Specifically, the validity of the assessment, the degree of continuity and change in levels of functioning from 6 to 11 years, and the factors in the pre- and postadoption environment accounting for heterogeneity in outcome were examined. Pervasive impairment was significantly raised in children experiencing institutional deprivation for > or =6 months of life, with a minority within this group showing no impairment. There was no additional significant effect of duration of deprivation beyond the 6-month cutoff, and few other predictors explained outcome. The pattern of normality/impairment was mainly established by 6 years of age, with considerable continuity at the individual level between 6 and 11 years. The findings are discussed in terms of the possibility of a sensitive period for development.

Early Adolescent Outcomes of Institutionally Deprived and Non-Deprived Adoptees. III. Quasi-Autism.

Abstract: Background: Some young children reared in profoundly depriving institutions have been found to show autistic-like patterns, but the developmental significance of these features is unknown. Methods: A randomly selected, age-stratified, sample of 144 children who had experienced an institutional upbringing in Romania and who were adopted by UK families was studied at 4, 6, and 11 years, and compared with a non-institutionalised sample of 52 domestic adoptees. Twenty-eight children, all from Romanian institutions, for whom the possibility of quasi-autism had been raised, were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) at the age of 12 years. Results: Sixteen children were found to have a quasi-autistic pattern; a rate of 9.2% in the Romanian institution-reared adoptees with an IQ of at least 50 as compared with 0% in the domestic adoptees. There were a further 12 children with some autistic-like features, but for whom the quasi-autism designation was not confirmed. The follow-up of the children showed that a quarter of the children lost their autistic-like features by 11. Disinhibited attachment and poor peer relationships were also present in over half of the children with quasi-autism. Conclusions: The findings at age 11/12 years confirmed the reality and clinical significance of the quasi-autistic patterns seen in over 1 in 10 of the children who experienced profound institutional deprivation. Although there were important similarities with ‘ordinary’ autism, the dissimilarities suggest a different meaning. Despite the evidence that autism constitutes a disorder that is strongly influenced by genetic factors, patterns that appear similar to autism have been reported in both congenitally blind children (Brown, Hobson, & Lee, 1997) and in children exposed to profound early institutional deprivation (Hoksbergen, ter Laak, Rijk, vanDijkum, & Stoutjesdijk, 2005; Rutter et al., 1999). At 4 years of age, the pattern of autistic-like behaviour was indistinguishable from that seen in a prospectively studied sample of ‘ordinary’ children with autism investigated by Catherine Lord and her colleagues. By age 6 years, the quasi-autistic features in the sample of children from Romanian institutions had diminished and a number of atypical features were noted. The children showed more flexibility in communication than would ordinarily be expected with autism; several showed substantial social approach (albeit of an abnormal kind), and a few showed indiscriminately friendly behaviour of a kind that is more ordinarily associated with disinhibited attachment. Three of the children with quasi-autistic patterns were also severely mentally retarded, but the remainder were not. The quasi-autistic pattern seen in one girl was quite transient and it was regarded as not falling into the same group. Thus, the overall sample at that time comprised 3 children with quasi-autistic patterns associated with severe mental retardation, 7 with similar patterns that were not accompanied by severe retardation, and 1 child with a transient pattern who was excluded from further consideration. In addition there were another 10 cases on whom less information was available, who seemed to show milder quasi-autistic patterns. A systematic follow-up of this group of children was necessary in order to examine a number of outstanding issues concerning the meaning of the observed pattern. The original report commented on the high frequency of very marked circumscribed interests of a repetitive stereotyped pattern that had developed after the children had left institutions and joined their adoptive families. These interests made the picture rather different from the social deficits seen in severely deprived children within an institutional setting. We hypothesised that the impaired social relationships might have something in common with the so-called indiscriminate friendliness associated with disinhibited attachment seen in children who have experienced institutional rearing (Rutter et al., 2007), and the current follow-up tests the hypothesis that, by the time the children had reached age 11 years, the distinctively autistic features would have faded away and be replaced by disinhibited attachment disorder. Second, the quasi-autistic pattern might be a non-specific consequence of the cognitive impairment seen in some of the children. If so, the persistence of the quasi-autistic pattern should be evident only in those who showed cognitive impairment at age 11. Third, the profound deprivation might have led to an impairment in mentalising skills and in psychological perspective taking (see Frith, 2003), and that it was these features that had underpinned the quasi-autistic pattern. If so, any persistence of the quasi-autistic pattern should be confined to the children who showed such problems in social cognition. A further query was whether or not the quasi-autistic pattern constituted a categorically distinct syndrome or, rather, whether it was simply the end of a continuum of similar features seen in the institution-reared children as a whole. The follow-up of the children with milder features, together with the characteristics of the children with raised scores on the Social Communication Questionnaire (a scale devised to assess autistic-like features – Berument, Rutter, Lord, Pickles, & Bailey, 1999; Rutter, Bailey, & Lord, 2003a) should provide the answer. Because the possible association between institutional deprivation and autism became evident only after the study had started, the sampling for the children to be studied in detail at age 6 using standardised diagnostic instruments for autism was less thorough with the older children at the beginning of the study than it was later on. Therefore, a prior methodological point that needed to be dealt with before proceeding with the more substantive issues was whether or not cases with quasi-autistic features had been missed. Accordingly, for the follow-up at age 11 years, all children who received scores at or above 14 on the Social Communication Questionnaire (SCQ), and/or for whom any of the research assessments suggested the possibility of autism, were routinely included in the special follow-up sample.

Early Adolescent Outcomes of Institutionally-Deprived and Non-Deprived Adoptees. II: Language as a Protective Factor and a Vulnerable Outcome.

Abstract: Background: There is uncertainty about the extent to which language skills are part of general intelligence and even more uncertainty on whether deprivation has differential effects on language and non-language skills. Methods: Language and cognitive outcomes at 6 and 11 years of age were compared between a sample of 132 institution-reared Romanian children adopted into UK families under the age of 42 months, and a sample of 49 children adopted within the UK under the age of 6 months who had not experienced either institutional rearing or profound deprivation. Results: The effects of institutional deprivation were basically similar for language and cognitive outcomes at age 6; in both there were few negative effects of deprivation if it ended before the age of 6 months and there was no linear association with duration of deprivation within the 6 to 42 month range. For the children over 18 months on arrival (range 18–42 months), the presence of even very minimal language skills (imitation of speech sounds) at the time of arrival was a strong beneficial prognostic factor for language and cognitive outcomes, but not for social/emotional/behavioural outcomes. Individual variations in adoptive parent characteristics were unrelated to differences in language or cognitive outcomes, possibly as a consequence of the limited variability in the adoptive family group. Conclusions: Minimal language probably indexes some form of cognitive reserve that, in turn, indexes the degree of institutional deprivation.

Association between nonmaternal care in the first year of life and children's receptive language skills prior to school entry: the moderating role of socioeconomic status

Abstract: Background: Studies have suggested that nonmaternal care (NMC) may either carry risks or be beneficial for children’s language development. However, few tested the possibility that NMC may be more or less protective for children with different family backgrounds. This study investigates the role of the family environment, as reflected in the socioeconomic status (SES), in the association between NMC in the first year of life and children’s receptive language skills prior to school entry. Method: A representative sample of 2,297 Canadian children aged between 0 and 11 months at their first assessment was followed over 4 years. Receptive language skills were assessed with the Peabody Picture Vocabulary Test Revised (PPVT-R) when the child was 4 to 5 years old. Results: After controlling for selection factors, SES was found to moderate the association between NMC and receptive language skills: Fulltime NMC in the first year of life was associated with higher PPVT-R scores among children from low SES families (d ¼ .58), but not among children from adequate SES families. Conclusion: Full-time NMC in infancy may contribute to reducing the cognitive inequalities between children of low and adequate SES. Keywords: Language development, cognitive development, nonmaternal care, child-care, socioeconomicstatus,infancy. Abbreviations: NMC:nonmaternalcare;SES:socioeconomicstatus;PPVT-R: Peabody Picture Vocabulary Test Revised. Over the past two decades, considerable attention has been given to the role of nonmaternal care (NMC) experiencesinchildren’searlycognitiveandlanguage development.StudieshavesuggestedthatNMCinthe first year of life may either carry risks (Waldfogel, Han, & Brooks-Gunn, 2002) or be beneficial for children’s cognitive and language development (Andersson, 1992). Whereas some studies examined the features of NMC that may be related to its protective or detrimental impact, few tested the possibility that NMC may be more or less protective for children with different family backgrounds. Forinstance, NMC may be particularly beneficial for children who grow up in impoverished home environments. Conversely, NMC may be particularly detrimental for children who would otherwise benefit from an enriched home environment. Furthermore, the extent to which NMC may be beneficial or detrimental for subgroups of children may depend on the amount (e.g., part-time vs. full-time) of the experience. The general purpose of the present study was to examine the moderating role of socioeconomic status (SES) in the association between NMC in the first year of life and children’s receptive language skills prior to school entry. We refer to nonmaternal care (NMC) as the various forms of non-parental care experienced by preschool children (e.g., daycare centers, family daycare). The moderating role of SES

Scholastic Attainment Following Severe Early Institutional Deprivation: A Study of Children Adopted from Romania.

Abstract: The relationship between severe early institutional deprivation and scholastic attainment at age 11 in 127 children (68 girls and 59 boys) adopted from institutions in Romania was compared to the attainment of 49 children (17 girls and 32 boys) adopted within the UK from a non-institutional background. Overall, children adopted from Romania had significantly lower attainment scores than those adopted within the UK; the children within the Romanian sample who had spent 6 months or more in an institution had significantly lower attainment scores than those who had spent less than 6 months in an institution, but there was no additional risk of low attainment associated with longer institutional care after 6 months. The lower scholastic attainment in the children adopted from Romanian institutions, as compared with domestic adoptees, was mediated by IQ, and to a lesser degree, inattention/overactivity. When these factors were taken into account, only small between-group differences in attainment remained.

Etiological heterogeneity in the development of antisocial behavior: the Virginia Twin Study of Adolescent Behavioral Development and the Young Adult Follow-Up.

Abstract: Background. Longitudinal, genetically informed, prospective data collected on a large population of male twins (n = 1037) were used to examine developmental differences in the etiology of antisocial behavior. Method. Analyses were carried out on both mother- and child-reported symptoms of conduct disorder (CD) in 10- to 17-year-old twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and self-reported antisocial behavior by the twins as young adults from the Young Adult Follow-Up (YAFU) study. Results. The following trends were identified: (1) a single genetic factor influencing antisocial behavior beginning at age 10 through young adulthood ('life-course persistent'); (2) a shared-environmental effect beginning in adolescence ('adolescent-onset'); (3) a transient genetic effect at puberty; and (4) a genetic influence specific to adult antisocial behavior. Conclusions. Overall, these etiological findings are consistent with predictions from Moffitt's developmental theory of antisocial behavior. The genetic effect at puberty at ages 12-15 is also consistent with a genetically mediated influence on the timing of puberty affecting the expression of genetic differences in antisocial outcomes.

Psychopathological Development Across Adolescence

Abstract: Daniel Offer’s seminal writings in the 1960s led to a realization that normal adolescence was not characterized by turmoil and upheaval, the then prevailing view that derived from studies of clinical samples In this paper, the research findings that have appeared over the last four decades are reviewed with respect to the overall features of adolescence, the psychopathological changes in the teenage years, brain development during adolescence and neuroendocrine changes The possible pathways involved in adolescent transitions are considered with respect to depression, drug use/abuse, antisocial behavior, schizophrenia and suicidal behavior Conclusions are drawn on the operation of a range of multi-step causal pathways and implications for policy and practice are discussed

Communicative Openness About Adoption and Interest in Contact in a Sample of Domestic and Intercountry Adolescent Adoptees

Abstract: Adolescent intercountry (n = 122) and domestic (n = 40) adoptees and their adoptive parents were asked about their views on communicative openness. The adoptees were also asked for their thoughts o...

The Experience of Adoption (1)* A Study of Intercountry and Domestic Adoption from the child's point of view:

Abstract: Amanda Hawkins, Celia Beckett, Jenny Castle, Christine Groothues, Edmund Sonuga-Barke, Emma Colvert, Jana Kreppner, Suzanne Stevens and Michael Rutter compared views about adoption for two groups of 11-year-old children (n = 180). The team's analyses compared the views of children according to their pre-adoption background: UK domestic adoptees placed before the age of six months versus intercountry adoptees who had experienced extreme deprivation for up to three-and-a-half years in Romania prior to placement (the Romanian group was further broken down by age at placement). Remarkably few differences were found between these groups, with the exception of two areas. Older-placed adopted children from Romania were significantly more likely to find it difficult to talk about adoption than domestic adoptees, and to feel different from their adoptive families. However, supplementary analyses suggested that these differences were due to increased levels of difficulties within the older-placed Romanian group, rather than whether they were adopted internationally or domestically. The implications of the similarities and differences between these groups for policy and practice are discussed.