Virtual Issue: 'The Rutter Effect' – a Celebration of Professor Sir Michael

Journal of Child Psychology and Psychiatry

Virtual Issue: ‘The Rutter Effect’ – a celebration of Professor Sir Michael Rutter’s contributions to child psychology and psychiatry

This Virtual Issue celebrates Professor Sir Michael has been at the forefront of educating and guiding Rutter’s extraordinary contribution to child and the field to a thorough and integrated understanding adolescent psychology and psychiatry represented of the importance of the complex connections specifically by his writings published in the Journal between genes and environment in the development of Child Psychology and Psychiatry. It is published of psychopathology. as part of the JCPP’s 60th anniversary celebrations. A second key area of influence is covered in paper 4 Rutter has been, and remains, a towering influence (Rutter, Kim-Cohen, & Maughan, 2006; commentary in child and adolescent psychiatry – recognized as a, by Ramchandani) which argues for the importance of if not the, driving force in its transformation from understanding psychiatric disorders as developmen- what even in the 1960s and early 1970s remained a tal constructs and explains why it is so important to rather speculative and subjective endeavor into a understand precursors and pathways from early life fully fledged science. His influence has transcended risks to adult mental health. At the same time, this disciplinary boundaries to have a profound effect on paper refined and delineated many central concepts epidemiology, genetics, developmental psychology, in the field of developmental psychopathology, such social work, and social policy. The counter factual is as vulnerability, protection, resilience, developmental unthinkable – if Rutter had not existed – scientific turning points, and homotypic and heterotypic con- child psychiatry – at least as we know it now – would tinuity: concepts that we now take for granted. not have existed – his influence has been that Following on from that is paper 5 which includes an profound. Rutter’s is a distinctive and rare vision – elegant analysis written with Caspi and Moffitt (Rut- a theoretically sophisticated and clinically commit- ter, Caspi, & Moffitt, 2003; commentaries by both ted adherence to the logic of the scientific method – Klump and Oldehinkel) on how the study of sex driven by the conviction that only reason, grounded differences can be used to parse these sorts of in objective evidence, has the power to separate developmental psychopathological mechanisms. cultural myth about the nature and causes of mental A third theme, represented in our editors’ selec- disorder from clinical reality and drive forward tions, is early adversity and development – especially innovation in the care of children with mental health focusing on the profound effects of institutional care. problems. His intellectual clarity and focus, and Paper 6 therefore examines the outcomes of children tenacious questioning mind is something colleagues raised in UK institutions (Roy, Rutter, & Pickles, from all backgrounds have recognized and 2000; commentary by Gunnar). This is followed by applauded. At the heart of his distinctive form of one of two papers included in the Virtual Issues from creativity is his unparalleled ability to first dissect the natural experiment of the English and Romanian and then synthesize complex ideas and to express Adoptees (ERA) study whereby children spent vary- these with great precision in a way that makes them ing degrees of time in the brutally depriving envi- accessible to scientists and clinicians. Motivated by ronments of the Romanian orphanages and then a rigorous and tireless pursuit of the truth of the were suddenly moved to enriched environments in matter, that abjures the easy payoff or the low English adoptive families (Rutter et al., 2007; com- hanging fruit represented by a more simplistic mentary by Diaz-Stransky & Bloch). This study has empiricism. His form of rigorous conceptual analysis given the field a unique insight into the persistent must remain central to our field, especially in this risks associated with early adversity and the poten- age of enthusiasm for blind big data analytics. tial for developmental catch-up and has had an In total, Rutter has authored 120 JCPP papers and extraordinary impact on the field. counting – the first being published in 1965. Each of Rutter’s seminal contribution to advancing the the 11 papers in the Virtual Issue has been selected by characterization of childhood disorders in general one of our editor colleagues and is accompanied by and autism in particularly is highlighted by the next their reflection on what that work has meant to them two-paper theme. These papers complement each and to the science of child psychology and psychiatry. other beautifully. Paper 8 was a ground-breaking The first three papers illustrate Rutter’s extensive twin study demonstrating for the first time the work on gene–environment interplay (Rutter, Moffitt, striking heritability of autism (Folstein & Rutter, & Caspi, 2006; Rutter, Silberg, O’Connor, & Simon- 1977; comentary by Fombonne). Paper 9, the second off, 1999a, 1999b; commentaries by Gregory & paper from the ERA study, delineated for the first Jaffee). These seminal reviews show how Rutter time a variant of autism-like psychopathology whose

© 2019 Association for Child and Adolescent Mental Health Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA 2 virtual issue origins appear to be environmental in nature and topic of the day: the interplay between genes and the linked to profound deprivation (Rutter et al., 1999; environment – and the focus of the paper on which I commentary by Green). Paper 10 illustrates further am writing this commentary. The paper I have Rutter’s enormous breadth of impact on classifica- selected (Rutter, Moffit & Caspi, 2006) was published tion and measurement – this time in relation to just a few years after the human genome had been disorders of language. In relation to this, we include sequenced and the buzz in the field was palpable. a classic 1975 paper with Professor Yule (Rutter & Together with Professors Avshalom Caspi and Terrie Yule, 1975; commentary by Halperin). Moffitt, he was helping to move the field on from the A characteristic of Rutter’s work has been his furious ‘nature vs nurture’ debate and instead unstinting commitment to bringing data to challenge attempting to further understand and explain the preconceived cultural notions of what constitutes interplay between the two influences. Anyone in optimal or good enough parenting. This has covered doubt about the relationship between genes and the issues relating to maternal deprivation, institutional environment might want to consider how people care, divorce, and nontraditional families. The final behave in response to stress (i.e., clearly an environ- paper (paper 11) illustrates this very well in relation mental influence), such as exams. There are those to parenting and child rearing in same-sex couples who take a metaphorical walk in the park, and others (Golombok, Spencer, & Rutter, 1983; commentary who suffer greatly with anxiety, insomnia, and other by Sitkin Zelin and Bloch). difficulties. Some of these differences in responses to Overall, these selections testify to the staggering environmental challenge are due to genetic variations breadth of Rutter’s vision and the level of scientific between people. impact he has had on the field. Rereading them is In this seminal review, the authors start by contex- humbling and inspiring – yet they cover only about half tualizing the topic historically and present core con- the domains where Rutter’s influence has been felt. In cepts that remain essential. They discuss the a second Virtual Issue, planned for later in the year, we multifactorial origin of most disorders, and note that will extend the scope of our review to illustrate Rutter’s risks are ‘probabilistic, rather than deterministic’. enormous impact on areas such as psychiatric epi- They also outline the different ways in which genes demiology (e.g., the Isle of Wight study), conceptual- and the environment act in concert – describing gene– izing attachment, assessment and measurement environment interactions and correlations and dis- (Rutter scale, SCQ, ADOS), nosology and classification cussing epigenetic mechanisms. They refer to studies (ICD + DSM) and the effects of education. that are seminal in the field, including rat studies by Finally, we had the pleasure of corresponding with Michael Meaney, demonstrating the effects of parent- Professor Rutter about this Virtual Issue, and he was ing on gene expression and stress response in off- at pains to emphasize that all his accomplishments spring. The authors draw upon rich and varied would not have been possible without the support literature to illustrate their points – and in doing so and collaboration of the excellent colleagues he has highlight that single designs alone are often insuffi- had the good fortune to work with over the years. cient to address complex questions and multiple Enjoy this Virtual Issue as you join with us to study designs remain optimal. Fast-forward a decade celebrate the extraordinary achievements of this or so and, as with all genetic research conducted in remarkable scientist and clinician. that era, understanding has moved on as have the methodologies used to address questions. Instead of focusing on candidate genes using modest sample sizes, genome-wide association studies are conducted Paper 1: Gene–environment interplay and on samples that sometimes exceed a million partici- psychopathology: multiple varieties but real pants (e.g., Jansen et al., 2018). The authors of this effects – Rutter, Moffitt and Caspi (2006) seminal paper changed our thinking about genes and Commentator – Alice Gregory, Goldsmith’s the environment. This topic is not out of vogue, but University, UK there seems to be a partial pause in research focused Professor Michael Rutter has set the bar for research- on gene–environment interplay focusing on psychi- ers of child psychiatry of my generation. His work has atric traits. Some in the field await polygenetic risk made such an impact that he was awarded a knight- scores that are sufficiently robust before designing hood, and people around the world know of his work. further studies that can rigorously test gene–environ- Even my dad (not involved in the field) suggested that ment interaction. In contrast to psychiatry, this type I familiarize myself with Rutter’s seminal work before of research has flourished in other fields – such as attending an interview for an undergraduate course those with clearly defined phenotypes including obe- in Psychology back in the 1990s. It was therefore an sity. Indeed, a recent GWAS meta-analysis demon- immense (and altogether terrifying) privilege to find strated an interaction between a risk locus in the FTO myself, just a few years on, working toward a PhD at gene and physical activity for body mass index (Graff the Social, Genetic, Developmental, Psychiatry Cen- et al., 2017). It has also been recently reported that tre, King’s College, London – an institution founded genetic influences had a much larger influence on by Rutter. He was at the time working on the hottest educational attainment in the post-Soviet era (when

© 2019 Association for Child and Adolescent Mental Health virtual issue 3 opportunities to thrive were more equal) as compared They also included questions about causal inference to the Soviet years (Rimfeld et al., 2018)). and the crucial observation that the mode of risk As we push forward understanding of polygenic risk mediation could differ from the origins of the risk. scores for psychiatric traits, we need to keep interplay Rutter and colleagues noted, for example, that just with the environment at the forefront of our minds, because genetic factors influence the likelihood that a lest we rewind to a time when genes were pitched person will start smoking does not necessarily mean against the environment leading to concerning that the effects of cigarette smoke on a person’s health misunderstandings. Thank you to Professor Rutter are genetically mediated. Finally, Rutter and col- and his colleagues for the inspiration. For anyone leagues reminded readers that measurement matters keen to enter the field, I’ll echo my dad’s advice: you – that whether we believe disorders are best repre- won’t go far wrong if you start by familiarizing yourself sented as categories or continua has implications for with these immense contributions. our models and that measurement error can lead to inaccurate conclusions about etiological factors. In an early statement of what would become conventional wisdom, Rutter and colleagues warned readers Papers 2 and 3: Genetics and child psychiatry: against using language that could be interpreted as Part I: Advances in quantitative and molecular genetic determinism and noted that statements about genetics and Part II: Empirical research findings ‘genes for’ a given disorder would probably misrepre- – Rutter et al. (1999a, 1999b) sent the very small amounts of variance that any gene Commentator – Sara Jaffee, University of or set of genes were likely to explain. Pennsylvania, USA Today, researchers have a vastly greater set of In 1999, I turned up at the newly established Social, quantitative and molecular genetic tools from which Genetic, and Developmental Psychiatry Centre at the to choose than the ones described in the 1999 Institute of Psychiatry in South London. Like many papers. In the GWAS era, we can genotype millions others at the SGDP Centre in those early days, I was of SNPs across the genome. Indeed, it is now looking for a roadmap. We developmental, clinical, possible and relatively affordable to sequence a and social psychologists were well-versed in life person’s entire genome. These represent technolog- course and biosocial theories of human develop- ical leaps, but the questions about how gene–envi- ment. We were already convinced that genes and ronment interplay unfolds across development that environments mattered for the development of com- Rutter and his colleagues posed in 1999 remain as plex traits, but we knew we needed different data relevant today as they were nearly 20 years ago. For than we had been collecting so far to demonstrate many of us, they continue to guide the questions we gene–environment interplay in all its complexity. We ask and shape our understanding of what our were hungry for a guide that would help us imple- findings mean. ment such a program of research. The pair of papers I have selected (Rutter et al., 1999a, 1999b) provided just such a guide. These papers gave an introduction Paper 4: Continuities and discontinuities in to readers who wanted to learn about the logic of psychopathology between childhood and twin and adoption designs and about how linkage adult life – Rutter, Kim-Cohen and Maughan studies worked. The authors were transparent about (2006) what different designs assumed and under what Commentator – Paul Ramchandani, University of circumstances those assumptions were realistic. The Cambridge, UK empirical papers presented in the companion piece brought the designs to life, offered concrete examples The first child and adolescent psychiatry conference I of how researchers navigated the constraints and attended was also the occasion of Professor Sir limitations of behavioral genetic models, and intro- Michael Rutter’s retirement Feschrift, in the late duced readers to researchers who were already 1990s. So, our working careers in the field didn’t active in the field and might provide guidance to formally coincide but, as most readers of the JCPP will newcomers looking for collaborators. know, Professor Rutter’s research output and contri- Whereas I knew at the time that I needed an bution didn’t stop there; indeed, it continues to this introduction to research designs that could answer day. The paper I have selected (Rutter, Kim-Cohen & questions I wanted to ask, I did not appreciate how Maughan, 2006) engaged my interest at the time and much I would value Rutter et al.’s efforts to integrate has been an influential review ever since. It was behavioral genetics within existing clinical, epidemi- published in 2006, close to the time when the first ological, and developmental frameworks. Reading substantial longitudinal evidence of continuities of those papers now, it is striking how many of the issues psychopathology from childhood into adulthood was Rutter and his colleagues highlighted are still central emerging in work from the Dunedin cohort study in to the field. These included an emphasis on develop- New Zealand (Kim-Cohen et al., 2003). That paper ment, noting that the relative importance of genetic was the first source I can recall of the statistic that and environmental effects could change over time. 75% of adult mental health problem had their roots

© 2019 Association for Child and Adolescent Mental Health 4 virtual issue before the age of 18 years – now a well-known and Marceau, 2008). Even if researchers are not inter- widely used policy-influencing piece of information. ested in differences between boys and girls with I’ve selected this particular review article as it regard to the associations under study per se, influenced my work, and because it addresses an including sex as a potential covariate is the rule important topic in a thorough and interesting way. It rather than the exception, and sex differences are also illustrates a number of key points about the work often tested almost mechanically. This habit has and influence of Professor Rutter, five of which I will prevented spurious association due to confounding briefly address here: First, the article has scale and by sex and yielded lots of suggested sex-specific ambition. It moves beyond research findings to really associations. However, it has not necessarily pro- interrogate potential mechanisms. It is also not moted sex differences as a tool to learn more about focussed on a single disorder, instead covering a the etiology of mental health problems (Oldehinkel, broad range of psychiatric and developmental condi- 2017). Despite the fact that is was published fifteen tions, to illustrate similarities and differences across years ago, Rutter, Caspi, and Moffitt’s review on sex different presentations. Second, the review illustrates differences is still a shining example of how investi- the scale and scope of research in Child and Adoles- gation of mechanisms underlying empirical sex dif- cent Psychiatry at the Institute of Psychiatry in ferences can actually be used to derive hypotheses London (now the IoPPN), including the work of Kim- about the etiology of psychiatric disorders. In their Cohen and colleagues cited above. It was at this time, study, they focused particularly on one of the most and arguably remains, the leading research institute robust findings with regard to sex differences in in developmental mental health in the world. Profes- psychopathology: Boys are overrepresented in early- sor Rutter was instrumental in developing and leading onset neurodevelopmental disorders such as autism it for many years. Third, it also illustrates collabora- spectrum disorders and ADHD, and girls in adoles- tion, and in particular collaboration with other lead- cent-onset emotional disorders such as depression ing researchers, such as Professor Barbara Maughan, and social anxiety. Considering the cross-diagnostic whose huge contribution to developmental epidemi- nature of these differences, Rutter and colleagues ology does not always get the full recognition it so discussed the possibility of a unifying explanation clearly deserves. Fourth, this work was at the cutting for the similarities and reviewed the literature to find edge of developmental science at the time. High- leads for that. But actually they did much more than quality longitudinal research on developmental con- that; the article can be read as a manual of how to set tinuities into adult life was really just emerging. up a smart and systematic research strategy with Although many in the field of child and adolescent regard to any topic. This paper, which has been cited mental health would have confidently asserted that over 500 times, has inspired many researchers in the the origins of many ‘adult’ mental health problems field of developmental psychopathology, among emerged in childhood and adolescence, it took high- whom I count myself. It is extremely comprehensive quality research evidence of this kind to convince and provides more food for thought than many those working with adults, and subsequently to textbooks. It contains instructive overviews of the influence policy in a substantive way. Fifth and methodological hurdles in conducting research on finally, this paper serves as a reminder that the causes of sex differences in psychopathology, and developmental perspective on mental health prob- strategies to do so effectively. Moreover, it offers a lems in only relatively established, and has only even theoretical framework to study sex differences by more recently gone mainstream. distinguishing between genetic differences, differ- Like many of Professor Rutter’s more detailed ences in the biological and social consequences of reviews, reading this paper requires dedicated con- being male or female, and differences in risk or centration and, for me at least, several visits to protective factors that are more directly implicated in absorb its messages. The rewards of reading this the causal psychopathological mechanisms. This paper are great – many of the challenges it raises, distinction, and the suggestion that ‘Rather than including the strong advocacy of testing competing searching for interactions between sex and risk hypotheses on mediating processes, remain very factors, as is usually done, it may be more profitable pertinent 12 years later. to examine whether more proximal sex-linked char- acteristics create vulnerabilities to specific risks’ (p. 1104), has helped tremendously to structure the massive pile of reports on sex differences in psy- Paper 5: Using sex differences in chopathology and steer the interpretation of these psychopathology to study causal mechanisms: findings. The recommendations provided by Rutter unifying issues and research strategies – Rutter and colleagues in this article are still valid and up to et al. (2003) date. They concluded by stating that ‘The research Commentator 1 – A.J. Oldehinkel, University of challenges are considerable but the potential Groningen, The Netherlands rewards are great because of the light likely to be Sex differences feature in many child psychology and shed on some of the key causal processes involved in psychiatry studies (Zahn-Waxler, Shirtcliff, & the etiology of mental disorders’ (p. 1109). I think

© 2019 Association for Child and Adolescent Mental Health virtual issue 5 this is as true now as it was sixteen years ago, in the disorder in both sexes. Some funding agencies 2003. (e.g., the National Institutes of Health in the United States) have identified the paucity of research in this area and are currently addressing these gaps by Commentator 2 – Kelly Klump, Michigan State establishing strict criteria for inclusion of males and University, USA females in all types of research (see Clayton & I remember reading this article by Drs. Rutter, Collins, 2014), and a focus on understanding sex Caspi, and Moffitt in 2003 and feeling a renewed differences in risk at all levels of analysis (see Pinn, sense of clarity regarding my own research program. Clayton, Begg, & Sass, 2010). This focus is much I was a junior scientist studying the role of ovarian needed and is the type of research agenda Rutter hormones in increasing risk for eating disorders in et al. (2003) called for over 20 years ago. In addition females and for contributing to sex differences in to honoring Dr. Rutter, it is my hope that this risk. At the time, sex differences were a less com- commentary and special issue will remind us of monly studied phenomenon, and the playing field Rutter et al.’s (2003) seminal paper and the road seemed vast in terms of the number of influences map it provided for understanding sex differences in that could contribute to risk, confound hormone risk for psychopathology. Otherwise, we are at risk of influences, and/or cause the very hormone influ- repeating our methodological mistakes of the past ences I was studying. Rutter et al.’s (2003) paper and generating new data that fail to answer the key provided clarity on these issues in a way that no question – namely, how do distal and proximal risk paper had done before. The article carefully laid out factors account for sex differences in risk and the evidence in support for sex differences in some, contribute to the etiology of major forms of psy- but not all, disorders, including eating disorders. It chopathology? then described a cogent and clear model for how to think about these sex differences and begin studying causal influences starting with distal factors that are Paper 6: Institutional care: risk from family more fixed (e.g., genetic influences), then moving to a background or pattern of rearing – Roy et al. variety of factors that are the consequences of being (2000) male or female, and then to the proximal risk and Commentator – Megan R. Gunnar, University of protective factors. This framework provided a critical Minnesota, USA starting point for thinking about entry into the field and the optimal progression of research inquiry. The Nature, Nurture, & Rutter. In 1989, the communist paper went on to describe the methodological limi- regime in Romania fell. Shortly after that the world tations of many contemporary approaches to study- became aware of the numerous infants and children ing sex differences, including the tendency to only who were being reared in institutions and who were study one sex, or to only examine risk factors within then available for adoption. Many of those children sex, or to examine both sexes, but not test the critical were adopted into Great Britain and not long after sex x risk factor interaction that is needed to that, the government asked Michael Rutter to eval- establish sex differences. I was humbled by this uate how they were fairing. Professor Rutter was the explication of the substantial limitations of past logical choice because, among his many other areas studies, as I had perpetrated some of these method- of expertise, he was an expert on the impact of ological no-no’s in my own work. One of the most institutionalization on children. What became critical points made was the need to show that the known as the English and Romanian Adoption Study risk factor must reduce or eliminate sex differences revealed the sequelae of what Rutter termed, ‘pro- in risk. The putative risk factor (regardless of its found institutional deprivation’. The children, he status as a distal risk factor, proximal risk factor, found, were at risk for ‘deprivation specific effects’, a etc.) must partially or wholly account for the pre- constellation of low IQ, inattention-overactivity, dis- dominance of the disorder in one sex over the other. inhibited attachment disorder, and quasi-autism. As Rutter et al. pointed out in 2003, very few studies Notable among this constellation were problems of included this critical test in establishing that a risk attention regulation/hyperactivity and what at the factor was causal in sex differences for psy- time was interpreted as a failure to form specific chopathology. Unfortunately, to this day, many attachments. Both of these problems were common studies still fail to conduct this important and in the literature associated with poor and unstable necessary test in the evidentiary pathway. early caregiving environments. But children do not As I write this commentary, I am struck by the fact end up in such environments by chance. Typically, that we still have very few studies of sex differences they come from families that are disorganized, in psychopathology. Rutter et al. (2003) made a chaotic, and often maltreating. As Rutter knew, compelling case that understanding sex differences experiments of nature rarely do a good job of will open a window to novel neurobiological, psy- separating nature and nurture, not that they operate chosocial, and psychological factors that likely con- separately anyway. Nonetheless, if for nothing more tribute in highly substantive ways to the etiology of than reasons of policy, it was critical to be able to test

© 2019 Association for Child and Adolescent Mental Health 6 virtual issue whether children who experience institutional care model for the use of longitudinal studies in the would have had these difficulties regardless of their future of mental health research. rearing histories. The article we have selected (Rutter et al., 2007) is In the early 2000s, Professor Rutter, along with one of three installments by Dr. Rutter and col- Penny Roy and Andrew Pickles, published two leagues examining outcomes at 11 years of age. It studies using a carefully constructed sample of explores the developmental significance of autistic- school-aged children ages 5 through 8 years. One like traits in relation to cognition and extent of group of 19 were identified from national social deprivation. Their conclusions expand our under- service records to have been in institutional care standing of the autism spectrum and more atypical continuously beginning in infancy (average age @ 3 presentations, as well as the role that socialization months). A second group of 19 were matched to plays in social cognition development. Longitudinal these children by age, sex, and race/ethnicity, but studies are often limited by heterogeneity and con- were in foster care continuously from infancy. There founding factors, but the investigators skilfully was a comparison group of children of the same sex studied the life trajectory of Romanian adoptees in and age drawn from each child’s classroom, but England to isolate one variable: duration of depriva- who had never been in out-of-home care. In the first tion. ‘Seeing the forest for the trees’ is one of the main analysis, published in 2000 (Roy et al., 2000), the lessons of this large-scale longitudinal study. Each results clearly showed that inattention/hyperactiv- child in the study followed a unique and seemingly ity was greater in the institutionalized group, while random trajectory leading to a distinct clinical pre- after controlling for several covariates, the foster sentation. Nevertheless, in a group analysis, the care and control groups did not differ. This was investigators modeled how a psychiatric epidemiol- despite the family backgrounds for both the insti- ogy perspective can advance our understanding of tutionalized and foster care groups being strikingly causal pathways. It did not suffice to echo the poor. In the second analysis, published in 2004 common belief that an environmental factor con- (Roy, Rutter, & Pickles, 2004), the trio provided tributed to psychopathology (Rutter, 2005). Rather evidence of significant overlap between disinhibited the investigators described evidence that links a attachment disordered behavior (what would later particular stressor (profound deprivation) with a be termed disorders of social engagement) and specific psychopathologic effect. They found that inattention/overactivity. This result presaged find- individuals with more than 6 months of institutional ings from the ERA study and from other studies of rearing in infancy were at significantly higher risk of postinstitutionalized children, including my own displaying social disinhibition, inattention, and over- (Tarullo, Garvin, & Gunnar, 2011). While we might activity. bemoan the small sample size of the Roy, Rutter, In a recent interview, Dr. Rutter described his and Pickles’ study, the intricate sampling that work with the English and Romanian adoptees as controlled for many factors that are not typically ‘one of the more interesting bits of work [he has] done controllable, even in genetically informed designs, since it was so full of surprises’. When Romanian was a very creative way to address a very thorny children were studied years after adoption, those problem in developmental science. Reading these with extended global deprivation presented social two papers certainly was inspirational for me and communication deficits and obsessive behaviors, a my students. profile labeled ‘quasi-autism phenotype’ (Rutter et al., 1999). The investigators had not included assessments for autistic patterns in the original protocol, as this aspect of early deprivation in Paper 7: Early adolescent outcomes of adoptees had not been described in the literature institutionally deprived and non-deprived before. The quasi-autism phenotype was initially adoptees III. Quasi-autism – Rutter et al. (2007) described as severe but remitting. The early adoles- Commentators – Andrea Diaz-Stransky & Michael H. cence follow-up suggested that while the autistic-like Bloch, Yale University, USA traits were persistent, some of them showed One of Dr. Michael Rutter’s master pieces of scien- improvement. Nevertheless, a subsequent young tific research is the Romanian Adoptees study. It adult follow-up study revealed yet another surprise consists of a large-scale longitudinal cohort study of (Sonuga-Barke et al., 2017). The investigators found Romanian orphans who were institutionalized and that such phenotype was all but remitting. Thus, the profoundly deprived in infancy and given up for investigators revised their understanding of this adoption to families in England. The children were domain. Through instances like this, Prof. Rutter followed at various time-points to trace their devel- also has also exemplified the maxim to ‘let the data opmental trajectories following adoption and were tell the story’. compared to a group of adoptees born in the United Early in training, pediatricians learn to assess a Kingdom and adopted prior to age 6 months (Rutter, child’s growth based on several time-points, tracing 1998; Sonuga-Barke et al., 2017). The English and a growth curve. In a similar way, studying child Romanian adoptees study serves as a paramount development requires longitudinal studies that

© 2019 Association for Child and Adolescent Mental Health virtual issue 7 include assessments from multiple time-points. Interestingly, intellectual disability and epilepsy Without a longitudinal study, we would not be able propensity were not part of the BAP suggesting that to surmise the different effects that one stressor both features often associated with autism may not (institutional deprivation) can have on different be genetically influenced. This initial twin study also domains such as social, emotional, and cognitive raised questions about an additional etiological role trajectories. While disinhibited social engagement of obstetric complications in autism risk, an hypoth- persisted from childhood through early adulthood, esis that was later refuted when additional twin pairs emotional problems were latent and surfaced in the were recruited for a larger twin study. adolescent–adulthood transition years. This con- trasted with remission of cognitive impairment. Such normalization of cognitive impairment provides a Paper 9: Quasi-autistic patterns following remarkable example of neuroplasticity beyond early severe early global privation – Rutter et al. childhood. This evidence of neuroplasticity is invalu- (1999) able for those studying the biologic underpinnings of Commentator – Jonathan Green, University of developmental psychopathology. A final lesson can Manchester, UK be learned from Dr. Rutter’s clinical work following retirement, as he has continued to care for Roma- Mike Rutter et al.’s 1999 ‘Quasi-Autism’ paper nian adoptees. We learn from one of the Fathers of caused an immediate stir and was quickly recog- Child Psychiatry that above all, we must always nized as a landmark publication. It had high uphold our duty to our patients. significance for me personally; my own research work in the 1990s had spanned across autism (the UK Asperger syndrome study with Tony Cox, and in the International Molecular Genetic Study of Autism Paper 8: Infantile autism: a genetic study of 21 Consortium under Mike’s leadership), and early twin pairs – Folstein & Rutter (1977) relationship and attachment studies (including Commentator – Eric Fombonne, Oregon State developing the Manchester Child Attachment Story University, USA Task) – united by an interest in the determinants of In the 1960s, the possibility of genetic influences on early social development and its disorders. Clini- autism was generally dismissed based on several cally, from the mid-1990s, I saw a succession of (later shown to be fallacious) arguments: (a) No families with children adopted from early familial vertical transmission of autism was observed (chil- neglect and maltreatment, whom I thought showed dren with autism never had a parent with autism); autistic social impairments rather than the (b) The (very crude) cytogenetic techniques rarely assumed social difficulties consequent on early found chromosomal abnormalities; and (c) Sibling trauma or avoidance of intimacy and relating. recurrence was extremely low, around 2%. Recogni- Reframing the formulation in neurodevelopmental tion that the sibling risk, when compared to the 2–4/ terms at that time seemed daring and without 10,000 population base rate of the time, showed a theoretical context – but important as leading to 50- to 100-fold increase in disease risk, prompted substantive recalibration of appropriate treatment, this first twin study. Based on a small sample of 11 and seemingly intuitively helpful to parents. In this MZ and 10 DZ pairs, the concordance rates were context, for me, the ‘quasi-autism’ paper was reve- markedly different for MZ (4 out of 11; 36%) and DZ latory. My first thought on hearing about it was how (0 out of 10; 0%) pairs. Moreover, this study showed brave it was: for the person who had done more that what was inherited was not only severe autism than anyone to move thinking about autism away but a liability to a broader set of developmental from theories of early environmental etiology to abnormalities involving social and communication publish a case series of autism-like phenomenology development alongside atypical patterns of interests, after early social privation, was in a way breathtak- later to be known as the ‘broader autism phenotype’ ing. I found the findings clinically confirmatory and (BAP). Like narrowly defined autism, concordance academically inspiring. for the BAP was much higher in MZ vs DZ pairs (82% The paper itself is a comparative descriptive vs. 10%) indicating strong genetic influence on the account from the English Romanian Adoptees BAP. These findings translated into heritability esti- (ERA) study; comprising a core group of 111 children mates above 90%, making autism one of the most seen longitudinally at 4 and 6 years, and additional heritable disorder studied by psychiatrists. Follow- data from the full 165 ERA children seen only at up studies of unaffected MZ co-twins further vali- 6 years; compared with the ERA cohort of 53 dated the BAP in showing that social deficits could adopted children from UK background and indepen- emerge during adolescent development when devel- dent data from a longitudinal study of typical opmental pressures on social behavior increase with autism. Structured histories with ADI are compli- age and maturation. The BAP was also validated in mented with research observations and Mike’s own family studies where siblings unaffected with autism clinical assessments of the likely autism children. were shown to have a raised risk of the BAP. The findings are well known; a subgroup of N = 3/111

© 2019 Association for Child and Adolescent Mental Health 8 virtual issue with a picture of accepted autism with likely organic a paradigm shift in how autism was seen that was, cause linked to relative mental retardation, small by the 1990s, essentially complete. Now here were head circumference, and in one, severe malnutrition observations that must have seemed potentially to and prematurity; a subgroup of N = 7, about 6% of challenge this account – at the very least Mike will the whole, with a ‘quasi-autism pattern’ – described have acutely known that their publication would be as such because of somewhat atypical phenomenol- seized on by continuing proponents of environmen- ogy, an unusual course of reducing severity between tal theories. In the history of scientific enquiry and 4 and 6 years and lack of organic stigmata; and a intellectual progress, the most common response to further N = 10/165 who showing some parent-re- inconvenient facts of this kind has been to deny or ported autism features on ASQ (now renamed the suppress them. Mike notes at the beginning of the SCQ). The paper concluded that the prevalence of paper how the initial ERA design coincided with two these autism features was well above the chance clinical referrals of possible autism from Romanian given that the then-understood population preva- adoptees. It may seem inevitable in retrospect that lence and that the origin of the quasi-autism pattern he consequently took the decision to design in some were very unlikely to be organic (including malnour- autism assessments into ERA; however, life is lived ishment), but rather a developmental response to forwards and is full of branch points (as his own extreme social privation or a lack of early perceptual research has shown); the counterfactual would have input. However, there was no evidence of a contin- been to dismiss the referrals as coincidence and uum of ASD like impairments of lesser severity designing in autism assessment as not at all throughout the cohort. relevant given theory at the time, or at least as too Rereading the paper 20 years after its publica- ‘politically’ inconvenient or sensitive to bother with. tion, the first thing to say is what a beautifully The fact that he did decide to test the possibility of written and thorough description it is, in some ways autism in ERA, in a sense potentially challenging squarely in the tradition of descriptive phenomenol- the paradigm he himself had played a major part in ogy going back to Jaspers and before. Twenty-six developing, speaks volumes to his essential com- children (including the 11 possible ASD children mitment to scientific method and values, to go studied for the paper) were seen for detailed clinical where observations and the data took him (a rarer assessment by Mike himself – illustrating the extent quality than commonly supposed in this or any of his commitment to personal direct clinical obser- time). vation within a scientific study. When I came to lead In the event, the decision to address ‘inconvenient a somewhat analogous study some years later (as truths’ in this paper was highly productive, and below), I undertook (modeled on this paper) to opened up another paradigm shift toward a more repeat this on my sample – and can attest to the sophisticated GxE interplay within the developmen- clinical effort involved while also leading the tal neuroscience of autism. This story is still being science. This classic phenomenological description written, not least in the further longitudinal follow- is however taken on several stages within a longi- up studies of the ERA cohort, but this 1999 paper tudinal quasi-experimental design, using a compar- provided a truly radical pivot. Inspired by it, I and my ative approach to elicit patterns and allow team replicated the same approach in UK children in preliminary causal inferences – this without losing adoptive care after early within-family neglect and the richness of the clinical material (somewhat maltreatment. We came up with remarkably similar nostalgic reading this, since many contemporary findings on autism at age 7 years (Green, Leadbitter, observational designs, alongside Journal space Kay, & Sharma, 2016). Our assessments, a decade restrictions, have squeezed out much such clinical and more after the ERA 6 year work, used ADOS as richness in reports). One has the impression that well as evolved CPEA/DSM5 criteria – and within Mike was well aware of the historical importance of that our cases rather similar to the quasi-autism the observations he was making, taking great care descriptions all met criteria for ASD; raising the with the case reporting not to over-systematize a intriguing possibility that reanalysis of the ERA data complex clinical picture, and only making tentative by current definitions might also conclude the same causal inferences. (at least on phenomenology – the developmental Finally, I have always felt that this paper repre- trajectory remains distinctive). Further work has sents, more than perhaps any other, the quality of extended the descriptive and longitudinal work of Mike’s scientific attitude. The presentation is ASD and what is now called Disinhibited Social scrupulously empirical, with no effort to impose a Engagement Disorder (DSED) and related social prior theory position. It has to be read as suggested impairments after early social, perceptual, and above in the context of the battles that Mike had led emotional adversity, opening up a field of enquiry along with others over the previous decades to into the neurodevelopmental (rather than just psy- reframe autism as a highly heritable neurodevelop- chological) consequence of early privation that has mental disorder, against a powerful previous envi- deep theoretical and clinical implications. All that ronmental causation paradigm from psychoanalysis work really has its origin in Mike’s seminal 1999 and others. This arduous empirical work had led to paper.

far’ results indicate that specific reading retardation Paper 10: The concept of specific reading picks out a statistically distinctive group of poor retardation – Rutter and Yule (1975) readers and has important clinical and educational Commentator – Jeffrey M. Halperin, Queens implications. Yet, as indicated by their use of the College, City University of New York, NY, USA phrase ‘so far’, they implicitly acknowledge that This classic paper by Michael Rutter and William Yule science is a journey made up of small steps, and call (1975), which had a substantial impact on my early for replication of findings. Importantly, as no data career and conceptualizations regarding childhood were available at the time, they call for investigation reading disabilities, represents to me a model for how into whether the two groups require differential scientific inquiry should be pursued. It demonstrates remediation. clarity of thinking, a logical sequence of steps for The research described in this paper set the stage addressing a problem, and a conservative discussion for a substantial body of later research, much of ofthefindingsthatexplicitlystateswhatwas,andwhat which has focused on measurement of (and prob- was not, known at the time. It had a clarity of writing lems with) IQ-based definitions of reading disorders, thatgivesitthefeelofaone-sideddiscussionorlecture. the development of more optimal approaches to With more than four decades of progress since the diagnosis, and how best to treat reading difficulties. publication of this paper, some may quibble or even We still have a long way to go before we fully disagree with some of the authors’ conclusions. Still understand this etiologically and phenomenologi- today though, the approach to scientific thinking is cally heterogeneous disorder, but needless to say, impeccable. this classic paper played a key role in moving the The paper focuses on the ‘nature of reading prob- field forward long before we had the tools to elucidate lems’, and most notably, on the distinction between underlying biological mechanisms. what the authors refer to as ‘general reading backwardness’ and ‘specific reading retardation’. General reading backwardness describes children who are Paper 11: Children in lesbian and single-parent poor readers relative to their age, irrespective of households: psychosexual and psychiatric intelligence. Those with specific reading retardation appraisal – Golombok et al. (1983) are impaired in reading relative to both their age and Commentators: Nicole Sitkin Zelin and Michael H. Bloch IQ. Those with general reading backwardness, as a (Stanford University & Yale Medical School), USA group, have lower IQ scores, but as Rutter and Yule point out, this difference is by definition and thus We would like to bring attention to one of Sir Michael provides no information of particular interest or Rutter’s less famous contributions to JCPP, which clinical utility. They rightly insist that to infer a valid nonetheless was brave, important and roughly distinction between them, the groups must differ on 25 years ahead of its time. Scientific research is other measures. After a scholarly and compelling influenced by, and responds to, the sociocultural discussion of the broad concept of underachievement context in which it occurs. Scientific consensus can and a range of measurement issues, they then exam- thus guide or evaluate policies and laws in ways that ine data from five epidemiological samples with a profoundly impact the lives, wellbeing, and health of focus on indices of etiology and prognosis. Regret- communities. Empirical research on sexual minority tably, the authors point out, no data on treatment families developed in the 1970s–80s in response to response were available at the time. Rutter and Yule custody disputes between sexual minority parents initially demonstrate a ‘hump’ in the lower, but not the and their former heterosexual partners. In contrast upper, end of the distribution of reading scores, to the standard practice of awarding custody to the supporting the notion that specific reading retarda- mother after divorce, lesbian women were often tion is not merely the tail end of a Gaussian distribu- denied custody based on the presumption that tion. Then, they show that reading retardation differs children would suffer if raised in nontraditional significantly from reading backwardness in sex ratio, households (Golombok, 2017). It was contended rates of neurological disorder, pattern of neurodevel- that children raised in such households would suffer opmental deficits, and educational course/prognosis. atypical sexual orientation development, poor peer Those with general reading backwardness had a relationships, and elevated rates of emotional and broad range of neural and neurodevelopmental behavioral problems. In 1983, Dr. Michael Rutter anomalies, but children with specific reading retar- and colleagues published an empirical challenge to dation had relatively selective deficits in speech and these arguments (Golombok et al., 1983). In tackling language development. Further, despite their higher such a controversial topic, he risked his professional I.Qs, the children with specific reading retardation reputation. However, by doing so he has helped to made significantly less progress in reading over a 4- to lay the foundations for what has become a robust 5-year follow-up period compared to children with body of evidence showing no difference in develop- general reading backwardness, but made more pro- mental outcomes between the children of sexual gress in arithmetic. Rutter and Yule concluded that ‘so minority and heterosexual parents.

Rutter’s team compared outcomes for children London, London, and 4The Anna Freud National raised in households headed by a single, divorced Centre for Children and Families, London, UK heterosexual mother to those raised in a household headed by one or two lesbian mothers. This approach controlled for the impact of familial dis- References (editors’ selections in bold) ruption and discord on child development and Clayton, J.A., & Collins, F. (2014). Policy: NIH to balance sex in – behavior. No difference in gender or sexual orienta- cell and animal studies. Nature, 509, 282 283. Farr, R.H., & Patterson, C.J. (2013). Co-parenting among tion development was found in these groups – a lesbian, gay, and heterosexual couples: Associations with finding subsequently supported by longitudinal and adopted children’s outcomes. Child Development, 84, 1226– population-based analyses and analyses with differ- 1240. ent types of sexual minority households (Greenfeld, Folstein, S., & Rutter, M. (1977). Infantile autism: A 2005). Furthermore, no differences in the duration genetic study of 21 twin pairs. Journal of Child Psychol- ogy and Psychiatry, 18, 297–321. or quality of peer relationships enjoyed by the Golombok, S. (2017). Parenting in new family forms. Current children of lesbian households were found. Subse- Opinion in Psychology, 15,76–80. quent research has also confirmed that children of Golombok, S., Spencer, A., & Rutter, M. (1983). Children in sexual minority families experience no differences in lesbian and single-parent households: Psychosexual and peer relationships or victimization (Telingator & psychiatric appraisal. Journal of Child Psychology and Psychiatry, 24, 551–572. Patterson, 2008) although some children raised in Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., sexual minority families report bullying or teasing Barata, L., ... & Kilpelainen,€ T.O. (2017). Genome-wide related to their family structure or their own sexual physical activity interactions in adiposity. A meta-analysis of orientation (Webster & Telingator, 2016). Lastly, the 200,452 adults. Plos Genetics, 13, e1006528. authors found no link between rates of emotional or Green, J., Leadbitter, K., Kay, C., & Sharma, K. (2016). Autism spectrum disorder in children adopted after early care behavioral problems in lesbian households. Instead, breakdown. Journal of Autism and Developmental Disorders, children in households headed by single, heterosex- 46, 1392–1402. ual mothers displayed more emotional and behav- Greenfeld, D.A. (2005). Reproduction in same sex couples: ioral difficulties and use of mental health services. Quality of parenting and child development. Current Opinion – Again, this finding has been born out by subsequent Obstetric Gynecolology, 17, 309 312. Jansen, P.R., Watanabe, K., Stringer, S., Skene, N., Bryois, J., research showing no effect of growing up in lesbian Hammerschlag, A.R., ... & Posthuma, D. (2018). Genome- and same-gender families on a range of cognitive, wide analysis of insomnia (N=1,331,010) identifies novel loci behavioral, and mental health outcome (Lavner, and functional pathways. bioRxiv, 214973. Waterman, & Peplau, 2012; Reczek, Spiker, Liu, & Kim-Cohen, J., Caspi, A., Moffitt, T.E., Harrington, H., Milne, Crosnoe, 2017). The quality of relationships within B.J., & Poulton, R. (2003). Prior juvenile diagnoses in adults with mental disorder: Developmental follow-back of a the family, not the composition of the family, seemed prospective-longitudinal cohort. Archives of General Psychi- to be most important in predicting outcomes in these atry, 60, 709–717. studies (Farr & Patterson, 2013). Some studies have Lavner, J.A., Waterman, J., & Peplau, L.A. (2012). Can gay and suggested that children raised in a nontraditional lesbian parents promote healthy development in high-risk families are more nurturing and accepting have children adopted from foster care? American Journal of Orthopsychiatry, 82, 465–472. higher social and academic competence and display Oldehinkel, A.J. (2017). Editorial: Let’s talk about sex – The fewer behavioral problems (Riggs & Due, 2014). gender binary revisited. Journal of Child Psychology and Despite this evidence, structural barriers continue Psychiatry, 58, 863–864. to hinder sexual minority couples from forming Pinn, V.W., Clayton, J.A., Begg, L., & Sass, S.E. (2010). Public families in many countries and many prospective partnerships for a vision for women’s health research in 2020. Journal of Women’s Health, 19(9), 1603–1607. parents encounter prejudice while attempting to Reczek, C., Spiker, R., Liu, H., & Crosnoe, R. (2017). The build families through foster care and adoption. promise and perils of population research on same-sex The continuation and expansion of Golombok et al.’s families. Demography, 54, 2385–2397. (1983) research will critically inform the ongoing Riggs, D.W., & Due, C. (2014). Gay fathers’ reproductive evolution of law, policy, and public opinion. Sir journeys and parenting experiences: A review of research. Journal of Family Planning and Reproductive Health Care, Michael Rutter has made a major contribution to 40, 289–293. scientifically informing public discourse on an issue Rimfeld, K., Krapohl, E., Trzaskowski, M., Coleman, J.R.I., with tremendous importance to many children and Selzam, S., Dale, P.S., ... & Plomin, R. (2018). Genetic their families. influence on social outcomes during and after the Soviet era in Estonia. Nature Human Behaviour, 2, 269–275. Roy, P., Rutter, M., & Pickles, A. (2000). Institutional care: 1,2 Risk from family background or pattern of rearing? Jour- Edmund Sonuga-Barke – 3,4 nal of Child Psychology and Psychiatry, 41, 139 149. Pasco Fearon Roy, P., Rutter, M., & Pickles, A. (2004). Institutional care: 1 Institute of Psychiatry, Psychology & Neuroscience, Associations between overactivity and lack of selectivity in King’s College London, London, UK; 2Department of social relationships. Journal of Child Psychology & Psychi- Child & Adolescent Psychiatry, Aarhus University, atry, 45, 866–873. Aarhus, Denmark; 3Research Department of Clinical, Rutter, M. (1998). Developmental catch-up, and deficit, following adoption after severe global early privation. English Educational & Health Psychology, University College

and Romanian Adoptees (ERA) Study Team. Journal of Child quantitative and molecular genetics. Journal of Child Psychology & Psychiatry, 39, 465–476. Psychology and Psychiatry, 40,3–18. Rutter, M. (2005). Environmentally mediated risks for psy- Rutter, M., Silberg, J., O’Connor, T., & Siminoff, E. chopathology: Research strategies and findings. Journal of (1999b). Genetics and child psychiatry: II. Empirical the American Academy of Child & Adolescent Psychiatry, 44, research findings. Journal of Child Psychology and 3–18. Psychiatry, 40,19–55. Rutter, M., Andersen-Wood, L., Beckett, C., Bredenkamp, Rutter, M., & Yule, W. (1975). The concept of specific D., Castle, J., Groothues, C., ... & O’Connor, T.G. (1999). reading retardation. Journal of Child Psychology and Quasi-autistic patterns following severe early global Psychiatry, 16, 181–197. privation. English and Romanian Adoptees (ERA) Study Sonuga-Barke, E.J.S., Kennedy, M., Kumsta, R., Knights, N., Team. Journal of Child Psychology and Psychiatry, 40, Golm, D., Rutter, M., Maughan, B., Schlotz, W., & Kreppner, 537–549. J. (2017). Child-to-adult neurodevelopmental and mental Rutter, M., Caspi, A., & Moffitt, T.E. (2003). Using sex health trajectories after early life deprivation: The young differences in psychopathology to study causal mecha- adult follow-up of the longitudinal English and Romanian nisms: Unifying issues and research strategies. Journal Adoptees study. Lancet, 389, 1539–1548. of Child Psychology and Psychiatry, 44, 1092–1115. Tarullo, A.R., Garvin, M.C., & Gunnar, M.R. (2011). Atypical Rutter, M., Kim-Cohen, J., & Maughan, B. (2006). Conti- EEG power correlates with indiscriminately friendly behav- nuities and discontinuities in psychopathology between ior in internationally adopted children. Developmental Psy- childhood and adult life. Journal of Child Psychology chology, 47, 417–431. and Psychiatry, 47, 276–295. Telingator, C.J., & Patterson, C. (2008). Children and adoles- Rutter, M., Kreppner, J., Croft, C., Murin, M., Colvert, E., cents of lesbian and gay parents. Journal of the American Beckett, C., ... & Sonuga-Barke, E. (2007). Early adoles- Academy of Child & Adolescent Psychiatry, 47, 1364–1368. cent outcomes of institutionally deprived and non- Webster, C.R., Jr, & Telingator, C.J. (2016). Lesbian, gay, deprived adoptees III. Quasi-autism. Journal of Child bisexual, and transgender families. Pediatric Clinics of North Psychology and Psychiatry, 48, 1200–1207. America, 63, 1107–1119. Rutter, M., Moffitt, T.E., & Caspi, A. (2006). Gene-environ- Zahn-Waxler, C., Shirtcliff, E.A., & Marceau, K. (2008). Disor- ment interplay and psychopathology: Multiple varieties ders of childhood and adolescence: Gender and psy- but real effects. Journal of Child Psychology and Psy- chopathology. Annual Review of Clinical Psychology, 4, chiatry, 47, 226–261. 275–303. Rutter, M., Silberg, J., O’Connor, T., & Simonoff, E. (1999a). Genetics and child psychiatry: I. Advances in