REVIEW

Longitudinal Studies Using a “NaturalExperiment” Design: The Case of Adoptees

From Romanian InstitutionsMichael Rutter, M.D., Robert Kumsta, Ph.D., Wolff Schlotz, Ph.D.,

Edmund Sonuga-Barke, Ph.D.

Objective: To summarize the advantages and limitations of general population, high-risk and“natural experiment” longitudinal studies for studying psychological change. The English andRomanian Adoptees study is used as an example of a “natural experiment,” and detailedfindings are provided. Method: What is new is a focus on the young people who spent thewhole of their life in institutional care up to the time of adoption and who did not showsubnutrition. The results were compared with a composite comparison group who had notexperienced institutional care or who were adopted before the age of 6 months. The outcomeswere assessed in terms of previously established deprivation-specific patterns (DSPs). Re-sults: “Pure” psychosocial deprivation was associated with a substantial increase in the rateof DSPs. It was not associated with significantly impaired head growth if institutional carelasted less than 6 months, whereas thereafter there was a 2.5 standard deviation reduction.Subnutrition differed in being accompanied by impaired head and body growth even withinstitutional care lasting less than 6 months. In the pure psychosocial deprivation group, 45.5%showed a DSP at 15 years compared with 1.3% in the comparison group. Conclu-sion: “Pure” psychosocial deprivation (in the absence of subnutrition) had a profound effecton psychological functioning in the form of DSPs. Subnutrition had a surprisingly small effecton DSPs. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(8):762–770. Key Words: naturalexperiment, adoptee design, “pure” psychosocial deprivation, deprivation-specific patterns,causal inference

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B aldwin,1 the father of modern developmen-tal psychology, argued that a longitudinalstudy is “an absolutely essential research

method if we are to get firm knowledge ofpsychological change, but paradoxically, itshould be avoided whenever possible.” What hemeant was that longitudinal research was expen-sive and time consuming and should be em-barked upon only when cross-sectional studieshad “cleared the ground” to delineate the keydevelopmental questions to be investigated. Theauthors agree, but they wish to emphasize that,in many cases, the crucial preliminary ground-clearing operations have already been under-taken and, therefore, well-planned longitudinal

This article will be discussed in an editorial by Drs. James J.

aHudziak and Douglas K. Novins in an upcoming issue.

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studies using high-quality data must constitute apriority.2 In this review, the authors focus onsolating developmental mechanisms linkingarly adversity to later psychopathology andhey subdivide longitudinal studies into threeifferent varieties. The first two varieties areonsidered only by their overall mix of strengthsnd weaknesses, without reviewing specifictudies in detail. The third variety, “natural ex-eriments” is considered in greater detail using

he authors’ study of Romanian adoptees as anxample.

eneral Population Sampleseneral population studies, like all prospective

ongitudinal studies, have three major advan-ages over cross-sectional studies. First, givenppropriately sensitive measurement methods

nd multiple assessment points, they allow the

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accurate timing of postulated key risk or protec-tive experiences and the time sequence of theevolution of disorders. The Dunedin Longitudi-nal Study well exemplifies this in the distinctionsbetween childhood-onset and adolescent-onsetantisocial behavior3 and in showing that retro-spective studies provide a misleading picture ofperiod prevalence compared with repeated mea-surement during the course of the longitudinalstudy.4 The findings from this and other longitu-dinal studies were decisive in showing thatschizophrenia, but not bipolar disorder, was as-sociated with neurodevelopmental impairmentsin language and motor functions in the preschoolyears5 and in showing the predictive importanceof psychotic-like features in later childhood.6

Similarly, longitudinal data were crucial in indi-cating that a large proportion of serious mentaldisorders in early adult life had been preceded byclear indications of psychopathology in child-hood.7 The second advantage of longitudinal data,provided that they tap a range of outcomes, is thatthey allow the systematic study of heterotypiccontinuities in psychopathology.8 That is, they canstudy the ways in which manifestations may varyover the course of development—as, for example,in attention-deficit/hyperactivity disorder.9 Third,the availability of data from multiple time pointsallows samples to include a very large proportionof individuals with relevant data at several timepoints, although some data may not be available atevery point.10-12 Imputation methods can do muchto enable data points to be combined and to checkfor possible bias.13

Conversely, general population-based longitu-dinal studies tend to have four main limitations:the paucity of rare (but serious) outcomes; thepaucity of serious environmental adversities inchildhood; the fact that measurements at theoutset of the study may well not be optimal forthe major questions that need to be posed atfollow-up; and the way that biases may be intro-duced through changes over time (which havebeen considerable for height and IQ). The com-bining of longitudinal studies beginning at dif-ferent times can help mitigate this time changeproblem.13 The long-term follow-up of the Isle ofWight sample from childhood/adolescence intomiddle age constitutes a case in point. It has pro-vided some really useful findings, such as thepredictive importance of irritability for suicidalbehavior in adult life.10 Recoding of data to fit with

current diagnostic concepts did much to improve

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the comparability of measurements but was limitedin relation to disorders for which the data failed toinclude features currently considered crucial.

High-Risk SamplesHigh-risk samples aim to remedy some of theseproblems. Some high-risk studies are concernedwith rather generic risks such as social disadvan-tage but, unless the risk is more specific, it isdifficult to identify mechanisms. The examplesthe authors provide are of the specific variety.First, the high-risk focus should allow an ade-quate number of rare but serious outcomes.Thus, the Edinburgh study14 used a sample in

hich the participants were without diagnosablechizophrenia at the initiation of the follow-up,ut, because they had at least two relatives withchizophrenia, there was a markedly increasedisk that some participants would developchizophrenia. The follow-up from late adoles-ence into adult life bore out that expectation andnabled the identification of the main predictiveariables. Of course, it was essential to check theepresentativeness of the sample with respect to theigh-risk feature, and other research was necessary

o determine how far the findings could be gener-lized to the development of schizophrenia in in-ividuals without a familial loading.

Second, the high-risk strategy provides a specialpportunity to examine the features associated withscape from risk, meaning a good outcome despiteigh-risk features when younger. The follow-uptudy to age 70 years by Sampson and Laub15,16 of

the Gluecks’ sample of incarcerated male adoles-cent delinquents (plus a non-delinquent compari-son group) provides the most striking successfulexample of this. Among other things, it allowed forthe identification of crucial “turning points” inadult life associated with marriage17 and militaryservice.18

Third, provided the mode of measurement per-mits the identification of unexpected outcomes, itcan identify sequelae that were neither predictednor in keeping with conventional diagnostic cate-gories. The identification by Clegg et al.19 of majorsocial deficits in adulthood in male subjects whohad shown a serious receptive language impair-ment in early childhood is a case in point.20 Thedemonstration by Maughan et al.21 of spellingdeficits in adult life after severe reading difficultiesin childhood constitutes another example.

In all cases it was crucial that measurement was

not tied to existing diagnostic categories,22 and that

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an appropriate comparison sample was used (ifonly because changes over time are a commonhazard). As with all longitudinal studies, attentionto (and correction for) attrition biases was essential.

Longitudinal Studies Involving a “NaturalExperiment” DesignThe third class of longitudinal study is thatwhich incorporates some form of “natural exper-iment” strategy.23,24 Longitudinal studies of allkinds have the asset of being able to examine causalorder (i.e., did the putative risk factor truly precedethe outcomes being studied?) but cannot justify acausal inference. That is because although the riskvariable may refer to an environment, that does notmean that the mediation of the route to psychopa-thology is environmental. Several rather differenttypes of “natural experiment” may make it possibleto get much closer to a valid causal inference. Allinvolve some stratagem that pulls apart variablesthat ordinarily go together.25

For example, prenatal causes can be examinedby comparing pregnancies in which the riskfactor (such as maternal smoking) operated withthose in the same mother when the risk factorwas not present. Obel et al.26 made such a com-parison using a very large Scandinavian cohort.The impact of maternal smoking on the develop-ment of attention-deficit/hyperactivity disorderreached a statistically insignificant level whenbased on this sibling comparison—suggestingthat the initial crude comparison provided anartifactually positive result. Interestingly, andimportantly, the prior use of statistical controlsfor possible confounding variables failed to re-move the artifact. This constitutes a reminder ofthe major difficulties that are always presentwhen trying to deal with confounders.27 Thedesign is a good one but it leaves open thequestion of why the mothers smoked during onepregnancy but not during another pregnancy.

Rice et al.28 and Thapar et al.29 tackled thesame topic (of maternal smoking) another wayby using an assisted conception design. Theyargued that possible genetic mediation could beruled out by comparing pregnancies resultingfrom methods that maintained the genetic linkbetween mother and child (as with donatedsperm) and those that did not (as with donatedeggs). The findings showed that the increase inattention-deficit/hyperactivity disorder or anti-

social outcomes applied only when the genetic

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link was present—making a prenatal environ-mental cause unlikely.

Yet another “natural experiment” arises when arisk or protective variable occurs only at a particularpoint in time in a specific population. The analyses ofSampson et al.17 of the effects of marriage on criminalctivities provides an excellent example of the valuef this approach, but the strategy is even more pow-rful when the relevant variable is outside the controlf the individual being studied (obviously, marriageid not fulfill that criterion).

A follow-up study into adolescence of childrenemoved from their biological parents because ofbuse or neglect in infancy (often followed byultiple foster family or institutional placements)

y Duyme et al.30 constituted a different type ofnatural experiment. The sample was restricted tothose adopted from 4 to 6 years of age and who hadan IQ test before adoption showing an IQ from 60 to86. Follow-up was 11 to 18 years and included anindividually administered IQ and an assessment ofthe socioeconomic position of the adoptive family.Not surprisingly, given the much improved life cir-cumstances, the mean IQ at follow-up (91) was sub-stantially higher than that before adoption (78). Thenatural experiment, and therefore the causal infer-ence, derived from the opportunity to determinewhether the extent of the increase in IQ was system-atically related to the qualities of the adoptive homeenvironment. The results showed that it was (with a19-point increase in the highest social adoptive groupcompared with 8 in the lowest). Although havingmany design strengths, this study was limited by thevery special requirements for inclusion in the sample,the lack of a comparison group, the possibility ofselective placement, and the lack of direct measure-ments of the qualities of the adoptive homes.

The English and Romanian Adoptee StudyThe successful use of “natural experiment” strate-gies requires careful attention to the limitations ofeach design and the combined application of de-signs with contrasting but complementary sets ofstrengths and limitations. Even in combination,true causation cannot be proved with the certaintyobtained in an experimental study, but it may wellbe possible to show that some causal hypothesis isunlikely to be correct (as with the maternal smok-ing example). Also, “natural experiments” have theadvantage over many types of experiment becausethey deal with naturally occurring circumstances as

they apply to humans.

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The English and Romanian Adoptee Study31

was a “natural experiment” in some respects simi-lar to the adoption study by Duyme et al.,30 but itsought to improve on its scientific strengths by theuse of multiple data points, a comparison group,and a focus on the timing of a particular specificadversity (namely institutional deprivation). Its pri-mary importance was the unusual circumstancethat institutional deprivation was not preceded, orfollowed, by other forms of deprivation or disad-vantage. Also, the study was unique in its clearseparation of psychosocial deprivation and subnu-trition. In addition, it constituted a particularlyrigorous “natural experiment” because of 10 keyfeatures. First, there was a major discontinuitybetween an appalling degree of deprivation in theRomanian institutions in which the children spenttheir early life and the somewhat above averagerearing conditions in the adoptive homes in theUnited Kingdom to which they moved. Second, thetransition took place over a short period and couldbe accurately dated. Third, the children were bornin an institution or moved into one within the earlyweeks of life. That meant that, unlike almost allprevious studies of effects of institutional care, thechildren were extremely unlikely to have beenplaced in the institution because of a pre-existinghandicap. Fourth, before the fall of the Ceausçescuregime, children in institutions had not been ad-opted and scarcely any returned to their biologicalfamilies. Accordingly, there was no selection withrespect to which children had remained in theinstitution, because they all had remained there.

Fifth, the Romanian authorities decided whichchildren could be considered for adoption, thusmarkedly decreasing the possibilities of selectiveparental choice. Obviously, too, the children hadno choice on what happened to them. Sixth,although not a requirement of the study, no childin the sample returned to a Romanian institution.Seventh, research by others had shown the verypoor outcomes for children who remained in Ro-manian institutions, making a comparison groupunnecessary. Eighth, however, to focus on thelong-term effects of depriving institutional care,there was a group of nondeprived children ad-opted within the United Kingdom to control forany effects of adoption. Ninth, a longitudinal de-sign with measurements at ages 4, 6, 11, and 15years was used to study within-individual changeover time (and not just between-group differences).

Tenth, the range of ages up to which institutional

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are continued enabled possible dose-response andensitive period effects to be examined.

With even the best designed “natural experi-ents,” it is always essential to undertake system-

tic checks to determine whether any biases mightave crept in. There were four that were possiblyelevant. First, despite the very early placement innstitutions, negative developmental sequelaeould have resulted from preinstitutional hazardsuch as extreme prematurity or the fetal alcoholyndrome. The authors searched all available re-ords, and on their reports four children had such aazard. These were therefore excluded from allnalyses, as were two children from the compari-on group (on the same grounds).

Second, nearly two fifths (39%) of those adopt-ng from Romania had one or more birth childrenompared with only 4% of those adopting fromithin the United Kingdom. About one fourth

23%) stated that altruism (rather than infertility)as their main motive in adoption. This was lower

han the 39% in some parents who were infertileith a new partner. Parents adopting for altruistic

easons were more likely to be regular churchgoersnd they were slightly more likely to have adoptedn older child. Any of these differences might haveiased the outcome findings and, hence, the au-hors determined whether any of these features

ere associated with variations in outcome. Thendings showed that they were not and, therefore,ould not bias the analyses.31

Third, as in any study, attention had to be paidto possible biases brought about by selective attri-tion. Fortunately, despite the follow-up lasting lon-ger than 10 years, attrition was very low, with dataavailable on 91% of adoptees and 90% of thecomparison group at the midadolescent follow-up.The availability of multiple data sources meant thatattrition was not a problem and analyses showedthat there were no attrition-related biases.

Fourth, because there were small gender differ-ences among the groups, it was necessary to deter-mine whether any of these were associated withdifferences in outcome. None were, thus obviatingthe use of separate analyses for male and for femalesubjects.

METHODOverall Design of the English and RomanianAdoptee Study and Present ReportThe overall findings to age 15 years have been re-ported in a Society for Research in Child Development

monograph.31 That provides an essential backcloth

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with respect to research design, measurements, andanalysis. However, in the present report the authorspresent new findings that focus on the children whospent the whole of their life in institutional care up tothe time of adoption and who exhibited no significantoverall subnutrition as indexed by their body weightat the time of leaving the institution to go to theiradoptive family, hereafter termed the “pure” psycho-social deprivation group. In the monograph, a range ofmultivariate analyses was undertaken to determinewhether the psychosocial deprivation findings mightbe a function of associated subnutrition. The analysesshowed that they were not. However, the finding of asignificant effect after controlling for subnutrition isnot the same as showing an effect in the absence ofsubnutrition.32 This article therefore focuses on the“pure” psychosocial deprivation group. In the originalanalysis, the authors showed that, contrary to initialexpectations, the group who left institutional carebefore the age of 6 months had no significant deficitson any of the authors’ measurements at the age of 11years. Then, from 6 to 12 months of age, there was alarge stepwise increase in deficits and no dose-responseassociation with duration of deprivation thereafter.Accordingly, the authors pooled all the children whoexperienced institutional care beyond the age of 6months, having shown that there was no significantassociation with duration of institutional care beyond6 months. Similarly, because the authors found noeffects of institutional care that ceased by age 6 months,the authors created a composite comparison group madeup of those whose institutional care ceased by 6 months,those who had not experienced institutional care butwho had experienced deprivation in a family setting, andthe within-U.K. adoptees who also had not experiencedinstitutional care. The justification was tested by check-ing for significant differences among these groups; nonewas found.31 In summary, all the main analyses concernjust two groups: the 27 individuals with “pure” psycho-social deprivation and a composite comparison groupsimilarly without subnutrition, (n � 81). However, inaddition, a subsidiary comparison between the psychos-ocial deprivation group (n � 27) and those with subnu-trition (n � 50) was required for methodologic checks.

For all these purposes, the focus was on fouroutcomes that seemed to be specific to deprivation:quasi-autism, disinhibited attachment, inattention/overactivity, and cognitive impairment. Quasi-autismreferred to a pattern that showed autistic-like features(particularly, intense circumscribed interests) butwhich differed from “ordinary” autism in greatersocial interest and flexibility. Disinhibited attachmentinvolved a disregard of social boundaries and an unduefamiliarity with strangers. Inattention/overactivity wascharacterized by persistent inattention and overactivityassociated with one or other of the first two patterns.Cognitive impairment was defined as an IQ below 80

accompanied by one of the first two patterns. All four

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patterns were very strongly associated with continuingservice needs and usage up to age 15 years.31

There was a significant, but modest, overlap amongthese four patterns. The coherence, however, was notin the statistical associations among the patterns, butrather in the very similar strong and specific associa-tions with deprivation lasting beyond the age of 6months. The validation of the two composite groupsused in the present analyses was based on this postulatedoverall deprivation-specific pattern (DSP) and it cannotnecessarily be assumed that this approach would bejustifiable for other outcomes. Nevertheless, rather to theauthors’ surprise, they found that institutional depriva-tion was not associated with an increase in other forms ofpsychopathology that were not accompanied, or devel-opmentally preceded, by one of the defined DSPs.

In these new analyses, the authors focus on DSPsand use the same composite comparison group (apartfrom requiring both groups to exclude those withsubnutrition). The conceptual issues and details of mea-surement were considered in detail in the authors’ mono-graph31 and will not be further discussed here. Never-heless, it was essential to begin by determining whetherhe 6-month split in duration of deprivation worked welln the revised group studied, namely those children whopent all their life in institutional care up to the time ofdoption, and not just most of it, and who were notubnourished as indexed by a body weight at the time ofeaving the institution that was within a 1.5 standardeviation (SD) limit in relation to U.K. population norms.fter excluding the very few children with a prenatal

ondition (such as fetal alcohol syndrome) that mightave had a causal effect on outcome and the two indi-iduals with missing data, that meant an effective sampleize of 27 individuals whose “pure” psychosocial depri-ation continued until after the age of 6 months and 30hose institutional care ceased before 6 months.

There were 114 young people in the original com-osite comparison group, of whom 81 did not showubnutrition. That the subjects without subnutritionere within the normal weight range was shown by

he finding that their average weight on leaving thenstitution was marginally, but significantly, higherhan that of the noninstitutionally deprived childrendopted directly from family care.33

RESULTSIn the “pure” psychosocial deprivation group, therate of DSP at age 15 years was substantially andsignificantly higher in the 27 whose institutional carelasted beyond the point when the child reached 6months and the 30 whose care lasted less than 6months (in both cases, the number excludes thosewith missing data). The difference in the pure psy-chosocial deprivation group was 45.5% versus 1.3%

(exact test, p � .0001). It was evident that “pure”

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psychosocial deprivation did differ in its effects ac-cording to whether the children were older oryounger than 6 months at the time of leaving theinstitution.

The “pure” psychosocial deprivation groupwhose institutional care extended to an age of atleast 6 months had a Denver developmental quo-tient of 42.7 at age 4 years compared with a mean of88.9 in the comparison group (Figure 1). Becausethere were no contemporaneous data on the Den-ver developmental quotient, this had to be asses-sed retrospectively. However, detailed analysesstrongly suggested their validity.31 By the age of 6years, the respective means were 83.9 and 107.5 onthe McCarthy General Cognitive Index (G.C.I.)—avery substantial, but incomplete, catch-up. The4-year data were available only for those childrenin the sample who were seen by this age. This wasa small proportion of the comparison group, butthose included were very comparable with thosenot included. However, the sample available forthis retrospectively assessed Denver developmen-tal quotient was much the same at all ages for the“pure deprivation” group. The catch-up from 4 to 6years was considerable but there was a small non-significant further catch-up of 4.3 points from 11to 15 years when the same test (WISC) was used.Post hoc tests (Sidak corrected) showed significantdifferences between groups at all assessment ages(p � .001). A mixed linear model showed a meaneffect of age (F3,226.9 � 8.29, p � .0001) and durationof deprivation (F1,112.8 � 32.93, p � .0001). Theinteraction effect between age and duration ofdeprivation fell short of significance (F3,226.9 � 2.24,p � .085). Post hoc tests (Sidak corrected) showed

FIGURE 1 Developmental quotient and IQ over time.Note: ID � institutional deprivation.

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ignificant differences between groups at all assess-ent ages (p � .001).At the age of 15 years, 45.4% of the children

ith “pure” psychosocial deprivation showed aSP compared with 1.3% in the comparisonroup—a statistically significant (exact test, p �

0001) and large difference (Figure 2).As in the total sample, subnutrition was asso-

iated with a large decrease in head circumfer-nce even if the institutional care ceased beforehe children (n � 30) were 6 months of age (�2.89D) compared with a similar decrease (�2.81 SD)n those whose care lasted longer (n � 47). This

was associated with a similar decrease in heightand weight, so that it may be inferred that thesmall head size was part of a general decrease inbody size that started to be evident probablyfrom the time that subnutrition was evident(“probably” because the authors lacked measure-ments in the early months). In marked contrast,“pure” psychosocial deprivation had no markedeffect until after 6 months. Thereafter, however,there was a very large decrease in head size(�2.43 SD). Analysis of variance results showed asignificant interaction between age at leavinginstitutional care and subnutrition (F1,125 � 8.80,p � .004; Figure 3). It is known from otheresearch that brain size is strongly associatedith head size, implying that brain growthrives head growth. The same was found in theuthors’ pilot magnetic resonance imagingtudy,34 but, unfortunately, the small sample

included very few children without subnutritionso that the findings cannot be used directly here.

Figure 4 shows the standardized head circum-

FIGURE 2 Rate of deprivation-specific patterns (DSP)n the pooled comparison group and the puresychosocial deprivation group. Note: ID � institutional

deprivation.

ference scores at ages 6, 11, and 15 years for the

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children without subnutrition, those with subnutri-tion, and the comparison group. The comparisongroup findings for those with and without subnutri-tion are not identical because the comparison grouphad to omit the subnourished in the comparison withthe subnourished institutional children. Mixed linearmodels showed statistically significant main effects oftime, namely catch-up (F2,132.1 � 30.73, p � .001) ofsubnutrition, small heads (F1,107.2 � 12.91, p � .001),and DSP status (F2,107.6 � 5.52, p � .005). Althoughthere was a different pattern in the subnourished andpure psychosocial deprivation groups, no significantinteractions were found (F � 1.89, p � .190 for allcomparisons).

FIGURE 3 Differences in head circumference accordingto presence of subnutrition in individuals whose institutionalcare did or did not last beyond the child’s age of 6months. Note: ID � institutional deprivation.

FIGURE 4 Standardized head circumference over time indeprivation-specific pattern.

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DISCUSSIONThe evidence that “pure” psychosocial depriva-tion had a major effect in leading to DSPs isstrong and highly consistent. The evidence isparticularly persuasive because it is based ondirect measurement of the “pure” effects, ratherthan analyses partialing out the variance in alarger group. It should be noted, too, that studyof the entire sample31 showed that subnutritionhad a significant, but relatively small, effect onintelligence but not on any other outcome andnot on DSPs as a whole. This is an importantfinding because no previous study has provideda clear distinction between “pure” psychosocialdeprivation and deprivation that also involvessubnutrition. Moreover, there was no evidenceof interactive effects. Even so, it is necessary toask whether the psychosocial deprivation wastruly pure. The key point in this connection isthat there was no subnutrition as indexed bybody weight, but no measurement was avail-able of the quality and balance of the diet in theinstitution. What is known about feeding pat-terns in the Romanian institutions suggests that it isunlikely to have been good. Accordingly, it re-mains possible that malnutrition (rather than sub-nutrition) could have potentiated the ill effects ofpsychosocial deprivation. The authors do not havethe measurements required to test that hypothesis.What is clear, however, is that the findings onsubnutrition suggest that, if malnutrition plays arole, it is most unlikely to be indexed by the degreeof subnutrition.

ups with and without subnutrition. Note: DSP �

gro

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The next question is whether the effects might bea consequence of experiences before, rather thanduring, institutional care. In the total sample, stepswere taken to exclude children with evidence ofprenatal effects (such as fetal alcohol syndrome),but inevitably this had to be reliant on the presenceof observable congenital anomalies. Low birthweight was another possibility, but it was a veryweak predictor of outcomes in the total sample.However, the most convincing evidence against aprenatal effect was the strength of the 6-monthcutoff for depriving institutional care. There is noplausible way that that could be accounted for byprenatal risk factors, identified or nonidentified.

Genetic risk factors constitute a similar situationbut the 6-month effect makes those implausible asmain causal influences, as does the fact that thechildren had been reared in institutions for thewhole of their life before adoption. However, gene-environment interactions remain a possibility, withgenetic influences operating through effects onsusceptibility to environments rather than maineffects on outcomes. Indeed, the authors foundsuggestive evidence for gene-environment interac-tions regarding two specific non-DSP outcomes35,36

but not for DSP as such.The conclusion, or inference, that psychosocial

deprivation in the institution constituted the maincausal influence on DSP needs to be tested moredirectly, and not just by exclusion. The finding that“pure” psychosocial deprivation had a large effect onhead growth after it had lasted for 6 months providesstrong evidence of a major neural impact. Because ofthe authors’ focus on deprivation that began at, orsoon after, birth and lasted throughout the period upto leaving the institution, there is no realistic chance ofits being a function of social selection, and because thedeprivation preceded the impaired head growth, it isimplausible that there was reverse causation. Thefinding that the head growth impairment pattern wasso different from that associated with subnutrition isimportant because it reinforces the conclusion that theneural effect was truly a function of psychosocialdeprivation rather than subnutrition. The finding inthe total sample31 that the effect of deprivation onDSP was as marked at 15 years as it had been at 11years, and previously at 6 years, provides anothercrucial piece of evidence. That applied equallystrongly to “pure” psychosocial deprivation. As al-ways in science, the question has to be posed as towhich explanation is most likely to be correct—in this

case, the postulated causal effect of “pure” depriva-

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ion. There is strong evidence in support, and noonvincing contrary evidence.37

The main scientific implication of the findingsconcerns the value of seeking to separate the dif-ferent facets of deprivation and the importance offinding that “pure” psychosocial deprivation in-volves neural effects in the form of impaired headgrowth and, by extrapolation, impaired braingrowth. More detailed brain imaging studies arerequired to identify more clearly the brain changes;such studies are planned. The main clinical implica-tion is that profound institutional deprivation resultsin rather unusual and specific psychopathologic pat-terns. Clinicians are often skeptical about claims thatadverse experiences that cease in early childhood leadto maladaptive behavior in adolescence more than adecade later. The authors’ findings showed the realityand importance of such enduring effects.

In summary, the natural experiment design theauthors used provided powerful evidence of acausal effect of “pure” psychosocial deprivation onthe liability to DSPs. Although a nonexperimentaldesign cannot provide definitive proof of causa-tion, a noncausal explanation is highly unlikely tobe correct. Nevertheless, important questions havestill to be addressed, the most important beingwhether a similar effect on DSPs can derive fromprofound deprivation within a family context. &

Accepted May 22, 2012.

Dr. Rutter is with the Medical Research Council Social, Genetic, andDevelopmental Psychiatry Centre, King’s College London. Dr. Kumsta iswith the University of Freiburg. Dr. Schlotz is with the University ofRegensburg. Dr. Sonuga-Barke is with the University of Southampton andGhent University.

This article is part of a special series on recent findings and progressin the fields of birth cohort and longitudinal studies of child andadolescent psychopathology. This special series is intended to show-case some of the most important new findings and promising leads inthe study of developmental psychopathology over time, and todemonstrate the Journal’s renewed commitment to publishing thehighest quality articles on the topic. Each article is in part a review ofthe most important findings to date from the study and in part originalresearch to allow readers to learn about a new research finding witha more complete context of the study than is usually possible.Disclosure: Dr. Sonuga-Barke has served as a consultant for and on thespeakers’ board for Shire and UCB Pharma and has served on theadvisory board for Shire, Flynn Pharma, UCB Pharma, and AstraZeneca.He has received research support from Janssen-Cilag, Shire, Qbtech, andFlynn Pharma, and has received conference support from Shire.Correspondence to Michael Rutter, M.D., P.O. 80, Social,Genetic, and Developmental Psychiatry Centre, Institute ofPsychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF,UK; e-mail: camilla.azis@kcl.ac.uk

0890-8567/$36.00/©2012 American Academy of Child andAdolescent Psychiatry

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AL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY

VOLUME 51 NUMBER 8 AUGUST 2012