SIMON WATSON/TAXI/GETTY

Vol 460|9 July 2009

Can biologicalindicators predict the
future mental healthof our children?

Biomarkers in psychiatry
Ilina Singh and Nikolas Rose

The use of biomarkers to predict human behaviour and psychiatric disorders raises social and ethicalissues, which must be resolved by collaborative efforts.
Psychiatry has long beena second-class citizen inscience and medicine.
Despite much effort, thecauses of many psychiatric disorders remain
unclear, and it has beendifficult even to categoHORIZONS
rize such disorders precisely. In the past decade,however, there has been a large shift towards
incorporating biomarkers into psychiatry(Fig. 1), and there is hope that such biologicalindicators will improve psychiatric diagnoses
by underpinning them with physiological evidence (Boxes 1 and 2). But biomarkers promise far more than a basis for better diagnoses.
They could assist in predicting the course of an
illness in an individual and in tailoring treatment. And they could be used to predict thedevelopment of not only psychiatric disorders
but also certain behaviours, personality traits
and mental or emotional capacity.
Scientific innovations that will ultimately
improve psychiatric outcomes and general wellbeing are to be welcomed. But they must be
scrutinized to assess their value to the general202

public. Despite the wealth of research into
biomarkers and the considerable interest in
their use in clinical and non-clinical situations,
there has been little discussion of the social,
ethical and legal problems posed by their use
in psychiatry. Here we set out the key challenges in this area. We focus on interventions
in children and adolescents, particularly those
aimed at preventing behavioural problems.
The identification of biomarkers in these agegroups forms an important research agenda
and the initial pathways through which thisresearch is being translated from the laboratory
to the clinic, as well as the classroom and otherlocations, can already be observed.

The promise of biomarkers
At present, psychiatric disorders are diagnosed
on the basis of signs, symptoms and course ofillness, according to the classifications in the
fourth edition of the Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV). Finding a biological or physiological marker, rather
than relying on behavioural symptoms andsigns, might provide a more precise means ofdiagnosis, thereby aligning psychiatric classification with classification systems used in other© 2009 Macmillan Publishers Limited. All rights reserved

areas of medicine1. Such methods might also
go further and help to re-organize the DSM
system of classification, offering a counter tothe swelling catalogue of categories, each with
its lengthening lists of behavioural symptoms
and subclassifications that have no differentiated aetiology.
Moreover, biomarkers might be used to predict the potential for developing a particulardisorder. This is of particular significance inchild and adolescent psychiatry. Genetic screening and neuroimaging — the main techniques
for identifying biomarkers — could be used toassess children before symptoms appear. And
existing childhood disorders are now themselves being viewed as ‘biomarkers’ for the riskof developing more severe disorders.
In this sense, biomarkers promise to be themost powerful psychiatric tool since the discovery of antipsychotic drugs — a biologicalmeans of predicting not only the developmentof a disorder but also its course and outcome.
Biomarkers could therefore inform the type,timing and course of interventions, and they
could allow disorders to be subtyped based on
physiological criteria, creating a more personalized approach to psychiatric treatments.

HORIZONSNATURE|Vol 460|9 July 2009

the ethical dilemmas they raise, need to be analysed. And the analyses should not be viewed
as merely the ‘social work’ adjunct to the ‘hard
science’. Research into the social and ethicalprocesses of translation, and into the challenges
that are often faced, should inform the work of
researchers themselves and can help to ensurethat this research does result in improvements
in social practice. For example, challenges tothe validity of psychiatric diagnoses have led
to increasingly complex models of conditions
such as attention deficit hyperactivity disorder (ADHD), as well as efforts to validate andstandardize diagnoses for these conditions8.
We have three main concerns about thepotential use of psychiatric biomarkers. Whatis the best way to communicate the idea of a‘risk profile’, and how might this affect personal identity? Given that human behaviour
and psychiatric disorders arise from a complex set of factors, how can this complexity
be retained when using information aboutbiomarkers in the clinic and community? And
what issues might arise from the commercialization of biomarkers, and how should they be
addressed?

Personal identity and risk profiles
For children and adolescents, it has been common practice to identify those ‘at risk’ of psychiatric disorders, educational failure, or socialand emotional difficulties, and to provide themwith special resources as part of a social programme. However, identifying such children
by using genetic and neurobiological biomarker information (potentially before symptoms
develop) will be new. The lack of predictive
power of biomarkers as risk factors for individuals, and the probabilistic nature of risk assessments based on them, raises specific issues. We
are particularly concerned about biomarkers

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The use of biomarkers in any of these contexts
presents many challenges. A biomarker — forexample, a certain pattern of brain activity —is not the cause of a disorder. So the current
interest in biomarkers is a sign that psychiatry
has undergone a methodological shift, awayfrom searching for the causes of a condition
towards estimating the probability that thecondition is present or will develop. One challenge arising from this approach is that individual variables associated with an increased
risk of developing a condition, for example
information about a single biomarker, usually have small effect sizes: that is, when usedalone, they are not robust predictors of thepresence or absence of a condition. However,when bundled into an algorithm that incorporates other biomarker information, as well associal and environmental risk factors (such as
prenatal exposure to alcohol, postnatal exposure to lead, family poverty and child abuse),biomarkers could be powerful predictors thata disorder will develop. However, biomarker
information will always be a statement of theprobability that a condition will develop: that
is, a statement about the risk of developing thatcondition. Therefore, even risk algorithms thatare powerful predictors will retain a degree of

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The challenges

uncertainty. The hope is that this uncertainty
will lessen over time, as highly predictive variables become easier to identify.
Many psychiatric researchers, however, havedeep-seated doubts about whether the current
methods for identifying biomarkers — such as
genome-wide association studies (which searchfor genetic markers associated with diseaserisk) and imaging of the brain region of interest, which are based on studies of groups —can uncover biomarkers with strong predictive
value for a specific individual. There are also
doubts that biomarkers will have translational
applications within the next decade in a manner that would allow biomarker information to
guide clinical, educational and legal practices
and policies substantively.
Outside specialist circles, these doubts areoften minimized, and questionable biomarkers can begin to take on scientific and social
importance. This process of overgeneralization and oversimplification has occurred on
many occasions, for a long list of neuroscientific discoveries, including claims about the‘gene for aggression’ in humans and about the
implications of ‘mirror neurons’ in non-humanprimates (neurons that are active when an animal carries out a particular action or observes
another animal carry out the same action),
which have been equated with these animals
having human-like empathy6,7. These kinds ofoverstated claim are even more evident whencommercial enterprises have an interest in promoting the diagnostic value of a test.
Moreover, the translation of research fromthe laboratory to particular social practices,such as medicine or education, is not determined by the scientific innovation itself but
by social and political decisions that are often
shaped by many factors other than scientificevidence. These processes of translation, andNumber of articles published

But the potential impact of psychiatricbiomarkers extends beyond the clinic, to arenas
responsible for the growth and development ofchildren as productive citizens: the classroom
and the courtroom. For example, in the United
Kingdom, a new national agenda of ensuring‘mental capital and well-being’ is grounded in
new science that has transformed the understanding of child development and learning2.
Enthusiasts for educational programmes basedon neuroscience argue that neuroscientificevidence should be applied at an early age andwith a broad remit, not only informing how
children are taught and how classrooms are
structured but also helping to identify developmental challenges — such as impulsivenessand learning difficulties — that are thought
to be associated with later psychiatric, educational and social problems3. In the courtroom
context, neuroscientific understanding of how
the brain develops is being used to inform juvenile justice decisions. A landmark 2005 decision in the US Supreme Court that overturned
the death penalty for juveniles (those under 18
years of age) is thought to have been strongly
influenced by neuroscientific evidence about
the capacities of the ‘adolescent brain’ to control impulsive and risk-taking behaviours4.
In addition, research efforts are underway toidentify brain-based biomarkers associatedwith juvenile delinquency so that neurodevelopmental risks can be built into models to
predict youth antisocial behaviour5. These nonclinical applications of psychiatric biomarkers
suggest the extent to which biomarkers could
come to shape the lives of ‘normal’ individuals,
especially children.

Year

Figure 1 | Rising interest in biomarkers and psychiatry. In the past decade, psychiatric researchers,
doctors and policymakers have become increasingly interested in finding objective biomarkers
that will provide a more accurate and precise means of assessing actual and potential psychiatricconditions. This increased attention to biomarkers is reflected by the rise in the number of scientificarticles on this topic. Data were obtained from a search of the ISI Web of Knowledge in May 2009 forarticles with the term ‘biomarker’ and the word stem ‘psy’ in the topic field. No articles were indexed
by ISI for the years 1986, 1987 and 2002. It should be noted that some early articles may have focusedon non-psychiatric conditions and only tangentially addressed the psychiatric aspects. (Courtesy of J.
Abi Rached, The London School of Economics and Political Science, UK.)
© 2009 Macmillan Publishers Limited. All rights reserved

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HORIZONSNATURE|Vol 460|9 July 2009

Box 1 | What are biomarkers?
A biomarker is a characteristicthat is objectively measured
and evaluated as an indicatorof normal biologicalprocesses, pathogenic
processes or pharmacologicalresponses to a therapeuticintervention40.
Different markers canbe used to make various
assessments: to diagnosea condition; to predict thenatural outcome for anindividual with this condition;
to predict whether theindividual will benefit froma particular treatment andhow aggressively to treat theindividual; and to assess anindividual’s response to thistreatment.
In a psychiatric context,
biomarkers could be used todetect and assess, or predictthe development of, not only
psychiatric disorders but also
personality or behaviouraltraits, and emotionalor cognitive capacity.
Biomarkers could also be
used to inform treatment
decisions. Examples ofbiomarkers are:•specific variations in skinconductivity;•specific patterns of neuralthat identify the risk of behavioural problems
developing in children, as well as the risk ofpsychiatric diagnoses such as ADHD, conductdisorder and oppositional defiant disorder, all ofwhich are directly or indirectly linked to delinquency, substance abuse, antisocial behaviour,
personality disorder and/or criminality. Because
antisocial behaviour by young people is a majorsocial problem in many countries, if biomarkers for such behaviours are found to be present
during early childhood screening, then children
might be subject to intrusive medical interventions that focus on individual-level risk factors
rather than on social and environmental risk
factors9. Indeed, given the increasing use ofpsychotropic medication in very young children(3 to 5 years of age)10, and the problem of inconsistently applied diagnostic thresholds in childpsychiatry11, it is possible that young children
with a high risk profile for antisocial or criminal
behaviour could be given drug treatments at a
pre-symptomatic or subclinical stage.
The problems inherent in the probabilistic nature of risk assessment are not uniqueto psychiatry. But the consequences of psychiatric risk profiling for children and theirfamilies might differ qualitatively from thoseof profiling other medical conditions in childhood. At present, it is unclear what will happen
when children are identified as being at risk ofdeveloping a psychiatric disorder or antisocial
behaviour in societies that are suffused by anxiety about the adverse social consequences ofsuch conditions. As risk profiling of children,using biomarkers, begins to replace efforts to
identify biological or environmental causes,
will ideas about the identity and the capacityof individuals begin to change? That is, howwill people feel about themselves given theirrisk profile, and will others perceive them differently? Will ‘risk’ and ‘potential’ eventually
dominate ideas of personal identity, healthstatus and opportunity in rigid, coercive or
stigmatizing ways? Will these ideas become
institutionalized within education, law andpolicy? And how will such changes affect the204

activity in particular brain
regions, detected byimaging techniques, suchas functional magnetic
resonance imaging (fMRI)
and positron-emission
tomography (PET);•specific genetic sequencesor single-nucleotide
polymorphisms, identified bygenetic screening;•specific endophenotypes(intermediate traits in the
chain of causality between
genes and diseases),such as biochemical,
neurophysiological orneuropsychological features.

life trajectories of children identified as at risk
early in life?
There is a body of research on risk perception and stigma that addresses how people’s
judgements and beliefs about the genetic basisof psychiatric disorders affect their self-identity
and their attitudes towards others with psychiatric diagnoses12–14. However, there has been
little research on how these perceptions andattitudes might differ when they are shaped byinformation based on markers whose predictive value is probabilistic, although there are
ongoing studies of these issues as they arisein the context of personal genomics15. Such
research needs to be expanded to examine
issues involved in the screening of individuals for the presence of psychiatric biomarkers,
in order to evaluate the potential for children
developing a negative ‘risk identity’. It is also
important to assess how biomarker information might reshape the beliefs, practices anddecision-making of the people in a child’s
environment, including parents, teachers andhealth providers. And, given that young people
themselves discuss these issues and share information about psychiatric conditions and interventions, it is important to understand further
how biomarker information might affect bothyoung people’s identities as individuals and as
members of various groups and their relationships with their peers.
Discoveries in neuroscience can, however,
have a positive effect, particularly when they
converge with patient activism, resulting in
broader conceptions of self and possibility.
For example, there are strong claims by some
autism researchers and autism patient groups
that biomarkers associated with autism indicate a divergence from the norm that is a sourceof creativity and special cognitive capacities16.
In this case, how does biomarker information
motivate individuals instead of inducing afatalistic attitude? And how can such resiliencebe promoted in varied contexts, such as families and classrooms, when there is challenging
news regarding a child’s risk profile?
© 2009 Macmillan Publishers Limited. All rights reserved

Another important issue is the potential
consequences of claims about differences inrisk prevalence between population groups. As
is the case for physical diseases, evidence thata certain condition is more prevalent in one
ethnic group than another is a double-edged
sword. On the one hand, such evidence supports the development of strategies to tackle
those disorders. On the other hand, it can leadto discrimination on biological or genetic
grounds17,18. Although some people claim that
identifying a high level of risk among ethnic
minorities, single parents or the very poor canhelp to direct more attention and resources
to the problems encountered by such groups,
there is evidence that people in these groups
are also more likely to be, and to feel, stigmatized by at-risk labels and psychiatric labels19.
It is also important to determine whether
children from these or other populations are
more likely to be ascribed harmful risk identities than children from majority or advantaged
groups when biomarkers are used to identify
those at risk. In particular, genetic biomarkers
that identify children from ethnic minorities
as being at risk of problem behaviours and/or
psychiatric conditions might build on existing assumptions about links between race,
genetics and behaviour. And they might havea self-reinforcing effect, leading to efforts toundertake risk screens that genetically profile
young people who have first been classified byrace or ethnicity.
The only way to explore the ‘social life’of biomarker information is to carry out aprogramme of detailed qualitative researchin which all groups of individuals who are
affected participate, including children. Sucha programme of research should accompany
current scientific research on biomarkers, even
if these studies are not yet seeking translational
outcomes. Because the expectations aroundbiomarkers are so high, it is possible that any
translational applications will be quickly implemented, without time for deliberation over thesocial and ethical issues. Prospective researchon these issues is needed to inform policies
and practices that will maximize the positive
potential of biomarker information and protect
individuals and families from harm.

Retaining complexity
Issues around communicating and explaining risks link directly to our second major
concern: that the many factors contributing
to behaviour and psychiatric conditions need
to be considered in addition to information
about biomarkers. The techniques used tomeasure biomarkers (mainly neuroimaging
and genetic screening) produce images andnumbers. These results seem to be precise
and objective and therefore have great persuasive power, often greater than is warrantedby their predictive power. Indeed, recent criticism over the level of funding of genome-wide
association studies has highlighted their failure
to uncover genetic markers that account forHORIZONSNATURE|Vol 460|9 July 2009

most of the genetic contribution to the risk ofcommon disease20,21. Similarly, magnetic resonance imaging (MRI) studies have uncoveredmuch about the basic science of brain function and structure, but the predictive utility ofbrain-based biomarkers does not match thehype surrounding their discovery22. Although
research on biomarkers is of considerable scientific interest and importance, the persuasive
power of biomarkers will be greater than theirclinical or social utility for the foreseeable
future. It is important to prevent such persuasiveness from leading to reductionist explanations for complex behaviours or conditions
in children. Information about a biomarker
can help to build a risk profile for a particularcondition or set of behaviours. But biomarkers
alone, taken out of context of environmental
influences, are unlikely ever to provide complete explanations for children’s behaviour ora forecast of how children’s lives will unfold.
Biology is not destiny: biology provides information about potentials. So how can this levelof complexity be retained when biomarkers
move from ‘the bench to the bedside’?
First, systematic assessments of the explanatory power of biomarkers for particular behavioural conditions and psychiatric diagnoses
are needed. These assessments must focus on
two areas. The accuracy and reliability of thetechniques themselves — particularly genetic
screening and neuroimaging — must be
tested. And the validity of the findings must be
assessed, given the problems with the methods
and with study design. To take functional MRI(fMRI) studies as an example, studies involving
children are often significantly underpowered23.
Moreover, applying different statistical methods
to fMRI data has been shown to deliver markedly different estimates of the significance of
associations between brain-based biomarkers
and cognitive–emotional traits24. There is also alack of normative fMRI data for children, partly
as a result of ethical concerns about scanning
healthy children; therefore, children’s scans are
frequently analysed by comparing them withadult brain scans. Finally, outcomes of fMRI
research are relevant at the population levelbut are not yet relevant for individual diagnoses
and treatments. Published studies should be
scrutinized for problems of validity, by metaanalyses for example (such as the recent critiqueof fMRI data reported in social neurosciencestudies, which describes many of the results as‘voodoo’ correlations24), and the results of such
scrutiny should be reported and debated in scientific journals.
The next task will be to disseminate theresults of these assessments in a comprehensive
programme of public engagement. Dissemination strategies could take various forms, including media appearances, teacher and student
education, publication in the popular press andartistic performances. Scientists must take up
the challenge of collaboration with a variety ofprofessionals from other disciplines, to build
a better public understanding of behaviouralconditions in children and the environmental
and biological underpinnings of these conditions. Moreover, these activities should support
the public’s ability to think critically about current neuroscientific theories and the evidence
that forms the basis of these theories, including the continuum of normal and abnormal
behaviour, interactions between genes and theenvironment, causality and the direction ofeffects, and the probabilistic nature of genetic
and neurobiological influences on behaviour and cognition. Given the public’s lack ofknowledge — misperceptions even — about
genetics, neurobiology and behaviour25–27,
one of the most important components ofthis public-engagement programme will be to
study its outcome: to examine which modes ofdissemination and education are most effective
at building an accurate public understanding inthis area, and for which populations; and which
initiatives are most likely to inspire sustained
public engagement with these issues.
In addition, the translational activities ofscientists and scientific teams who carry out
research on biomarkers in children need to beinvestigated. How do efforts to find applications
for biomarkers in the clinic, the classroom or
the juvenile courtroom accommodate complex
models of behaviours, models that are probabilistic, multidirectional and incorporate a variety of causes. And to what extent do proposed
treatments or interventions either reinforce orundermine such models? For example, the risein childhood diagnoses such as ADHD, bipolar
disorder and social anxiety disorder suggeststhat the availability of effective drug treatments(such as stimulants, antipsychotics and antidepressants) undermines multicausal explanations of childhood behaviours. If biomarkers
are used to inform strategies for treatment withpsychotropic drugs, and if such treatment isused preventively, then there is a substantial
risk that biomarkers will be seen as the primaryor ultimate cause of behavioural conditions ina child.
Finally, biomarker-based family and educational interventions for children should bemonitored by a research team that includes
professional educators, mental-health professionals, ethicists and social scientists, working
in collaboration with family representatives
and teachers. Part of the remit of such research
will be to identify the disadvantages and theadvantages of policies that are informed byresearch on biomarkers, by evaluating the longterm educational, social and behavioural outcomes for particular groups of children. It willbe especially important to carry out researchthat identifies and investigates the conditions
under which genetic and neurobiological factors may come to define an individual’s risk andpotential without appropriate attention being
paid to non-biological factors. At present, there
is a strong emphasis on early identification andintervention programmes that assure children’s
long-term mental health and positive social
contributions; therefore, a comprehensive
system of monitoring the educational, socialand ethical outcomes of such programmes forindividuals and society is essential.

Commercial issues
Biomarkers are entering the public’s awareness, through the activities of commercial
enterprises such as 23andMe and other companies that offer genetic screening and brain
scanning services directly to consumers. These
ventures promise to provide individuals withsignificant information about their risk profile
for numerous diseases and disorders, as well as
information on personality and behavioural
types. Clearly, businesses need to attract customers and will therefore emphasize what they
consider to be the benefits of their services topotential consumers. This is the case not only
for genetic tests but also for tests available onBox 2 | Status of psychiatric biomarker research
Evidence of biomarkers
associated with psychiatricdisorders is emerging fromstudies in experimental
neuroscience and psychiatricgenetics, and many of thesestudies are improving ourunderstanding of the neuralpathways and mechanisms
underlying such disorders.
But, at present, only a few
biomarkers show promise
as robust predictors of
psychiatric disorders. One
prominent example is avariant of the monoamineoxidase A gene, which
several studies have foundto be associated with riskof antisocial behaviour,but only when there is ahistory of adversity in earlychildhood41,42. This discovery
is the strongest indicator so
far that biomarker information
alone is unlikely to explain
most of the variance inobserved behaviours. Gene–
environment interaction
studies, rather than studies
that search for single genetic
polymorphisms, could deliver
more robust results that havepotential social and clinicalapplications.
In addition, researchers are
identifying endophenotypes
that can act as predictors of
behavioural and psychiatricdisorders. An example
of a robust psychiatricendophenotype is abnormal
eye-tracking movements inpatients with schizophrenia43.

© 2009 Macmillan Publishers Limited. All rights reserved

In child psychiatry, apromising endophenotype
is callous and unemotional
traits1. Several studies haveshown such traits to bestrongly associated with thedevelopment of psychopathy
in children. And although theneurobiological and genetic
basis of these traits is notwell understood, they areassociated with a variety ofbiochemical, neuroendocrineand genetic markers.
At present, althoughneuropsychological testingis sometimes used to inform
psychiatric diagnoses,
biological information derived
from brain scans or genetic
screening is not yet used inclinical psychiatry.
205

HORIZONSNATURE|Vol 460|9 July 2009

ƭ Accuracy
ƭ Validity
ƭ Predictive powerpow
ƭ Evidence-base
Evidence-based interventions
ƭ Public engage
engagement

ƭ Risk proﬁling
ƭ Social
al identities
ƭɥSocial
al beliefs
uasiveness of dataƭ Persuasivenesscationƭ Education
SocialScientiﬁc

PSYCHIATRIC
BIOMARKER
ƭ Privacyhtsƭ Children’s rights
pacityƭ Children’s capacity(for informed consent
making)and decision-making)ƭ Interventions

Legal andregulatory

EthicalCommercial

ƭɥRisk identityƭƭɥDiscriminationDisc(ag(against individuals
or mminority groups)
ƭ StigStigmaƭ Lab
Labellingƭ Validity of claims
ƭ Conﬂict of interestƭɥConﬁdentiality
ƭ Data ownershipƭ Data interpretation

Figure 2 | Issues that influence the use of biomarkers in psychiatry and beyond. As the search forpsychiatric biomarkers increasingly shapes research, as well as clinical and non-clinical settings suchas classrooms and courtrooms, many issues need to be debated, studied and resolved. These include
social, legal, ethical, commercial and scientific issues.

the Internet for everything from depression
to osteoporosis and for home test kits suchas those for measuring cholesterol levels anddetecting signs of diabetes and bowel cancer.
Many of these are a cause of concern to doctors
and regulators, who consider that they provide
information of dubious medical value and aresometimes dangerously misleading28.
We are concerned that the commercialization and marketing of biomarker data about
psychiatric conditions, personality traits, andemotional and cognitive capacities might
have harmful consequences for the ways thatfamilies and children make vital decisions
and view their future, and indeed how others
make decisions on their behalf. The companies
often argue that knowledge cannot be harmful
and that they are making access to biomedical
information more democratic29. They have alsotended to resist regulation of their activities,
branding this as paternalistic30. However, we
think that social-science research is required
to examine the extent to which such commercialization of biomedical information, andits availability on a direct-to-consumer basis,
may encourage individuals and families — andperhaps medical and non-medical professionals — to develop unrealistic ideas about
the explanatory power of this information.
For example, evidence from the United Statesshows that patients who mention an antidepressant by name to their doctor are more
likely to receive a prescription for that drug31.
So will doctors be more likely to diagnose achild as having a particular psychiatric condition — or to provide medical treatments — if
206

families come into the clinic on the basis ofbiomarker information that they have obtained
themselves?
Little is known about how those who takeadvantage of commercial screening and scanning interpret and use information about personal biomarkers. Social research on the use of
personal genetic risk information suggests that
individuals do not always reshape their lives or
identities around such information, even when
the probability of developing a severe diseaseis high32–34. But will this be the case when the
personal biomarker information is obtained bya child or by a parent acting on behalf of a child,and when the targeted biomarkers ostensibly
reveal information that is closely associatedwith personal identity (such as personality
traits, behavioural traits, and/or predisposition to certain thoughts and feelings)? Why
would parents initiate commercial genetic
screening or brain scanning for their child?
Will biomarker information that provides a
cognitive–behavioural risk profile for a young
child affect not only how parents think about
their child but also how they act on behalf ofthe child? In what circumstances might thishave positive consequences for the child, andwhen might this information do harm? Much
more information is needed about the social
and behavioural consequences of the availability of personal biomarker information forchildren before evidence-based judgements
can be made about the ethical issues raised bysuch technologies.
One key ethical issue is the capacity of children to understand the consent processes© 2009 Macmillan Publishers Limited. All rights reserved

involved in submitting to commercial screensand scans, as well as their capacity to makedecisions about the complex issues that results
often raise. To what extent, and at what age,
do children have the right to know about theirpersonal biomarker profiles? Do children havethe right to refuse to submit to genetic screensand brain scans when these are not clinicallyindicated? Conversely, should children havethe right to submit their own samples to suchcompanies or to choose to undergo brain scans
to learn more about their risk of displaying certain behaviours or traits? Research into thisissue is needed so that thresholds can be set for
the age at which children are competent to provide consent for screening and scanning and to
make informed decisions about the findings.
The regulation of children’s rights, capacity andconsent in analogous contexts, such as birthcontrol and cosmetic surgery, could inform
thinking about children’s access to personal
biomarker information.
A related area of concern is confidentiality
and ownership of information. Who has theright to manage a child’s ‘potential’ when that
potential seems to be made evident by a genetic
screen or a brain scan? Medical lawyers andethicists need to identify the appropriate precedents for ownership of such information: forexample, is legislation around blood and tissue data held in biobanks relevant to personal
data derived from genetic screening and brainscans, or is such information more analogous
to medical records, access to which is coveredby data protection legislation in the United
Kingdom and privacy legislation about accessto health-related data in the United States.
To understand children’s capacities, and toevaluate the potential risks and benefits of theavailability of psychiatric biomarker information
to them (as well as to their families, their doctors
and other authorities), empirical research must
involve children themselves. Questionnaires
and surveys alone cannot adequately capture
children’s thought processes or their capacity formaking complex decisions. These approaches
need to be supplemented by detailed interviews
with children are required. Only then will there
be enough evidence to underpin the development of appropriate regulation for commercialorganizations, in order to maximize the benefitsof access to biomarker information for children
while effectively protecting them from harm.

Towards the future
So how might biomarkers be applied in the
future? To take one example, in the UnitedStates and the United Kingdom, there are several high-profile research programmes that seek
to identify biomarkers associated with risk ofdelinquency, antisocial behaviour or criminality in children35–37. Some of this research is
being carried out with children identified ashaving behavioural problems such as hyperactivity and impulsiveness. In other studies, theresearch subjects are children diagnosed with
conduct disorder, oppositional defiant disorderHORIZONSNATURE|Vol 460|9 July 2009or ADHD. Some researchers hope that suchstudies will establish biomarkers (for example,
brain-based markers, cardiac markers or neuroendocrine system markers) that would allow
at-risk children to be identified before they display serious behavioural problems. Children athigh risk could then be treated before symptoms
arise, to prevent the development of delinquent
behaviours. For prevention to be successful inthis high-risk group, interventions would needto take place very early, in the preschool years(ages 3 to 5)38.
The aim of this research is to develop programmes of identification and intervention
that will reduce the individual and social burdens of severe antisocial behaviour in adults.
However, we are of the view that, at present, theassumption that better understanding of theneurobiological risk of delinquency will facilitate early identification and prevention efforts
is unfounded. Certainly, carrying out earlyinterventions on the basis of this assumption
would be premature. For example, we would bevery concerned if a 4-year-old boy displaying
mild hyperactive behaviours were a candidate
for treatment with stimulant drugs based on
his hyperactivity being a predictor of futuredelinquency. Antisocial behaviour in adults
arises from a complex course of neurologicaldevelopment in certain environmental andsocial contexts39, and we do not think that there
is enough evidence that biomarkers, at least as
they are conceived and identified at present,
provide a justifiable basis for intervention programmes of this type.
Moreover, the assumption that childhood
diagnoses such as conduct disorder, oppositional
defiant disorder and ADHD represent underlying biological impairments is problematic, giventhat these diagnoses have questionable validity,
especially in the preschool population. Without
ongoing social and ethical analysis, as well as
careful thought by the researchers about theirrole in this process, the future use of psychiatricbiomarkers could marginalize efforts to identify
and address social and environmental factors
associated with the development of antisocialand criminal behaviours in young people. It
could also reinforce the use of problematic
diagnoses and/or medical treatments to manage the current and anticipated behaviour ofvery young children. Such developments could
lead to stigma and labels that affect children’s
psychological development, their social andeducational opportunities, and their medicalcare and employment options.
Clearly, the aim of developing psychiatricbiomarkers is to improve the well-being of children and of society in general. But given the
many issues that need to be considered (Fig. 2),
a comprehensive programme of researchneeds to be carried out before biomarkers canbe used ethically and effectively in the clinic,
courtroom, classroom and community. The
programme that we have outlined here can beaccomplished only through interdisciplinaryinteractions between neuroscience researchers, doctors, social scientists, ethicists, legal
scholars, policymakers and those involved incommercializing biomarkers. We do not envisage one large research programme, however.
Instead, we think that multiple smaller collaborations, built around a variety of clinical andnon-clinical sites, will be most effective.
The involvement of social researchers and ethicists at such sites should not be ad hoc. Social,
ethical and policy concerns should be integral
to the design of each study. This will also help toensure that multidisciplinary engagements arecollaborative and constructive for all researchers involved. It is unclear whether mandating
the inclusion of these concerns in all relevantscientific research programmes on biomarkers
is an effective strategy. All genomics research
programmes are required to include an ethical,
legal and social issues component, and this has
resulted in important research but has also created many problems, such as tensions among
researchers from different disciplines, and a lackof integration of social and scientific researchgoals. It is probably more effective to identify
which ethical issues are the most crucial andthen to challenge the funders of such research
programmes to encourage grant applicants(through higher ratings on proposals and direct
feedback to applicants) to integrate ethical, legal
and social issues research and the appropriate
researchers into their grant proposals.
Non-scientific sites where collaborations needto take place include communities and schoolsthat carry out early-intervention programmes
for children, juvenile prisons and courtrooms,
and corporations that commercialize biomarker information. The development of research
programmes will depend on access to thesesites. Again, funding mechanisms can be used toencourage collaborative engagements between
people working at these sites and researchers. As
research information is gathered across all sites,
workshops and conferences can be organized toshare knowledge and specifically to guide ethically informed, clinically relevant and sociallyeffective policymaking around the use of psychiatric biomarkers in children.
■© 2009 Macmillan Publishers Limited. All rights reserved

Ilina Singh and Nikolas Rose are at the BIOS
Centre, London School of Economics, Houghton
Street, London WC2A 2AE, UK.
e-mail:i.a.singh@lse.ac.uk
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