A version of this paper has been published in the Lancet Child and Adolescent Health:

Totsika, V., Liew, A., Absoud, M., Adnams, C., & Emerson, E. (2022). Mental health
problems in children with an intellectual disability. The Lancet Child and Adolescent
Health. DOI:https://doi.org/10.1016/S2352-4642(22)00067-0
Title: Mental health problems in children with intellectual disability
Authors:
Vasiliki Totsika, PhD.
Affiliations: 1. Division of Psychiatry, University College London, UK; 2. Department of
Psychiatry, Centre for Developmental Psychiatry and Psychology, Monash University,
Australia; 3. Centre for Educational Development Appraisal and Research (CEDAR),
University of Warwick, UK; 4. Tavistock & Portman NHS Foundation Trust, UK.
Address: Division of Psychiatry, UCL, Maple House, 6th Floor, 149 Tottenham Court Road,
London, W1T 7NF
Ashley Liew, MRCPsych
Affiliations: 1. National & Specialist CAMHS, South London and Maudsley NHS
Foundation Trust; 2. Evelina London Children’s Hospital, Guys and St Thomas’ NHS
Foundation Trust; 3. Centre for Educational Development Appraisal and Research (CEDAR),
University of Warwick; 4. Institute for Mental Health, University of Birmingham
Michael Absoud, PhD
Affiliations: 1. Department of Women and Children's Health, Faculty of Life Sciences and
Medicine, School of Life Course Sciences, King's College London, London, UK; 2.
Children's Neurosciences, Evelina London Children' Hospital, St Thomas' Hospital, King's
Health Partners, Academic Health Science Centre, London, UK.
Colleen Adnams, FCPaed(SA)
Affiliation: Division of Intellectual Disability, Department of Psychiatry and Mental Health,
University of Cape Town.
Address: Division: Intellectual Disability, Department of Psychiatry and Mental Health,
Room 33, E floor, Neuroscience Institute, Groote Schuur Hospital, Anzio Rd, Observatory,
7925, Cape Town, South Africa.
Eric Emerson, PhD
Affiliations: 1. Centre for Disability Research, Faculty of Health & Medicine, Lancaster
University, UK; 2. Centre for Disability Research & Policy, Faculty of Medicine and Health,
University of Sydney, NSW, Australia; 3.College of Nursing and Health Sciences, Flinders
University, Adelaide, South Australia, Australia
Address: Cleredene Vicarage Hill, Branscombe, East Devon, EX12 3DN, UK
Corresponding author:

1
Dr Vasiliki (Vaso) Totsika, Division of Psychiatry, UCL, Maple House, 6th Floor, 149
Tottenham Court Road, London, W1T 7NF, UK
Email: [email protected]
Telephone: 0044 (0) 2076799002

Summary
Intellectual disability ranks in the top ten causes of disease burden globally; and is the top
cause among under-fives. About 2-3% of children have an intellectual disability, while about
15% of children experience difficulties consistent with an intellectual disability (global
developmental delay, borderline intellectual functioning). The present review discusses the
prevalence of mental health problems, interventions to address these, and issues of access.
We take a global perspective where possible given the majority of children with intellectual
disability live in low and middle-income countries (LMICs). Approximately 40% of children
with intellectual disability present with a diagnosable mental health problem, a rate that is at
least double that in typically developing children. Most risk factors for poor mental health
and barriers to accessing support are not unique to intellectual disability. With proportional
universalism as the guiding principle for achieving reduction of mental health suffering at
scale, we discuss four directions for addressing the mental health inequalities in intellectual
disability.
Key Messages
The rate of mental health problems in children with intellectual disability is at least double
that in typically developing children both in high-income countries and in LMICs.
There are substantial gaps in the evidence currently available for effective interventions to
address the range of mental health problems in children with an intellectual disability.
Access to treatment and interventions is an issue in high-income countries and in LMICs.
Universal and selective prevention approaches to prevent or reduce mental health problems
by reducing exposure to known risk factors should actively include children with intellectual
disability.
Intellectual disability could provide an exemplar paradigm in the generation of evidence for
interventions that address differential susceptibility to mental health problems in multiply-
disadvantaged populations.
A significant first step in increasing access to low-intensity, common psychological therapies
is expediting their efficacy and effectiveness testing in intellectual disability.
The exclusion of children with intellectual disability from ongoing intervention testing and a
narrow focus on certain groups of children with intellectual disability when not scientifically-
justified are research practices that hinder the development of inclusive evidence and
evidence that is representative of the complexity in neurodevelopmental disabilities.

2
------------------------------------Insert Text Panel 1 approximately here ----------------------------

3
Introduction
Intellectual disability is a term that refers to a heterogeneous group of neurodevelopmental
conditions, primarily characterised by significant limitations in cognitive functioning and
adaptive behaviour (e.g., daily living skills, social participation, communication skills).1
Limitations need to be present in the developmental period (typically 0 to 18 years).
Cognitive or intellectual functioning has traditionally been measured through IQ tests. An IQ
of below 70-75 is recommended for a clinical diagnosis. Currently, clinical diagnosis also
requires a score of two or more standard deviations below the population norm on a
standardised measure of adaptive skills. The term intellectual disability was formalised circa
20072 to replace mental retardation, a term still used in several countries today. Both the term
and the classification of the condition have evolved in the past 15 years. The incoming
revision of the International Classification of Diseases (ICD-113) renamed ‘mental
retardation’ as disorder of intellectual development, and positions it within
neurodevelopmental disorders. ICD-11 recognises that standardised assessments may not be
possible in several LMICs, where behavioural indicators could instead identify intellectual
disability and describe its severity.4
In high-income countries, 2–3% of children have an intellectual disability.5,6 In LMICs there
is some, albeit limited, epidemiological evidence that prevalence might be higher,7,8,9 largely
due to higher incidence resulting from increased exposure to several well-established risk
factors for intellectual disability, such as undernutrition, low levels of home stimulation, and
infections.10 In addition to classification by severity level (mild, moderate, severe, profound),
cause of intellectual disability often distinguishes cases into genetic (linked to an identified
genetic or chromosomal anomaly, e.g., Down Syndrome, Fragile X) and non-genetic (no
known genetic cause). Genetic syndromes are more likely in children with severe or profound
intellectual disability. Intellectual disability can also be characterised as syndromic and non-
syndromic.
Up to the age of 5 years, when standardised assessment is less reliable, children are more
likely to be assigned a diagnosis of (global) developmental delay. There are no robust
epidemiological data on the prevalence of global developmental delay, though it is
considered to affect about 1% to 3% of under-fives in high-income countries.11 A related
condition is Borderline Intellectual Functioning (BIF). People whose cognitive functioning
falls one standard deviation below the population mean (i.e., an IQ score of approximately 70
to 85) are at risk of BIF; a condition not included in current diagnostic systems as a separate
diagnostic entity but considered a health meta-condition.12 BIF affects about 11% to 13% of
the population in high-income countries.12 In childhood, these children are mostly thought of
as slow learners and BIF is not identified as a separate condition. While BIF is no longer part
of intellectual disability diagnostic codes, the profile of mental health needs in this group
resembles that of intellectual disability, warranting consideration in the present review.
Comorbid neurodevelopmental disorders in children with intellectual disability
Notwithstanding the difficulties diagnosing additional neurodevelopmental disorders in
intellectual disability, especially at the more severe levels, autism and Attention-Deficit
Hyperactivity Disorder (ADHD) are highly prevalent in intellectual disability.

4
Among children with an intellectual disability about 18% are estimated to also have autism,
and this is increasing over time due to the increasing identification of autism overall.13
Autism is significantly more likely in genetic syndromes: 61% in females with Rett
syndrome, 54% in Cohen’s syndrome, and over 20% in Fragile X, Tuberous Sclerosis,
Cornelia de Lange, Angelman’s and CHARGE syndromes.14 Within autism, intellectual
disability prevalence is 33%,15 while BIF is present in 25% of autistic children.16
ADHD is present in approximately 39% of children with intellectual disability,17 while 6·9%
of all people with ADHD also have intellectual disability.18 ADHD is more likely in genetic
syndromes associated with intellectual disability (e.g., in over 50% of boys with Fragile X
syndrome and 65% of children with Williams syndrome).19
The strong genetic links between intellectual disability, ADHD and autism point to shared
genetic causes across neurodevelopmental conditions, while the less strong genetic links
between these neurodevelopmental disorders and overall mental health problems in
intellectual disability suggest that environmental risk accounts for a large part of the variance
in mental health problems seen in children with neurodevelopmental conditions.20
Social and environment risks and intellectual disability
Social and environmental adversity and factors related to that (e.g., antenatal substance
misuse, maternal health and mental health problems, environmental pollution) are well-
established causes of (non-genetic) intellectual disability and undoubtedly contribute to many
of the inequalities faced by people with intellectual disability in terms of life expectancy and
mortality, physical and mental health.21,22 Similarly to typically developing children, socio-
economic adversity in the form of income poverty, material hardship and living in a deprived
neighbourhood are risk factors for mental health problems in children with intellectual
disability. Maternal mental health problems, harsh/adversarial parenting or inconsistent
parenting also contribute to mental health problems in children with intellectual disability.23,24
Diagnosing mental health disorders in children with intellectual disability
When considering the prevalence of specific mental health disorders, it is worth bearing in
mind that clinical diagnoses in this population represent a challenge compared to typically
developing children. Limited communication skills and/or cognitive limitations may render
self-report difficult (or perceived to be unreliable). ‘Diagnostic over-shadowing’ – the
attribution of a mental health symptom to the intellectual disability – further hinders the
recognition of mental health problems. Co-occurring conditions such as autism may also
contribute to diagnostic overshadowing, for example the attribution of social withdrawal to
autism rather than underlying depression. Additionally, the phenomenology of mental health
symptoms differs in people with more severe intellectual disability, and adapted diagnostic
manuals have been developed to assist clinicians (e.g., Diagnostic Manual Intellectual
Disability; DM-ID-225). Siegel et al 26 recently published practice guidelines for the
assessment of mental health problems in children with intellectual disability.
Prevalence of mental health problems in children with intellectual disability
Approximately 40% of children and adolescents with an intellectual disability present with a
mental health problem, either diagnosed or at diagnosable levels. The evidence arising from
systematic reviews and meta-analyses in the past 10 years is consistent: 30% to 50% in

5
Enfield et al.27 and 38% to 49% in Buckley et al.17 When compared to typically developing
children, levels of mental health problems are always significantly higher in intellectual
disability. 27
The worldwide prevalence of mental health problems in children and adolescents is
approximately 13%.28,29 Recent rates from the US and UK of – epidemiologically defined –
mental health problems suggested that prevalence might be higher at 16% (i.e., 1 child in
every 6). 30 With a prevalence of 40% in intellectual disability, 2 in every 5 children with
intellectual disability will present with a mental health problem; the prevalence of mental
health problems in children with intellectual disability is at least double that in the overall
child population.
Psychiatric symptoms across neurogenetic syndromes are much higher, ranging between 32%
and 74%, with substantial variation seen at syndrome-level (lower rates in Down syndrome,
higher rates in Prader Willi).31 Current meta-analytic evidence reports no association with
severity of intellectual disability.17,27 However, severity is not defined in a consistent manner
across studies (some studies used IQ levels, some clinical classifications or other criteria),
and emerging evidence suggests there may be a strong association with severity of limitations
in adaptive skills (e.g., social skills 31).
Between 80% and 90% of studies included in systematic reviews of prevalence of mental
health problems are from high-income countries. Therefore, the prevalence estimates reported
above cannot be generalised to LMICs. In the absence of comparable evidence, the Multiple
Cluster Indicators Surveys (MICS) by UNICEF provide a unique opportunity to derive such
estimates, including for children at risk of intellectual disability.8 Figure 1 shows age- and
gender-adjusted Prevalence Rate Ratios (APRRs with 95% CI) for emotional problems
(parent report of child showing on a daily basis signs of depression or anxiety) in children at
risk of intellectual disability across 39 LMICs (286,943 5–17 year-old children). The overall
APRR is 3·14 (95% CI: 2·42, 4·08, p<0.001), suggesting that emotional problems are two to
four times more likely in children with intellectual disability compared to their non-disabled
peers.
Therefore, despite the vastly different definitions of intellectual disability and mental health
problems between robust meta-analyses from high-income countries and epidemiological
estimates from LMICs, there is a convergence in estimates where, again, rates are at least
double compared to children without intellectual disability. However intellectual disability is
defined, rates of mental health problems are consistently higher in intellectual disability.
Many of the children who will require mental health services will not necessarily be
diagnosed as having an intellectual disability, especially in countries where specialist
diagnostic services or universal developmental surveillance are not available.
-----------------------------Insert Figure 1 approximately here---------------------------------
Emotional disorders
Latest meta-analytic estimates indicate that about 5% of children with intellectual disability
present with any anxiety disorder, with rates higher in adolescence (7·9%).33 For comparison,
the worldwide prevalence of any anxiety disorder is 6·5% in childhood. 28 Some reviews in
intellectual disability report higher rates (10–17%) of anxiety in intellectual disability, though
these tend to include a smaller number of studies. 34 Specific phobias are the most frequent

6
anxiety disorders. In genetic syndromes, anxiety symptoms are higher; half of children with
Williams syndrome will present with any anxiety disorder (between 48% and 58%).31,35
Specific phobias (e.g., noise, blood/injury/injection, animals) and generalised anxiety
disorders are the two most prevalent disorders in Williams syndrome with rates of 39% and
10%, respectively.35 Similarly, 43% of children with 22q11.2 deletion score in the clinical
range for anxious/depressed.31
Meta-analytic evidence from autism studies suggests that anxiety symptoms tend to be more
prevalent among autistic children with an IQ in the BIF range, whereas those with an IQ that
places them in the intellectual disability range tend to score significantly lower on anxiety
symptoms.36,37 This is not necessarily the case for specific sub-types of anxiety such as
obsessive compulsive disorder or separation anxiety. The question as to whether anxiety is
higher or lower among autistic children with and without an intellectual disability is
complicated by issues of measurement (i.e., symptoms versus diagnosable disorder), type of
anxiety, and method of intellectual disability ascertainment (only IQ scores versus clinical
diagnosis).
Depressive disorder (any) is present in approximately 2·8% of children and adolescents with
intellectual disability, with dysthymic disorder and major depressive disorder present in 2·8%
and 3·4% of children, respectively. 33 For comparison, the worldwide prevalence of
depressive disorder is estimated at 2·6% but major depressive disorder is seen in 1·3% of
children. 28 There is no robust evidence yet of prevalence increases in adolescents with
intellectual disability, but an earlier diagnosis of affective disorder (before puberty) increases
the risk for rapid cycling bipolar disorder.38 Diagnosing depression in this population can be
challenging, in particular when communication difficulties and more severe cognitive
impairment are present. However, for unipolar depression at least, there is a suggestion that it
presents at similar rates in severe intellectual disability (compared to milder levels ),39 with
anhedonia and depressed mood the most reliable behavioural indicators of depression in
severe intellectual disability.40 Anxious/depressed symptoms are highly prevalent in Williams
syndrome, 22q11.2 deletion, and Prader Willi (41%, 58% and 71%, respectively).31 Similar to
anxiety, there is some, albeit limited, evidence that rates of depressive disorders are lower in
autism combined with intellectual disability (or low IQ) compared to autism alone.41
Meta-analytic evidence on the prevalence of all other disorders, i.e., other than emotional, is
more limited, mostly because primary studies in these areas are very few. Below we review
any evidence available from systematic reviews and/or population studies.
Behavioural disorders
Here, we consider both disruptive disorders and challenging behaviours: the latter term refers
to behaviours that pose a significant risk to the individual or others. As a term, it is not a
diagnostic code, though services do use the term to describe need and plan interventions.
Oppositional Defiant Disorder (ODD) is present in approximately 12% of children with
intellectual disability 34 (3·6% is the worldwide prevalence for comparison 28). Symptoms
used in the evaluation of ODD in typical development (e.g., often angry and resentful, refuses
to comply with requests) are valid on the whole in intellectual disability.42 Conduct disorder
rates (3·6% worldwide prevalence 31) are present in 5% of children with intellectual
disability. 34 When considering diagnosable symptoms rather than disorders, epidemiological
evidence from Australia and UK has shown that between a quarter to half of all children with

7
intellectual disability present conduct problems at clinically ‘abnormal’ or ‘borderline and
abnormal’ levels.43,44 Conduct problems are present at similar levels for children with BIF,
43,45
but tend to be much higher (between 58% and 65%) when children with intellectual
disability also present with autism.44
Self-injurious behaviour, aggression and destructive behaviours occur frequently in
intellectual disability. In a study across nine European countries and the US of people with
intellectual disability aged 2 to 91 years old, 1122 out of 1335 presented at least one
behaviour deemed to be challenging, with head hitting, hitting, pushing, pulling or grabbing
others, destroying things and yelling and screaming present in over 30% of cases. 46
Systematic reviews in specific syndromes suggest that aggression is present in 36% of people
with Fragile X, self-injury is present in 49% of people with Fragile X syndrome and between
25% and 62% of people with Cornelia de Lange. 47,48 Self-injurious behaviour is likely
present at similar levels between children with autism only (42%) compared to both autism
and intellectual disability, though hair pulling and self-scratching are more frequent when the
child also has an intellectual disability.49
Behavioural disorders increase the burden of care for parents and families and are usually the
main reason for contact with health care services. Challenging behaviours tend to have a
communicative function, i.e, they may substitute for the poorer communication skills in
intellectual disability, although their causes are many and varied. They are associated with
mental health problems (e.g., depression 40) though should not be misrepresented as an
atypical mental health presentation but their presence should alert to the need for a more
detailed mental health investigation. Similarly, challenging behaviours are associated with
physical health problems or chronic health conditions (reflux, pain, visual impairment,
incontinence 50), and again, where present, challenging behaviours signal the need for a
detailed physical investigation.
Eating Disorders
Meta-analytic data on eating disorders in intellectual disability are not readily available, with
a single epidemiological study in the UK indicating a prevalence of 0·2%. 21
Trauma Disorders
Post-Traumatic Stress Disorder is thought to present in 0·2–2·5% of children with intellectual
disability, and symptoms include disruptive/agitated behaviour indicative of fear while
repetitive play may indicate re-experiencing or re-enactment. 21,51 The prevalence of
developmental trauma or Complex Post-Traumatic Stress Disorder 3 among children with
intellectual disability is not known, though adverse childhood experiences are more likely in
children with intellectual disability compared to typical development, 21 including physical,
sexual and emotional abuse 52 which in turn have been linked to post-traumatic stress in
intellectual disability.53,54
Psychosis
In a total population study of about half a million children, the prevalence of psychotic
disorder in intellectual disability was 4·2% (compared to 1·1% in children without
intellectual disability), while among children whose mother had schizophrenia 24·4% of
children with intellectual disability also developed psychotic disorder (compared to 6·5% of

8
children without intellectual disability). 55 Among children with early-onset schizophrenia, a
large proportion are thought to have neurodevelopmental disabilities, and there is substantial
comorbidity between intellectual disability and schizophrenia (across the lifespan 56),
especially with 22q11.2 deletion syndrome where about 30% of those affected will present
with schizophrenia.57 Shared genetic pathways between intellectual disability (and other
neurodevelopmental disorders) and schizophrenia 58 support the need to consider intellectual
disability in adolescents or children presenting with psychotic symptoms.
Suicide and self-harm
Suicidality is present in approximately 20% of children with intellectual disability 59,60 and
the idea that intellectual disability somehow protects from suicidality is being challenged. 59
In a large study of young people with Prader Willi syndrome, suicidal ideation was seen in
7·7% of children while suicide attempts were present in 2·9% of young people (over the age
of 13) with Prader Willi. 61 Suicidal talk is present in 20% of autistic children and adolescents
with an IQ below 70 and 15% in those with BIF. 62
------------------------------------Insert Text Panel 2 approximately here ----------------------------
Treatments and interventions for mental health problems in children with intellectual
disability
Two treatment approaches for behavioural disorders have an established evidence-base: (1)
personalised interventions based on applied behaviour analysis (ABA) and (2) parent training
(group parenting programmes based on behaviour analytic and social learning theory
principles). The first approach typically involves assessing the reason a specific behaviour is
presented (e.g., head banging may serve the function of avoiding or escaping from aversive
interactions with carers) and then developing a plan to reduce this behaviour through a
combination of options that target changes in what happens in the person’s environment
before and after the behaviour, with parallel skills development to enable the person to
communicate their needs. As an overall approach, these personalised ABA treatments lead to
large reductions in overall challenging behaviour and also specific behaviours, such as self-
injury or phobias. 65-68 Some of their individual components are also highly effective: using
alternative communication, 69 reinforcement and alternative reinforcement, 68,70 and giving
people choice71. Choice can reduce challenging behaviour by one standard deviation, robustly
across settings, tasks, type of choice exercised, age of the person and type of disability.71
Group parent training for parents of children with developmental disabilities (including
intellectual disability) reduces behaviour problems by about one third of a standard deviation
74
with specific manualised and/or disability-adapted parenting training programmes (e.g.,
Incredible Years, Stepping Stones Triple P) producing larger reductions in behaviour
problems (about half a standard deviation).72-74 These treatments also lead to changes in
parenting skills and parental confidence to manage their children’s behavioural disorders.
Psychological therapies, i.e., therapies that may incorporate behavioural components but also
extend beyond them or totally based on other components (e.g., cognitive, social, systemic,
psychodynamic) have some –albeit limited– evidence that they can be effective with children
and young people with intellectual disability, especially when therapy is provided
individually.75 Currently, the evidence extends to Cognitive Behaviour Therapy (CBT) for
anger/aggression, and possibly depression although the evidence is drawn mostly from adults

9
with intellectual disability.75 Some other psychological therapies are feasible and have
attracted research interest, but they are not yet evidence-based practice (e.g., Eye Movement
Desensitization and Reprocessing for trauma, CBT for trauma; mindfulness for
aggression/anger; psychodynamic psychotherapy; animal-assisted therapy).75-79 The very
limited evidence base for psychological therapies for mental health problems with children
with intellectual disability (especially those with more severe disabilities 80) is mostly due to
lack of research in this area.
Physical exercise and occupational therapy have received some attention as mental health
treatments. Occupational therapy approaches, including multisensory environments, have a
very poor evidence base and the evidence is inconclusive. 81,82 Physical activity may bring
about some changes in behavioural disorders,83 but change in specific mental health
symptoms (anxiety/depression) does not appear to be significant,84 unless mental health is
defined more broadly as psychosocial health.85
For pharmacological treatments, the two most evidence-based areas are (1) methylphenidate
for ADHD symptoms 86,87 and (2) atypical antipsychotics or more accurately dopamine
antagonists like risperidone and aripiprazole for behavioural disorders.88-90 Methylphenidate
has been associated with large effect sizes for both hyperactivity and inattention across the
spectrum of intellectual disability severity, at least in the short-term.86,87 For behavioural
disorders, both risperidone and aripiprazole produce moderate effect sizes compared to
placebo, at least in the short-term.88-90 Both are generally well tolerated though side effects
are significant (in particular weight gain and somnolence), and likely more significant in this
population than in typically developing children. Aripiprazole may be preferred because it
appears to cause less weight gain compared to risperidone.91 Risperidone and amphetamines
have also been studied as treatments for ADHD in intellectual disability and, on the basis of
the current lack of robust evidence, are not recommended.92,93 Other pharmacological
treatments (olanzapine; beta-blockers for behavioural disorders; anti-depressants for
depression; benzodiazepines for any outcome) have no evidence or are not
recommended.91,94-96 Some agents may even cause paradoxical effects (e.g. benzodiazepines
causing disinhibition).
Current effort in evidence building does not appear to prioritise the mental health of children
with an intellectual disability: as an illustration, among 197 active studies in intellectual
disability registered in clinicaltrials.org, just 14 have mental health or behavioural disorders
as their primary outcome (see Table 1). Of these, just 10 are randomised controlled trials
(RCTs), including nine pharmacological treatments, and one parent training programme.
There are no RCTs of psychological therapies. Single syndromes appear to be favoured
currently rather than cross-syndrome or overall intellectual disability research (Table 1).
-------------------------------Insert Table 1 about here----------------------------------------------
The contribution of LMICs in the generation of evidence for intervention is in the minority,.
98,99
Parent training and parent psychoeducation are feasible in LMICs and likely effective for
reducing behavioural disorders in children with intellectual disability.98 Most interventions
tested in LMICs are adapted from high-income countries and cultural adaptations are critical
to treatment effectiveness, in particular language, cultural specificity of materials and
parents’ beliefs prior to the therapy.99 Other types of treatments such as personalised ABA
treatments have not been tested in LMICs at all. 98 Most evidence-based approaches reviewed

10
above require significant resources (specialist staff, universal screening systems, specialist
diagnostic services, early intervention services) that are not available in several LMICs.29 In
recognition of these competing factors, the World Health Organisation is currently testing an
early intervention model appropriate for low resource settings (WHO Caregiver Skills
Training for Developmental Disorders or Delays),100 with initial data indicating acceptability
and positive effects on child development, albeit no evidence is yet available for child
challenging behaviours (which represent only a small component of the intervention’s core
content). 101
Access to treatments and therapies for children with intellectual disabilities and mental
health problems.
Access to therapies and treatments is not a problem just for LMICs, it is a problem for most
high-income countries as well. Despite the fact many high-income countries have resources
and services that align well with the evidence base, there is a large gap between population
need and service access. For example, in the UK, the National Health Institute for Excellence
(NICE) guidelines for mental health problems and challenging behaviour in intellectual
disability advocate for specialist mental health services to address the complex needs of
children with intellectual disability and mental health problems; for parent training as the
main prevention tool for children at risk of mental health problems; for personalised
behavioural treatments as the first line intervention followed by antipsychotic medication if
needed. These guidelines align with the evidence currently available. However, UK
population representative data have shown that only 1 in 3 children with an intellectual
disability and a mental health problem actually access specialist mental health services.102
This is the case for other high-income countries (e.g., the U.S.103), suggesting that the mental
health needs of children with intellectual disabilities are not being met even in countries with
evidence-based service guidelines. With 0.1 psychiatrists per 100,000 children in LMICs,29
the level of unmet need will be far higher.
Frequent barriers to service access are the lack or adequacy of specialist services, stigma and
perceived stigma, poverty and social exclusion (e.g., low education).104-106 These barriers are
not unique to intellectual disability or LMICs; they are repeated across conditions and
countries though in LMICs barriers are likely more pronounced. LMICs experience
additional gaps in diagnosis and identification of intellectual disability. Where proposed
solutions have as their starting point improvement in diagnosis and identification systems,
e.g.,105
LMICs will always fall behind because of reduced resources. At the same time, a
growth in specialist mental health provision is unlikely to resolve the problem because: (a)
this approach is simply not possible in many LMICs that do not have the resources, (b) the
level of need across the population is such that even high-income countries will struggle with
rising costs, 107 and (c) this approach will always stumble on stigma– a major barrier in all
countries– and poverty, as many countries do not have universal health insurance systems.
The further development of evidence-based interventions for children with an intellectual
disability and metal health problems is much needed, but at the moment this effort has stalled
even in high-income countries, cf.80 with evidence of a selection bias that results in excluding
those with intellectual disabilities from ongoing research.108 Even if specialist interventions
were available, unless they can reach a big part of the population, they are unlikely to create a
sizeable reduction in mental health suffering in this group of children.

11
Future Directions
The wide difference in levels of mental health problems in children with intellectual
disability is unjust and at least partly preventable. Children with intellectual disability and
mental health problems are first and foremost children. They will come into contact with
primary care and community healthcare providers before any specialist input. The majority of
risk factors in this group of children are risk factors for mental health problems in all
children. Proportionate universalism 109 (Marmot) should be a guiding principle in the effort
to achieve reduction of mental health problems at scale in this population, as well as evidence
of mechanisms that sustain the large mental health inequalities seen in intellectual disability
(primarily differential exposure to risk, differential susceptibility to that risk and differential
access to effective healthcare when ill 110). 111
Universal and selective prevention models that do not exclude children with an intellectual
disability can address mental health inequalities by equalising exposure to well known risk
factors.111 Evidence across the population has shown that universal and selective prevention
models produce small but significant reduction in distress, anxiety symptoms, affective
symptoms, conduct problems and externalising problems.112 Where such approaches are
inclusive (or at least they do not actively exclude children with an intellectual disability),
there is evidence of equal benefit: for example, we found comparable effect sizes from
selective prevention (evidence-based parenting programmes not adapted for disability) on
child emotional and behaviour problems in families where the child has a disability compared
to others, 113 albeit reduced effectiveness at longer-term follow-up highlights the need for
more intense input for this group (i.e., proportionate universalism 109).
Universal and selective prevention is also effective for enhancing social skills in children
with intellectual (and other) disabilities 114 as an additional, and crucial, step in preventing
mental health problems. Universal and selective prevention is implementable and feasible in
LMICs, avoids reliance on the availability of diagnostic and specialist mental health services,
and could reduce the impact of stigma on help-seeking behaviours, by not requiring children
to be diagnosed with an intellectual disability before receiving support. 100,101,115
We need to increase our understanding of differential susceptibility to mental health problems
in intellectual disability,110 and this understanding may also be facilitated by research in other
disadvantaged groups, as disability currently appears not to be a priority in research on
equitable mental health. 106 On the other hand, the generation of evidence on what works to
address differential susceptibility would benefit from a paradigm shift; identifying
interventions that effectively enhance the capabilities of children with an intellectual
disability – as an exemplar of multiply disadvantaged children – to address the negative effect
of risk factors and applying this knowledge to other vulnerable groups of children as well.
Specialist policies, specialist services and specialist training of practitioners might intend to
meet the needs of those most in need, but evidence has repeatedly demonstrated that they
create access barriers for the majority. Specialist services are still vital of course and should
be reserved for the most complex cases.111 At this level, there are two areas of significant
need.
The first is addressing the inequality of establishing the effectiveness of common
psychological therapies for common psychological problems such as anxiety or depression.

12
The dearth of evidence in intellectual disability (see above and Table 1) contrasts with the
expanding evidence base in autism research and the established evidence in childhood
anxiety research.116,117 The exclusion of children with intellectual disability from the
development of the evidence-base for common psychological therapies is unhelpful and
discriminatory. Adaptations needed for making CBT more accessible are known.118 Efficacy
testing needs to be expedited, so that children with intellectual disability can benefit from
efforts to increase access to common psychological therapies similarly to other children.
Low-intensity therapy provided by non-specialist staff is effective in intellectual disability,
and holds promise for LMICs.98
The second area of need is integrating complexity in the generation of evidence for specialist
interventions and treatments. A significant number of children with intellectual disability will
present with more than one neurodevelopmental condition. An increasing number of children
are identified with syndromic intellectual disability and have additional physical health
problems and high levels of mental health needs. A significant minority presents with severe
or profound limitations and complex physical health issues. These children are not able to
have their mental health needs met through the existing evidence,80 leaving specialist services
to make decisions on very poor quality evidence or evidence of unknown relevance to this
population. Two major stumbling blocks in developing an evidence base for specialist
interventions for these children are (1) the application of many exclusion criteria in the
generation of evidence and (2) a narrow focus on a very specific sub-population (e.g., one
genetic syndrome - see Table 1 for example). A crucial question is whether the decision to
exclude children with intellectual disability from general child mental health trials or the
decision to test a mental health intervention with only one group of children with intellectual
disability and not others are practices justified by the science or are being driven by other
factors (e.g., funding preference, publication bias towards high effect sizes). While, in some
cases, the exclusion of children with intellectual disability may have a strong scientific basis
(for example, evaluating a talking therapy that requires higher-order cognitive functions),
there is a question on whether reasonable adjustments could support their inclusion.
Likewise, a narrow focus on one genetic neurodevelopmental syndrome may be justified to
understand the genotype-phenotype correlation and develop specific molecular targeted
treatments. Mental health treatments for specific neurodevelopmental conditions, however,
may have broader utility given converging pathways across conditions. Hence, evaluating
condition-specific therapies should not preclude studies that test broader utility early on in
intervention programmes. At the level of evidence-base development for specialist mental
health interventions, funders need to query more closely the study recruitment criteria and be
satisfied that exclusion criteria are as scientifically sound as inclusion criteria. There is a
drive for more pragmatic trials to generate evidence relevant to multi-morbidity, and also a
drive to move away from specific disorders to neurodevelopmental disorder as an overall
group (for example, the recent change in Scottish Government guidelines for a
neurodevelopmental service). Both these shifts have the potential for a level change in
meeting the mental health needs of children with an intellectual disability. There might be
scepticism regarding the application of these approaches, but what is clear at the moment is
that prevalence of mental health problems in intellectual disability is very high, the available
evidence on what works is limited, and it is questionable whether needs are being met.
---------------------------------------Insert Text Panel 3 approximately here----------------------

13
Conclusions
Approximately 40% of children with an intellectual disability have a diagnosable mental
health problem. The rate of mental health problems in children with intellectual disability is
at least double that in typical development and this is the case in both high-income countries
and LMICs. Evidence-based treatments are available for ADHD and behavioural disorders.
The evidence for interventions for other types of mental health problems and for the
effectiveness of common psychological therapies is limited. The level of unmet need in the
population is high and likely higher in LMICs. Current efforts to generate evidence are
unlikely to meet the mental health needs of these children. It is time to advocate for a
paradigm shift, involving a tiered approach where public health services do not exclude
children with intellectual disability while the generation of evidence for universal and
secondary prevention champions this group as an exemplar for evidence generation for all
children; low intensity psychological and behavioural therapies become more accessible; and
barriers to developing robust evidence for specialist mental health supports are reduced.

14
Text Panel 1: Search Strategy and Selection Criteria
We searched electronic databases (Medline, PsychInfo, Embase, Web of Science and
Cochrane Library) using terms related to the relevant Population (learning disab* OR
learning difficult* OR learning impair* OR intellectual* disab* OR intellectual* impair* OR
borderline intellectual* OR development* disab* OR development* disorder* OR
developmental delay OR development* impair* OR intellectual developmental disorder OR
mental* deficien* OR mental* retard* OR mental* handicap* OR mental* disab* OR
mental* impair* OR mental* challenged OR subaverage intelligence OR subnormal OR
cognitive delay OR autis* or ASD or Asperg* or Autism Spectrum Disorders or Down*
Syndrome or trisomy 21 or Smith-Magenis or Rett or Lesch-Nyhan or Prader-Willi or
Angelman or fragile X or Cri-du-chat or Cornelia de Lange or de Lange or Rubinstein-Taybi)
and Outcome (mental health or mental disorder or depress* or mood disorder or affective
disorder or low affect or flat affect or dysthym* or emotional disord* or anxiety disorder or
anx* or phobi* or feeding disorder or post-traumatic or conduct disorder OR challenging
behavi* or maladaptive behavi* or aberrant behavi* or aggress* or SIB or stereotyp* or self-
injur* or ruminat*), restricting the search to systematic reviews and meta-analyses (as
identified in the title), children and young people. Terms were combined using AND, and in
Medline MeSH terms were also used. No time restriction was imposed, but we only searched
papers published in the English language. The search resulted in 11,627 papers. When
duplicates were removed, 10,410 papers were retained for screening. Searches were
supplemented by hand searching the reference lists of relevant publications identified by the
electronic searches. We prioritised evidence from meta-analyses that included systematic
reviews that had applied robust criteria on study selection (population-based studies, clinical
diagnosis) where available. Where no evidence from systematic reviews was available, we
drew on evidence from population-based studies (for questions regarding prevalence) or
randomised controlled trials (for questions regarding intervention effectiveness). We
considered any papers relevant to children with an intellectual disability (with or without co-
presenting neurodevelopmental conditions [e.g., autism, ADHD]), borderline intellectual
functioning or (global) developmental delay. Papers presenting evidence on children with
autism or ADHD without intellectual disability or children with broadly-defined
developmental disabilities were not considered.

15
Text Panel 2: Strengths and limitations of the evidence on prevalence of mental health
problems in children with intellectual disability
Systematic reviews and meta-analyses considered tended to include primary studies reporting
on both clinical diagnoses and standardised measures of mental health symptoms. The
relative diversity in the operationalisation of mental health problems in systematic reviews in
intellectual disability reflects the well-known difficulties in establishing valid clinical
diagnoses in intellectual disability. While clinical diagnoses rates would be more
conservative than symptom rates, two points are worth highlighting: (a) clinical diagnoses in
primary studies are not always based on intellectual disability-adapted diagnostic criteria, c.f.
33
and (b) variation in prevalence can be seen at symptom-level too depending on whether the
measure was developed specifically for this population or not.17,63 The evidence on
prevalence of overall mental health problems in children with intellectual disability from two
separate systematic reviews that screened primary studies on sample representativeness and
size is consistent between reviews from separate teams.27,17 These findings are also in
agreement with another recent systematic review that included individuals with intellectual
disability aged 12 years and older.64 The consistency in findings across different teams and
inclusion criteria in these reviews lends confidence that notwithstanding variation in primary
study quality this is our best current estimate of overall rates of mental health problems in
intellectual disability. Two reviews provide meta-analysed overall prevalence estimates.17,64
Meta-analysed prevalence data are even less available for specific mental health disorders,
such as eating disorders, PTSD, CPTSD, psychosis, either because not enough primary
studies are available,e.g., 51 or no systematic review data are available for children with
intellectual disability, and this is also the case for behavioural disorders or challenging
behaviours in childhood. Available systematic reviews either include primary studies
published over 10 years ago 34 or identify significant heterogeneity, questionable external and
internal validity as well as sampling biases in primary prevalence studies. 33 Reviews of
genetic syndromes tend to operationalise mental health at the level of symptomatology and
either focus on one syndrome,35 one mental health problem35 or any mental health symptom
across syndromes depending on the availability of primary data.31 Reviews of mental health
problem prevalence in autism are more numerous but, within those, intellectual disability,
when considered, is defined by IQ level 36,37 while the issues with the validity of
measurement are still present. 63 Between 80% and 90% of studies in reviews of mental
health problem prevalence in intellectual disability are from Europe and the US, while LMIC
participation is very limited. Limitations in the existing evidence on prevalence call for more
primary research focused in childhood, including robust population studies on specific mental
health disorders and symptoms, validity of diagnostic approaches and standardised measures
for children with intellectual disability.

16
Text Panel 3: Future Directions – Summary recommendations
Universal and selective prevention
The reduction of mental health problems at scale among children with intellectual disability
requires a shift in focus towards public health approaches.
Universal models for mental health problem prevention should be inclusive of children with
intellectual disability: most social risk factors for poor mental health are not unique to
intellectual disability.
Selective prevention that targets social skill development among all children with or at risk of
disability can have direct and indirect benefits for children with intellectual disability.
To address mental health inequalities in intellectual disability, epidemiological research is
needed to describe mechanisms of differential susceptibility: evidence from other disabled
groups where available could be transferrable to intellectual disability; but to test the
effectiveness of selective prevention on vulnerable population groups, intellectual disability
should be studied as the exemplar multiply-disadvantaged population.
Universal and selective prevention is implementable and feasible in LMICs, and avoids many
known barriers to accessing support.
Specialist treatment and interventions
Investment in specialist services and interventions needs to acknowledge access will not be
easy for most children, either in LMICs or high-income countries.
Common psychological therapies for common mental health problems need to be tested with
children with intellectual disability, as they are for other groups of children.
We need to incorporate complexity in the building of evidence for specialist mental health
interventions. This requires both a narrow focus on describing phenotype in specific sub-
groups (e.g., one genetic syndrome) and a more inclusive stance during mental health
intervention testing.

17
Contributors
VT: Conceptualisation, Methodology, Formal Analysis, Writing-original draft, writing-
review and editing
AL: Conceptualisation, Methodology, Writing-review and editing
MA: Conceptualisation, Methodology, Writing-review and editing
CA: Conceptualisation, Methodology, Writing-review and editing
EE: Conceptualisation, Methodology, Formal Analysis, writing- review and editing

Declaration of Interests
AL received personal speaking and travel honoraria from Flynn Pharma, Takeda and
Livanova. All honoraria were not related to the present review. The other authors declared no
conflicts of interest.

18
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 60.00

50.00

40.00

30.00

20.00

10.00

0.00
Serbia

Suriname
Costa Rica
Malawi

Zimbabwe

Honduras

Algeria
Belarus

Montenegro

Madagascar
Kyrgyz Republic
Bangladesh

Georgia

Cuba
Iraq

Kiribati

Tuvalu

Pooled estimate
Nepal

DR Congo
Guyana

Ghana
Tonga
Samoa
Central African Republic

The Gambia
Kosovo
Lesotho

Tunisia

Guinea-Bissau

Sierra Leone
Mongolia

Dominican Republic

Togo

Sao Tome & Principe

Chad
Argentina

Palestine
Turkmenistan

North Macedonia

Figure 1 Age and Gender Adjusted Prevalence Rate Ratios (with 95% CI) of emotional
problems in children with intellectual disability across 39 low- and middle-income countries.
Intellectual disability status and emotional problems were determined by responses to the
Washington Group for Disability Statistics’ module on functional difficulties.32 All analyses
are weighted using UNICEF calculated sample weights to estimate national prevalence rates
with standard errors adjusted to take account of the clustered sampling strategies used. The
overall APRR was derived from mixed effects multilevel modelling with random-effects
specified to allow both the intercept and slope of the association between intellectual
disability and emotional difficulties to vary between countries. Thirty of 39 APRRS were
significantly larger than 1. Associations between country wealth (per capita Gross National
Income [Atlas Method] and prevalence or APRR were not significant. Data Source: UNICEF
MICS Round 6 surveys, 2017-2020, 39 surveys, N=286,943 children aged 5-17

28
Table 1 Current clinical trials on intellectual disability (data from clinicaltrials.gov search 16.11.2021) with a main focus on child mental health*
Trial number Study Title Target population Target N Study is Primary outcome Country
RCT
NCT02914951 Cognitive-Behavioral Therapy for ASD+IQ 55-85 (8-16 6 No aggression, irritability USA
Irritability in Children With yrs) and ABC-I**≥15
Autism Spectrum Disorder
and Intellectual Disability
NCT04821856 Evaluation of the Effectiveness of Intellectual disability 140 Yes irritability Australia
Cannabidiol in Treating Severe (6-18 yrs) and ABC-I
Behavioural Problems in Children ≥18
and Adolescents With Intellectual
Disability
NCT04529226 Study to Compare Clozapine vs Intellectual disability 114 Yes schizophrenia Spain
Treatment as Usual in People (16-40 yrs) and
With Intellectual Disability & treatment resistant
Treatment-resistant Psychosis psychosis
NCT03086876 Evaluation of Parent Intervention Moderate-Severe 258 Yes challenging behaviour UK
for Challenging Behaviour in intellectual disability total score
Children With Intellectual (30 -59 months )
Disabilities (EPICC-ID)
NCT03862950 A Double-Blind, Placebo- Fragile X (6-35 yrs) 120 Yes challenging behaviour Canada
Controlled Trial of Metformin in and age equivalent total score
Individuals With Fragile X higher than 13 or IQ
Syndrome (FXS) higher than 85 on the
Leiter-III)

29
NCT05120505 Metformin in Children With Fragile X (2-16 yrs) 20 Yes challenging behaviour China
Fragile X Syndrome total score
NCT04977986 A Randomized, Double-Blind, Fragile X (3-18 yrs) 204 Yes irritability USA,
Placebo-Controlled Multiple- Australia,
Center, Efficacy and Safety Study Ireland,
of ZYN002 Administered as a UK
Transdermal Gel to Children and
Adolescents With Fragile X
Syndrome - RECONNECT
NCT04526379 Communication in Prader-Willi Prader Willi (9-12 60 (but No emotional control France
Syndrome: Study of Emotional yrs) intervention
Control Related to Behavioral n:12)
Disorders, Their Daily
Repercussions and Examination
of an Innovative Therapy:
Transcutaneous Electrical Nerve
Stimulation of the Vagus Nerve -
PRACOM1
NCT03802799 An Open-Label Extension Study Fragile X (3-18 yrs) 300 No tolerability, USA
to Assess the Long-Term Safety irritability, lethargy Australia
and Tolerability of ZYN002 New
Administered as a Transdermal Zealand
Gel to Children and Adolescents
With Fragile X Syndrome -
CONNECT-FX Open Label
Extension (OLE)

30
 NCT04219280 Evaluating Assessment and Down syndrome (6- 30 Yes ADHD USA
Medication Treatment of ADHD 17 yrs) and ADHD symptomatology
in Children With Down
Syndrome
NCT03848481 Cannabidivarin (CBDV) vs. Prader-Willi (5-30 26 Yes irritability USA
Placebo in Children and Adults yrs) and ABC-I ≥18
up to Age 30 With Prader-Willi
Syndrome (PWS)
NCT03649477 Phase 3, Randomized, Double- Prader-Willi (7-18 130 Yes hyperphagia, USA
Blind, Placebo-Controlled, 8- yrs) obsessive compulsive Canada
week Clinical Study to Assess the behaviours
Efficacy, Safety, and Tolerability,
of Intranasal Carbetocin (LV-101)
in Prader-Willi Syndrome (PWS)
With Long Term Follow-Up
(CARE-PWS)
NCT04381897 Use of N-Acetylcysteine (NAC) Cornelia de Lange 10 Yes obsessive compulsive USA
in the Treatment of Repetitive (13-35 yrs) symptoms, irritability
Behaviors (RB) and Self-
Injurious Behaviors (SIB) in
Cornelia de Lange Syndrome: A
Randomized Double-Blind
Placebo-Controlled Pilot Study
*
Current was defined as: not yet recruiting, recruiting, enrolling by invitation, active but not recruiting; The study’s primary outcome was
mental health or behavioural disorders/symptoms. ** Aberrant Behavior Checklist-Irritability subscale.97

31