Psychiatric co-morbidities in autistic spectrum disorders.

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Eleri Clissold
London Division Essay Prize 2012
The Royal College of Psychiatrists London Division
Essay Prize 2012
Suffering in silence
Psychiatric co-morbidities in autistic
spectrum disorders
Name: Eleri Clissold
Medical school: King’s College London
Email: eleri.clissold@kcl.ac.uk
Word count: Total 4,449
Abstract: This essay briefly summarizes the current literature regarding
depression in those with autistic spectrum disorders (ASD) and in doing so
illustrates the urgent need for further research in this area. The prevalence of
depression in ASD remains unclear although is likely to be significantly greater
than in the general population. Presentation is complex and heterogeneous.
Challenges in the diagnosis of depression in ASD are broadly two-fold; 1)
features of ASD which overlap with depression and 2) features limiting the
expression of depression. This is complicated by the absence of a specific
diagnostic framework for this condition. Many areas of depression in ASD remain
poorly understood including treatment and aetiology; however it is thought that
depression in this group responds to conventional anti-depressive therapy. This
essay briefly explores the role which stigma and a lack of support may play in the
development of depression in ASD. Conclusion: There is a dire need for a
sizeable and reliable evidence base in this area, this would significantly reduce
preventable suffering in this group. The possibility that social factors may be
driving such suffering requires urgent exploration.
Eleri Clissold
London Division Essay Prize 2012
Introduction
Autism has come a long way from Kanner’s “infantile schizophrenia”1 and
misguided notions of “refrigerator mothers” 2 to a well-recognized pervasive
developmental disorder. Today the National Autistic Society has over 20,000
members and educational interventions, such as the Picture Exchange
Communications System, have transformed the prospects of many3-5 (p.37). The
prevalence of autism has grown steadily over the last four decades and shows no
sign of abating with 1% of school children currently estimated to suffer some
form of autism6. With this in mind research into this area has never been timelier.
The numerous and frequent physical co-morbidities associated with autistic
spectrum disorders (ASD) are well documented in the literature. However it is
only within the last decade that psychiatric co-morbidities have begun to receive
due recognition in both research and clinical practice, with meta-analyses of
what sparse data exists and clear, concise calls for further research7,8.
This essay will briefly review literature concerning depression in ASD
which is widely considered the most common and best documented of autism’s
psychiatric co morbidities8. In doing so the aim is to highlight the alarming lack
of literature on the subject and speculate as to consequences and causes of this
trend. Autistic spectrum disorders (ASD) in this context will refer to autism,
PDD-NOS (Pervasive Developmental Disorder Not Otherwise Specified, when the
diagnostic criteria for autism are partially fulfilled), high-functioning autism
(HFA) and Asperger’s syndrome (AS). This essay will assume the ICD-10
definition, that autism involves a developmental impairment recognised before
the age of three years with three key areas of psychopathology; communication,
social interaction, and stereotyped, repetitive behaviour. Additional common
problems include temper tantrums, aggression towards self or others, phobias,
disturbed sleep, and abnormal eating patterns. Where learning disability (LD) is
referred to this is assumed to mean an IQ of below 709. Given the limited
material concerning depression in ASD this discussion will lay aside extensive
nosological debate on the role of AS within the autistic spectrum (see Matson &
Wilkins10) and consider the entire autistic spectrum including AS, across all age
groups. It is important to note the vast variation within the autistic spectrum,
from non-verbal and highly dependent to those with AS or HFA with little to no
LD and who may be in employment or may be parents11. For the purposes of this
essay this variation will only be taken into account where existing material on
the subject allows. It is likely that in practice the presentation and needs of those
with ASD and depression will vary as greatly as the autistic spectrum itself.
Throughout this essay the term depression will refer to isolated or
recurrent episodes of classical mild, moderate or severe depression in the
absence of mania. Clinically this classically presents with low mood (with diurnal
variation), reduced energy and a decrease in activity. Additional symptoms
include reduced concentration, libido, interest, and capacity for enjoyment,
marked tiredness after minimum exertion, disturbed sleep and appetite, ideas of
guilt or worthlessness and low self-esteem and self-confidence9.
Prevalence
The prevalence of depression and autism in any age group is yet to be
conclusively established. Some commentators have estimated the figure as high
as 65%12 although 5-34% is a more accepted range8(p.105). This sizeable variation
Eleri Clissold
London Division Essay Prize 2012
is likely due to the dramatic differences in methodology; study setting, sample
size, diagnostic criteria, sampling techniques and study period. A recent
literature review noted that the largest study had just 85 participants with most
studies either published as case reports or clinic studies with around 20
participants8(p.108). In the absence of large scale, population based studies the
precise prevalence of co-morbid depression in ASD will remain unclear. With
such variation in methodology it could be argued that there may not be a
significant relationship between depression and autism, however numerous case
reports, small scale studies and an abundance of anecdotal evidence over the
past 60 years strongly suggests a high frequency of coexistence7. Furthermore
Kim and colleagues13 found a prevalence rate of depression of 16.9% in children
aged 10-12 years with HFA and AS when followed up over six years. This result
was significant when compared to a control group in the community. In the same
year point prevalence of depression in the UK was in the range of 3-7%14 and
was thought to be 1.8% in pre-pubertal school aged children in 199515. The
prevalence of depression in the general population appears to be substantially
lower than all estimates of depression in autistic populations8. It therefore seems
reasonable to assume a trend worthy of further investigation exists.
Presentation
Depression in ASD embodies the same features as depression in the general
population although the way those features are expressed in ASD is extremely
variable16. Some diagnostic challenges are identical to those faced in diagnosing
co-morbid depression in LD, although many are related to features unique to
autism17. Commonly reported symptoms are increased irritability or crying and
sad facial expressions. However facial expressions in ASD are characteristically
neutral or difficult to interpret and both verbal and non-verbal communication is
limited. Communication difficulties are especially pronounced around
mentalizing and expressing complex emotions such as shame and
embarrassment. In combination these factors impair the expression of
depressive symptoms18-20. Consequently cases are almost exclusively reported
by a third party - parent, carer or health care professional (see Ghaziuddin &
Tsai21 for an exception) - and often present when the disease has progressed
significantly22. Other common symptoms are changes in sleep and appetite, most
often although not exclusively, insomnia8. However sleep disturbance is a
common feature of ASD in the absence of psychiatric co-morbidities. A recent
study found 37.5% of children with autism suffered from chronic sleep problems
compared to just 8.6% of controls and that those in the control group were more
likely to remit over time23. Similarly loss of interest, social withdrawal and
psychomotor retardation have been cited as symptoms of depression in ASD,
however the social dysfunction and abnormal patterns of speech commonly
observed in autism may well enhance or obscure such symptoms. Other less
common depressive symptoms in HFA and AS include suicidal ideation,
attempted or completed suicide and alcoholism20,22 Some symptoms notably
associated with the autistic spectrum have been shown to increase or begin with
the onset of depression, namely aggression, injury to self, total withdrawal and
oppositional behaviour (e.g. refusing to leave home). Although it is important to
note that other factors – such as stress, change in routine or physical illness –
and not solely depression may result in an increase in such behaviours8.
Eleri Clissold
London Division Essay Prize 2012
Paradoxically there has been speculation as to whether depression may decrease
other maladaptive behaviours. Obsessions and repetitive behaviours are key
features of autism, playing a crucial role in diagnosing the condition as one of
three key areas of psychopathology in the ICD-10 criteria9. Repetitive behaviours
can vary from simple echolalia and hand flapping to more complex ritualistic
behaviours. Such behaviours have been shown to predict the severity of autism
and can cause substantial parental anxiety24,25. If these maladaptive behaviours
decrease in frequency, this will often be viewed as an improvement in the
individual rather than a feature of a depressive illness. Although there is little
evidence behind this theory cases have been reported of depressed individuals
losing interest in repetitive behaviours and obsessional themes26.
Complex behaviours unique to autism and features related to LD muddy
the waters when it comes to identifying depression. Clearly the presentation of
depression in the autistic spectrum is multi-faceted and not yet fully understood.
Mis-diagnosis or a failure to diagnose is therefore understandably a significant
risk.
Diagnosis
In spite of such significant risks no specific diagnostic criteria of any kind, selfreported or third-party, exists. In the absence of such a framework it is likely that
an approach in clinic similar to that advocated by Lainhart & Folstein27 may be
taken. Firstly deterioration in activity, behaviour, language or cognition is
considered. This is then placed in the context of that individual’s baseline
interests and activity, and a pattern established. Finally a mental state is taken,
directly or by collateral history, with particular interest paid to symptoms of
depression particular to autism. In light of this it is understandable that some
commentators consider it essential for all psychiatrists to have an in-depth
understanding of ASD28. Studies have previously attempted to use a number of
different pre-existing scales with varying degrees of success. The Beck
Depression Inventory29 and the Hamilton rating scale for depression30 arguably
constitute the gold standard in assessing and monitoring depression. However
they’re seldom used in the context of autism as, although core in classical
depression, feelings of guilt, anxiety, suicidality and reduced concentration levels
are infrequently reported symptoms of depression in ASD8. Unsurprisingly
where these scales have been administered several items were unrecordable.
Even when adapted, many questions remained challenging for the individual in
question or for their carers to answer on their behalf, such as subjectively rating
mood21. Equally by these frameworks assessment of interest in activities, social
withdrawal, psychomotor retardation, sleep and appetite may be misleading
whilst autism-specific maladaptive behaviours remain unassessed8. Conversely,
reflecting the significant variation in abilities within the autistic spectrum, selfreporting scales have been used with some success in AS. One account reports
how the structured nature of the Children’s Depression Inventory (a derivative
of the Hamilton30 rating scale for depression) and the ability to explain his mood
using numbers appealed to the individual’s style of thinking31. Other studies have
used semi-structured interview tools based on DSM-III-R criteria; the Diagnostic
Interview for Children & Adolescents32, the revised Ontario Child Health Study33
and the Kiddie Schedule for Affective Disorders & Schizophrenia34. Although
specific to children they screen for a number of psychiatric conditions and again
Eleri Clissold
London Division Essay Prize 2012
fail to account for features of depression unique to autism8. Similarly the
Disability Assessment Schedule35 and the Reiss scale36 consider a wide range of
behavioural abnormalities (including non-verbal communication and social
interaction), are specific to LD, carer-rated and retrospective although again
screen for a wide array of psychiatric conditions.
Seemingly no scale or rating system ticks all the required boxes, however
a more recent diagnostic criterion for LD may hold promise. This framework
ignores complex emotions and suicidal ideation, focusing instead on other DSMIV criteria such as loss of confidence, tearfulness, increased reassurance seeking
and challenging behaviours37. Stewart et al8 concluded that modifying the DC-LC
was essential, and suggested suitable adjustments to the scale, namely; recurrent
thoughts of death (not simply fears of dying), incontinence and an increase in
aggression (towards self or others).
Treatment
Given the uncertainty in prevalence and highly variable presentation it follows
that randomised control trials of anti-depressant therapy in this patient group
are lacking. However, the existing evidence is encouraging. Both depressive
symptoms and behavioural problems have been observed to improve with
pharmacological treatment38,39. Isolated cases have also been noted of successful
treatment with electro-convulsive therapy and cognitive behavioural therapy40.
There have also been reports of depression only being recognised once antidepressant treatment has been administered8. This could mean that depressive
symptoms in ASD are a variant presentation of this common affective disorder
and therefore less likely to form part of the autistic phenotype.
Predisposing, precipitating & perpetuating factors
The role of affective disorders within the autistic phenotype has been the subject
of much debate and without a clear understanding of the genetic basis of autism
it’s likely that this debate will remain unresolved41. Until genetic predisposition
is better understood it seems prudent if not essential to question the role of
other precipitating and perpetuating factors. A well-established feature of autism
is the tendency for minor environmental change to cause extreme distress. This
distress and subsequent resistance to the unexpected is thought to be due to a
difficulty in understanding environmental change leading to fear and
uncertainty42. It is unsurprising therefore that high levels of anxiety have been
noted in this group43. Depression and anxiety have a complex relationship and
studies in non-autistic populations have shown anxiety to underlie many cases of
depression44. Reproducing this work in those with ASD would certainly be of
merit.
Equally there is limited research into the impact of life events, social
circumstances and quality of life on depression in this group8. It should be noted
that in all likelihood precipitants of depression in the general population are
likely apply to those with ASD e.g. bereavement or loss, loneliness, feeling a
failure and sexual frustration. Many of these precipitants may be more
commonly experienced by those with ASD due to pressures on the family and
complex social circumstances resulting from autism22. Affective disorders are
thought to occur at a higher rate in parents of children with autism than in
parents of non-autistic children. Although this has caused much academic
Eleri Clissold
London Division Essay Prize 2012
interest into a potential genetic link between parental affective disorder and
autism, this phenomenon is far from understood40.
There is also an abundance of qualitative evidence suggesting that
perceived stigma and lack, or perceived lack, of social support are major
precipitants (e.g. Mickelson45, 2001; Gray & Holden23, Gray46). Testament to this
is the fact that over 50% of children are not in the kind of schooling environment
their parents believe would support them best and one fifth of have been
excluded from school at some point47. Depression is thought to be more common
in those with HFA and AS as opposed to other forms of autism because of a
deeper insight into the condition and a heightened sense of this social isolation
and stigma7,39. Depression in ASD is thought to peak during late adolescence and
early adult years and a direct link between high levels of peer victimization and
suicidal ideation has been shown in this group16,20. 40% of young people with
ASD have experienced some form of bullying, some have even been accused of
harassment in their attempts to form relationships. Autism advocacy groups cite
lack of support as a major obstacle and cause of mental illness for those with
autism in the UK, with only around a third of autistic adults in England reporting
that they feel adequately supported. Despite 61% of those out of employment
saying they would like to work just 15% of adults with autism are currently
employed5,46,48.
With over whelming social isolation, a lack of support, unemployment and
subsequent low self-worth it’s clear that social factors have a major role in
depression in ASD.
Conclusion
Throughout this essay a lack of high quality data - in prevalence, presentation,
treatment and aetiology - has been a theme. This has posed a significant problem
in attempting to draw meaningful conclusions, although clearly illustrates the
principal argument of this essay: that there is evidence to suggest that extensive
research in this area is urgently needed. Depression has consistently been
estimated at a significantly higher rate in autistic groups than in the general
population. By its very nature ASD places pressure on carers and health care
professionals to recognize and report psychiatric co-morbidities however
diagnosis is complex and fraught with pitfalls, especially for clinicians without an
in-depth knowledge of the autistic spectrum49. In addition most studies use child
or adolescent samples when it’s widely agreed that adolescents and young adults
are more prone to depression than children16. All this considered and in the
absence of a suitable diagnostic framework it seems entirely likely that the
prevalence of this condition may be higher than many studies estimate. As a
result individuals with autism may be silently suffering the debilitating effects of
depression in the face the effective treatment.
Reports of diagnoses being made on the basis of therapeutic trials of antidepressants are further support of this. Thorough scientific exploration of this
area would also be of nosological merit. Conclusively establishing the role of
affective disorders in the autistic phenotype seems highly unlikely until the
genetic basis of autism is better understood. That said it stands to reason that a
solid understanding of how social factors influence the development of affective
disorders in those with ASD could help strongly inform hypotheses in this area.
Eleri Clissold
London Division Essay Prize 2012
Similarly Klin and colleagues13 attempted to use depression as a means of
distinguishing AS from HFA.
Despite significant advances in the disability right’s movement and in
understanding autism, those effected by autism face alarming levels of stigma
and social isolation. It seems some of the most pressing work lies around
establishing the precise relationship between stigma, social support and mental
health in this population. If depression is being driven even in part by a social
phenomenon then social interventions - campaigns, policies and education become as or even more important than pharmacological treatments, as an
element of this suffering is then preventable rather than merely treatable.
Just fifteen case reports of co-existent ASD and depression have been
documented in the literature over six decades. In spite of a clearly documented
high parental rate of affective disorders there has been little speculation as to the
link between parental depression and depression in children with ASD. Kanner
himself noted a tendency to “momentary fits of depression” within his original
cohort1 and yet psychiatric co-morbidities have been neglected in the literature,
especially when compared to physical co-morbidities of ASD. Could we be
prejudiced as a medical profession? Or perhaps hold a misconception that
depression doesn’t affect those with severe LD? This is clearly something that
warrants extensive further consideration. This essay inevitably raises more
questions than answers although has clearly demonstrated a pressing need for
research surrounding depression in ASD, particularly with regards to prevalence
and social precipitants.
Eleri Clissold
London Division Essay Prize 2012
Acknowledgements
Many thanks to the staff, patients and families at the King’s College London Child
& Adolescent Psychiatry unit for igniting my interest in neuropsychiatry. In
particular thank you to my supervisor Dr M.T. Lax-Pericall for her guidance in
writing this essay.
Eleri Clissold
London Division Essay Prize 2012
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London Division Essay Prize 2012
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London Division Essay Prize 2012
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