Schizophrenia in mentally retarded patients

1. INDEX www.yassermetwally.com
 INTRODUCTION
INTRODUCTION
Studies that have been published in the review period have advanced understanding of the
epidemiology, presentation, assessment, suspected neuropathology, genetics and treatment of, and
service issues relating to, schizophrenia spectrum disorders in people with intellectual disabilities.
The number of published studies investigating schizophrenia spectrum disorders in people with
intellectual disabilities continues to increase slowly. The evidence base, however, needs to be
strengthened, particularly by randomized controlled trials in pharmacotherapy, psychosocial
interventions and service delivery.
The evidence base regarding schizophrenia spectrum disorders (SSDs) in people with intellectual
disabilities has been limited. This review considers the most recent studies in this area with an
emphasis on those published from January 2005 to April 2008. These studies were identified from

2. a MEDLINE literature search using the key terms of schizophrenia, psychosis, disabilities and
mental retardation. Wherever possible, this review will focus on SSDs rather than on nonspecified
psychosis, but in people with intellectual disabilities it is often more difficult to diagnose the
former, particularly as the level of intellectual disabilities increases. Thus, many studies pertain to
the less specific diagnosis of 'psychosis' rather than SSDs; so, these will also be considered here.
The term intellectual disabilities will be used, even though many of the studies cited use other
terminologies such as mental retardation and learning disabilities.
 Epidemiology
Turner[1] suggested that the point prevalence of SSDs in intellectual disabilities was at least 3%,
and this figure has been widely accepted in the literature. A lower point prevalence of psychosis of
1.3% has been recently reported in those with intellectual disabilities in a sample of more than 42
000 people living at home or in cared accommodation across Australia.[2] The interviewers for the
survey were, however, not medically trained and mental disorders were identified by self-report,
both of which would have increased the risk of nondetection of SSDs and nonaffective psychosis in
the sample.
Accurate determination of prevalence rates of SSDs in people with intellectual disabilities is
complicated by many diagnostic problems. These problems include distinguishing true
hallucinations from developmentally appropriate behaviours such as self-talk and talking to
imaginary friends. Pickard and Paschos[3] have explored this difficulty, and offered pointers
towards the differentiation of pseudohallucinations and true hallucinations, in their report of two
patients with intellectual disabilities who had been previously considered as having an SSD but
were eventually diagnosed with personality disorders.
Most of the research literature on SSDs and nonaffective psychosis in intellectual disabilities has
focused on people with mild intellectual disabilities. As intellectual disabilities become more
severe, there has been conflicting opinion on whether rates of SSDs are higher or lower. Two
recent studies[4,5] have found higher incidences of SSDs/psychosis in those with mild or moderate
intellectual disabilities compared with those with more severe intellectual disabilities. It, however,
remains unclear whether these findings reflect true prevalence rates or they merely reflect the
problems in the detection of SSDs and psychosis in people with more severe intellectual
disabilities. Cowley et al.[4] also found higher prevalence of SSDs with older age, in contrast with
an earlier study,[6] and also lower prevalence rates of SSDs in white participants compared with
nonwhites.
Tsakanikos et al.[7] found that patients with intellectual disabilities and autism referred to a
service in southeast London were not more likely to have psychosis compared with those with
intellectual disabilities but without autism. It is, however, again difficult to be sure that these
results reflect true comorbidity rates. The authors list many of the methodological problems they
encountered, including the crudeness of the screening tool Psychiatric Assessment for Adults with
Developmental Disabilities (PAS-ADD) Checklist, in detecting possible psychosis and the rating
clinicians being potentially biased by the existing diagnoses. It should also be noted that those
individuals with autism tended to have moderate or severe intellectual disability in which it is
often extremely difficult to make a clear-cut diagnosis of SSD or even nonspecified psychosis. This
may have thus resulted in the apparent lack of association between autism and psychosis.
In a study by Deb et al.,[8] it has been reported that those with schizophrenia and intellectual
disabilities were more likely to have epilepsy compared with those with typical intelligence and
with schizophrenia. Cowley et al.,[4] however, found that individuals with epilepsy and intellectual
disabilities had a lower incidence of schizophrenia than those with intellectual disabilities but
without epilepsy. In this study, the level of intellectual disabilities again may have been a

3. confounding factor, as the prevalence of epilepsy increases in more severe intellectual disabilities.
[9] Matsuura et al.[10] investigated the prevalence, psychopathology and cognitive functioning
associated with psychotic disorders among 336 adult patients with epilepsy and mild or moderate
intellectual disabilities in a Japanese multicentre study. They found a higher prevalence of
psychotic disorders among patients with intellectual disabilities than among those with normal
intelligence. Psychotic symptoms were, however, similar in presentation in patients with epilepsy
with and without intellectual disabilities. The authors noted difficulties in distinguishing psychotic
symptoms due to epilepsy from those due to schizophrenia.
 Presentation
Bouras et al.[11] found differences between presentations of SSDs in populations with and without
intellectual disabilities, using a range of rating instruments that included the Comprehensive
Psychological Rating Scale (CPRS), the Scale for the Assessment of Negative Symptoms (SANS),
the PAS-ADD Checklist, the Disability Assessment Schedule (DAS) and the Global Assessment of
Functioning (GAF). In the participants with an SSD and intellectual disabilities, they found higher
observable psychopathology, more negative symptoms and greater functional disabilities
compared with a group with SSDs but without intellectual disabilities attending a general mental
health outpatient clinic and matched for the duration of illness. These findings suggest that people
with intellectual disabilities may be more debilitated by SSDs than those without intellectual
disabilities and may thus need additional input.
The relationships between problem behaviours and SSDs in people with intellectual disabilities
remain unclear. Certainly, behavioural problems sometimes respond to antipsychotic medication.
This suggests that sometimes problem behaviours could be caused or at least exacerbated by
underlying SSDs/psychosis that is difficult, if not impossible, to diagnose clearly using standard
diagnostic criteria. Hemmings et al.[12] found no association between psychotic symptoms as
detected on the PAS-ADD Checklist and problem behaviours as rated by the DAS. Only 20 in the
sample of 214 participants were, however, recorded as having psychotic symptoms, which may
have again been due to the relative lack of sensitivity of the PAS-ADD Checklist in detecting them.
 Assessment
Sturmey et al.[13*] reported an independent replication of the psychometric properties of the
PAS-ADD Checklist. This study did find that scores for people with intellectual disabilities and
SSDs were significantly higher on the five-item psychosis scale than for those with intellectual
disabilities and other disorders or those with intellectual disabilities alone. One third of the 42
patients with SSDs, however, did not pass the threshold for detection of possible psychosis by the
PAS-ADD Checklist, representing a relatively low sensitivity rate for SSDs. The authors
speculated that these patients might have been asymptomatic at the time of assessment.
Hatton et al.[14*] investigated in a sample of people with mild intellectual disabilities the
reliability and validity of two instruments, the Positive and Negative Symptom Syndrome Scale
(PANSS) and Psychotic Symptom Rating Scales (PSYRATS), which are used for psychotic
symptoms in the population without intellectual disabilities. Scores were compared with those
achieved simultaneously on PAS-ADD scales. The PANSS positive symptoms and the PSYRATS
auditory hallucinations subscales differentiated between psychotic and nonpsychotic participants.
The PANSS negative-symptom scale and the PSYRATS delusion subscale did not differentiate
between those with intellectual disabilities and psychosis, those with intellectual disabilities and
other mental health problems and those with intellectual disabilities and no other mental health
problems.
 Neuropathology

4. Progress in neuroimaging techniques promises to aid the understanding of suspected
neuropathology in people with intellectual disabilities and SSDs. Moorhead et al.[15] compared
the distributions of grey matter found in structural magnetic resonance imaging (MRI) brain
scans of patients with comorbid intellectual disabilities with that of patients with schizophrenia,
schizophrenia alone or intellectual disabilities alone and normal controls. They found significant
grey matter reductions in the comorbid and schizophrenia groups compared with those with
intellectual disabilities alone or normal controls. It seems therefore that the brain structure of
people with intellectual disabilities and schizophrenia resembles that of people with schizophrenia
more closely than that of those with intellectual disabilities alone. The findings support the view
that comorbid schizophrenia and intellectual disabilities may often represent an early onset and
severe form of schizophrenia rather than intellectual disabilities complicated by psychosis.
 Genetics
Isolated case reports continued to be published in recent years, linking a variety of genetic
anomalies with cases of intellectual disabilities and comorbid psychosis. For example, Urruca et al.
[16] reported a case study of a patient with intellectual disabilities and psychosis associated with
an 8q21 deletion. The number of differing genetic locations reported to be associated with cases of
intellectual disabilities and SSDs/psychosis therefore continues to grow. This implies that there
will be no simple genetic relationships between intellectual disabilities and SSDs/psychosis and
thus further supports the idea of SSDs in intellectual disabilities being a collection of
heterogeneous disorders.
 Treatment
Studies report that antipsychotic medication is generally well tolerated and effective in people
with intellectual disabilities and SSDs slowly increase in number. For example, Shedlack et al.
[17*] retrospectively studied 30 patients with intellectual disabilities and SSDs and found that
there was substantial improvement in patient ratings on both the Aberrant Behavior Checklist
(ABC) and the GAF following treatment with both typical and atypical antipsychotic medication.
Antipsychotic use in people with intellectual disabilities, however, continues to be controversial.
Singh et al.[18] noted the methodological flaws in many of the existing studies of pharmacotherapy
in this patient group. The authors gave examples of inadequate study design such as the frequent
overreliance on global impression assessments for measurement of outcomes. They also pointed
out that there has been little research looking at possible cognitive side effects in this already
cognitively impaired population. Although antipsychotics probably have an overall modest
beneficial effect on cognitive functioning in people with schizophrenia,[19] it cannot be assumed
that this automatically applies also to those with both intellectual disabilities and SSDs. In their
systematic review of all studies of antipsychotic use for SSDs in people with intellectual disabilities
up to July 2004, Duggan and Brylewski[20*] found no randomized clinical trials comparing
antipsychotic medication with placebo. They concluded that until the urgent need for randomized
controlled trials is met, clinical practice would continue to depend on evidence extrapolated from
antipsychotic use in people with SSDs and with typical intelligence and from nonrandomized trials
of those with intellectual disabilities and SSDs.
Increasing attention has been paid to metabolic side effects of the newer atypical antipsychotics.
Leonard and Hoheneck[21] retrospectively studied the metabolic effects of olanzapine on 43
inpatients with intellectual disabilities. They found that olanzapine caused significant weight gain
but no other statistically significant changes in blood cholesterol, glucose and lipids. McKee et al.
[22*] also carried out a retrospective analysis of 41 institutionalized adults with intellectual
disabilities who had been prescribed atypical antipsychotics. No clinically or statistically
significant increases were observed in body mass index (BMI), blood glucose or lipids in their

5. study participants at endpoint compared with baseline. No new cases of diabetes mellitus or
hypertension were identified during the study period. This may have been because of the dietary
and exercise regimes followed by the participants, together with the 24-h nursing coverage,
systematic clinical monitoring of weight and blood pressure and regular blood testing that they
received.
Thalayasingam et al.[23] reported a case series of 24 patients with intellectual disabilities treated
with clozapine, the majority of whom had SSDs. It appears from this study that clozapine should
be safe, efficacious and well tolerated in the majority of people with intellectual disabilities and
comorbid mental illness including SSDs. The use of clozapine in the intellectual disabilities
population has been lagging behind its use in the general population and the authors considered
the likely reasons for this. Gladston and Clarke,[24] however, reported a single-case study of a
patient with intellectual disabilities, velocardiofacial syndrome and psychosis in whom clozapine
produced clear clinical improvement and also major adverse effects including seizures. Wehmeier
et al.[25] also reported case studies of a pair of female monozygotic twins concordant for
schizophrenia and mild intellectual disabilities treated with clozapine for more than 5 years. The
authors suggested that the considerable antipsychotic-induced weight gain observed in both of
these patients could have been under significant genetic influence.
Reinblatt et al.[26] examined the efficacy of electroconvulsive therapy (ECT) in 20 patients with
intellectual disabilities, including six with psychosis. Ratings were performed 1 week before ECT
treatment and one week after its termination using the ABC and the Clinical Global Impression -
Severity (CGI-S). The psychosis group had significantly lower irritability and hyperactivity scores
after treatment. The data suggest that ECT can be a useful treatment intervention for patients
with intellectual disabilities who are psychotic, particularly with symptoms of hyperactivity and
irritability.
Very little has been published regarding the use of psychosocial (including family) interventions
for people with intellectual disabilities and SSDs. Haddock et al.[27] reported a case series in
which cognitive-behavioural therapy (CBT) was adapted for five patients with psychosis and mild
intellectual disabilities. This included two cases in which family interventions were also integrated
into the individual CBT. The authors found that the CBT approach appeared to be feasible with
these patients and that it seemed to produce some benefits during a no-treatment baseline period.
Further research into the use of CBT and other psychosocial interventions in people with
intellectual disabilities and SSDs, with suitable control groups, is clearly necessary.
 Service Issues
Service consumption of, and models of service provision for, people with intellectual disabilities
and SSDs has received sparse research attention. This is surprising in view of the high health and
social care costs for people with intellectual disabilities and mental health problems. Martin et al.
[28*] reported a pilot study of assertive community treatment (ACT) for people with intellectual
disabilities (predominantly mild intellectual disabilities) who had either psychotic or affective
disorders. They found in their small sample of 20 patients (nine with psychosis) that there were no
statistically significant differences between ACT and a standard community treatment approach
in outcomes of unmet needs, carer burden, functioning and quality of life. Fidelity to the original
ACT model, however, is difficult to achieve and thus methodological problems may have
accounted for the apparent lack of additional benefit from more intensive treatment.
Cowley et al.[29] studied predictors of admission to psychiatric inpatient units in a cohort of 752
adults with intellectual disabilities in southeast London. They found that the diagnosis of SSDs
independently predicted admission for the total cohort. They also found that people who were
admitted had higher scores on the psychotic subscale total score of the PAS-ADD Checklist

6. screening instrument. It seems therefore that improving the community management of people
with intellectual disabilities and SSDs could play a crucial role in preventing their admission to an
inpatient unit.
Current service configurations mean that health and social services often do not meet the complex
needs of people with intellectual disabilities and SSDs. Catinari et al.[30] described three case
reports of adult inpatients with intellectual disabilities and SSDs that fitted with Kraepelin's
historical descriptions of 'pfropfschizophrenia'. They outlined the multiple problems that such
patients encounter in various educational and healthcare settings and argued that
'pfropfschizophrenia' is a phenotypically heterogeneous syndrome, usually treatment-refractory
and one that tends to be inadequately provided for.
 Conclusion
The relationships between intellectual disabilities and SSDs remain unclear. We are indeed
unlikely to see any clear-cut relationships between them when intellectual disabilities are
themselves on a spectrum with the general population. Historically, the majority of studies of
SSDs have excluded people with premorbid intellectual disabilities, and so the evidence base of
SSDs in people with intellectual disabilities has remained limited. This evidence base, however, is
slowly but steadily increasing. Knowledge has been improved by recent studies in the
epidemiology, presentation, genetics, suspected neuropathology, assessment and management of
SSDs in people with intellectual disabilities. Further research with those with SSDs who are
comorbid with intellectual disabilities is clearly essential. In particular, there remains a need for
randomized controlled trials of the efficacy of antipsychotic medication, psychosocial
interventions and service-delivery models in this population.
 Abbreviation Notes
ACT = Assertive Community Treatment; CBT = cognitive-behavioural therapy; ECT =
electroconvulsive therapy; PANSS = Positive and Negative Symptom Syndrome Scale; PAS-ADD
= Psychiatric Assessment for Adults with Developmental Disabilities; PSYRATS = Psychotic
Symptom Rating Scales; SSD = schizophrenia spectrum disorder
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The author: Professor Yasser Metwally
Professor of neurology, Ain Shams university school of medicine,Cairo, Egypt
http://yassermetwally.com
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