Schizophrenia in mentally retarded patients

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Schizophrenia in mentally retarded patients

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Schizophrenia in mentally retarded patients

  1. 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. 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. 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. 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. 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. 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 References 1. Turner TH. Schizophrenia and mental handicap: an historical review, with implications for further research. Psychol Med 1989; 19:301-314. 2. White P, Chant D, Edwards N, et al. Prevalence of intellectual disability and comorbid mental illness in an Australian community sample. Aust N Z J Psychiatry 2005; 39:395-400. 3. Pickard M, Paschos D. Pseudohallucinations in people with intellectual disabilities: two case reports. Ment Health Asp Dev Disabil 2005; 8: 91-93. 4. Cowley A, Holt G, Bouras N, et al. Descriptive psychopathology in people with mental retardation. J Nerv Ment Dis 2004; 192:232-237. 5. Holden B, Gitleson JP. The association between severity of intellectual disability and psychiatric symptomatology. J Intellect Disabil Res 2004; 48:556-562.
  7. 7. 6. Cooper SA. Epidemiology of psychiatric disorders in elderly compared with younger adults with learning disabilities. Br J Psychiatry 1997; 170: 375-380. 7. Tsakanikos E, Costello H, Holt G, et al. Psychopathology in adults with autism and intellectual disability. J Autism Dev Disorders (in press). 8. Deb S, Thomas M, Bright C. Mental disorder in adults with intellectual disability. Prevalence of functional psychiatric illness among a communitybased population aged between 16 and 64 years. J Intellect Disabil Res 2001; 45:495-505. 9. Bowley C, Kerr M. Epilepsy and intellectual disability. J Intellect Disabil Res 2000; 44:529- 543. 10. Matsuura M, Adachi N, Muramatsu R, et al. Intellectual disability and psychotic disorders of adult epilepsy. Epilepsia 2005; 46 (Suppl 1):11-14. 11. Bouras N, Martin G, Leese M, et al. Schizophrenia-spectrum psychoses in people with and without intellectual disability. J Intellect Disabil Res 2004; 48:548-555. 12. Hemmings CP, Gravestock S, Pickard M, Bouras N. Psychiatric symptoms and problem behaviours in people with intellectual disabilities. J Intellect Disabil Res 2006; 50:269-276. 13. Sturmey P, Newton JT, Cowley A, et al. The PAS-ADD Checklist: independent replication of its psychometric properties in a community sample. Br J Psychiatry 2005; 186:319-323. 14. Hatton C, Haddock G, Taylor JL, et al. The reliability and validity of general psychotic rating scales with people with mild and moderate intellectual disabilities: an empirical investigation. J Intellect Disabil Res 2005; 49: 490-500. 15. Moorhead TWJ, Job DE, Whalley HC, et al. Voxel-based morphometry of co-morbid schizophrenia and learning disability: analyses in normalized and native spaces using parametric and nonparametric statistical methods. Neuroimage 2004; 22:188-202. 16. Urruca N, Arenas-Sordo M, Ortiz-Dominguez A, et al. An 8q21 deletion in a patient with comorbid psychosis and mental retardation. CNS Spectr 2005; 10:864-866. 17. Shedlack KJ, Hennen J, Magee C, Cheron DM. Assessing the utility of atypical antipsychotic medication in adults with mild mental retardation and comorbid psychiatric disorders. J Clin Psychiatry 2005; 66:52-62. 18. Singh AN, Matson JL, Cooper CL, et al. The use of risperidone among individuals with mental retardation: clinically supported or not? Res Dev Disabil 2005; 26:203-218. 19. MacCabe JH, Murray RM. Intellectual functioning in schizophrenia: a marker of neurodevelopmental damage? J Intellect Disabil Res 2004; 48:519-523. 20. Duggan L, Brylewski J. Antipsychotic medication versus placebo for people with both schizophrenia and learning disability. Cochrane Database Syst Rev 2004; (4):CD000030. 21. Leonard H, Hoheneck D. Metabolic side effects of the atypical antipsychotic in an inpatient population of adults with developmental disabilities. Ment Health Aspects Dev Disabil 2006; 9:18-22.
  8. 8. 22. McKee JR, Bodfish JW, Mahorney SL, et al. Metabolic effects associated with atypical antipsychotic treatment in the developmentally disabled. J Clin Psychiatry 2005; 66:1161- 1168. 23. Thalayasingam S, Alexander RT, Singh I. The use of clozapine in adults with intellectual disability. J Intellect Disabil Res 2004; 48:572-579. 24. Gladston S, Clarke DJ. Clozapine treatment of psychosis associated with velo-cardio-facial syndrome: benefits and risks. J Intellect Disabil Res 2005; 49:567-570. 25. Wehmeier PM, Gebhardt S, Schmidtke J, et al. Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation. Psychiatry Res 2005; 133:273-276. 26. Reinblatt SP, Rifkin A, Freeman J. The efficacy of ECT in adults with mental retardation experiencing psychiatric disorders. J ECT 2004; 20:208-212. 27. Haddock G, Lobban F, Hatton C, Carson R. Cognitive-behaviour therapy for people with psychosis and mild intellectual disabilities: a case series. Clin Psychol Psychother 2004; 11:282-298. 28. Martin G, Costello H, Leese M, et al. An exploratory study of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues. J Intellect Disabil Res 2005; 49:516-524. 29. Cowley A, Newton J, Sturmey P, et al. Psychiatric inpatient admissions of adults with intellectual disabilities: predictive factors. Am J Ment Retard 2005; 110:216-225. 30. Catinari S, Vass A, Ermilov M, Heresco-Levy U. Pfropfschizophrenia in the age of deinstutionalisation: whose problem? Compr Psychiatry 2005; 46:200- 205. The author: Professor Yasser Metwally Professor of neurology, Ain Shams university school of medicine,Cairo, Egypt http://yassermetwally.com To access all issues in quot;talking psychiatryquot; section of quot;http://yassermetwally.netquot; follow the link : http://wordpress.com/tag/talking-psychiatry/ or click on if it appears as a link in your PDF reader

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