Introduction

Schizophrenia spectrum disorders (SSD) comprise of a cluster of mental disorders in which the most prominent feature is psychosis. They are more common in people with intellectual disabilities (ID) than in the general population. Operationalized criteria used to diagnose mental disorders in the general population may not be generalizable to people with ID, particularly in those with the greatest degree of disability (Clarke et al., 1994). The Diagnostic Manual – Intellectual Disability (DM-ID) (Fletcher et al., 2007) and Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC-LD)(Royal College of Psychiatrists, 2001) have been developed from the Diagnostic and Statistical Manual (DSM) and International Classification of Diseases (ICD) criteria respectively, to better serve this population, although there remains debate about their utility in improving ascertainment of SSD, especially in people with more severe ID (Melville, 2003).

Prevalence

Studies investigating the prevalence rates of SSD in people with ID report varying results. Reasons for such variation include: diversity in sampling frames; inconsistent definitions of both ID and psychosis; and differences in case ascertainment and assessment (Buckles et al., 2013). As a general estimate, schizophrenia prevalence is often quoted as 3% in people with ID, compared with an approximately 1% lifetime risk in the general population (Perälä et al., 2007).

Cooper et al. conducted a population-based cohort study of over 1000 adults with ID who were followed up for two years (Cooper et al., 2007). The point prevalence of psychotic disorders was reported as 2.6–4.4%, depending on the diagnostic criteria used, and the two-year incidence of a psychotic episode was 1.4%. Findings of this study are in agreement with an earlier work that reported a prevalence rate of schizophrenia of 4.4% in a Welsh cohort of adults with ID (Deb et al., 2001).

Morgan et al. report the results of a large study based on a population register in Western Australia. They found that between 3.7% and 5.2% of the study population had an ICD-9 diagnosis of schizophrenia, with the lifetime risk of experiencing at least one episode of non-organic psychosis to be just over 10% (Morgan et al., 2008). These results contrast with a previous Australian study, which found a lower point prevalence of 1.3% for the broader diagnosis of “psychosis” (White et al., 2005).

In a study of over 3000 inmates of British prisons, Hassiotis and colleagues not only found that people with ID were over-represented in the prison system, but also that those with ID were twice as likely as inmates of normal intelligence to have probable psychosis (Hassiotis et al., 2011). Although the time of onset of the psychosis was not recorded, it was speculated that the stressful and complex prison environment might precipitate the development of psychotic illness in those already at risk.

Risk factors

Risk factors for schizophrenia have traditionally been considered as genetic and environmental, but there is increasing evidence in support of interaction of the two in the genesis of the disorder (Van Os et al., 2008). Owing to the lack of investigation, not all risk factors have been established in the population with ID, but it might be reasonable to assume that exposures that place individuals in the general population at a higher risk of developing schizophrenia have similar effects in those with ID. However, the association of certain factors with increased rates of schizophrenia does not prove evidence of causation, and the mechanisms by which risk factors influence the development of such complex psychopathology are generally not well understood. Specific risk factors that have been investigated in people with ID include:

The nature of the link between ID and SSD

The association between SSD and intellectual functioning has prompted research in people with ID and SSD with the aim of gaining a broader understanding of the pathophysiology of schizophrenia itself (Moorhead et al., 2009). Such work has challenged the traditional view of schizophrenia as a neurodegenerative condition with onset in early adulthood (indeed, the Kraeplinian term “dementia praecox” implies a slow progressive decline arising after normal development), and a neurodevelopmental model of schizophrenia is increasingly dominant (Fatemi and Folsom, 2009; Owen et al., 2011).

Proponents of a social causative theory of schizophrenia might argue that the increased rates of social and economic disadvantage, exclusion, bullying, and adverse life events that people with ID suffer cause additional stress, which underlies the observation of increased rates of SSD (and mental illness in general) in this group (Tsakanikos et al., 2007). That is, the effects of a hostile environment are borne out by increased rates of psychopathology in vulnerable individuals. Alternatively, it may be the case that cognitive impairment in itself increases susceptibility to developing an SSD, mediated by an “overload” of an individual’s cognitive and adaptive capacity resulting from multiple episodes of only partly understood stimuli (Doody et al., 1998).

Results from imaging studies, although relatively sparse in people with ID and SSD, support a neurodevelopmental model, which maintains that SSD arise as a result of disturbed early development of the nervous system. A number of structural brain abnormalities have been described in individuals with schizophrenia, including enlargement of the ventricles, dilatation of cortical sulci, and a reduction in brain volume with proportionately greater loss in the amygdala and hippocampus, particularly on the left side. Many of the changes in gross brain morphology demonstrated in people with schizophrenia are also seen in people with ID without schizophrenia; however, imaging studies have shown the brains of people with comorbid ID and schizophrenia to show greater similarity to the brains of people of normal intelligence with schizophrenia than to a control group with ID alone (Sanderson et al., 1999). This observation leads to the suggestion that a common pathophysiological process is at work in both comorbid schizophrenia and ID and in schizophrenia alone. Therefore, the association of ID and schizophrenia may be a function of a severe and early-onset form of schizophrenia (of which the global intellectual impairment is part of the natural history of the disease), rather than the pre-existing ID itself acting as a risk factor for the development of schizophrenia (Sanderson et al., 1999; Bonnici et al., 2007). Further advocating a neurodevelopmental theory of schizophrenia is the finding that both functional decline (Fuller et al., 2002) and morphological brain changes are evident at the onset of the disease or may even predate the clinical disorder, rather than developing after the disease becomes manifest (Steen et al., 2006). Moreover, people with ID tend to develop schizophrenia at a younger age than those of normal intellectual functioning. Such findings suggest a biological underpinning to SSD, the expression of which may be influenced by later environmental exposures.

Genetic conditions and SSD

See also Chapter 18.

Several genetic conditions that cause ID are also associated with increased rates of SSD, although the mechanisms mediating the links have not been defined.

22q11.2 deletion syndrome, also known as velocardiofacial or DiGeorge syndrome, is caused by the deletion of a small region of DNA on the long arm of chromosome 22. It occurs at a population frequency of approximately 1 in 4000 live births (Botto et al. 2003). Features include facial dysmorphia, cleft palate, structural heart defects, and immune disorders in addition to mild–moderate ID. The syndrome is one of the strongest known risk factors for psychosis – 1% of people with schizophrenia are estimated to have the mutation (Horowitz et al., 2005; Bassett et al., 2010) and SSD develop in up to 41% people with the syndrome (Shprintzen, 2008; Ousley et al., 2013; Schneider et al., 2014).

Prader–Willi syndrome results from failure of expression of paternally inherited genes on the long arm of chromosome 15. Psychiatric illness is highly prevalent, particularly in the subtype caused by maternal disomy, and usually manifests as an affective psychosis (Boer et al., 2002; Soni et al., 2008; Sinnema et al., 2011).

Usher syndrome is an autosomal-recessive condition that results from defects in one of several genes. The syndrome involves ID and varying degrees of deafness, blindness, and vestibular dysfunction. The lifetime incidence of psychosis is increased, though the mechanisms underlying this association have yet to be explained (Hess‐Röver et al., 1999; Waldeck et al., 2001).

There is evidence that people with Down syndrome are less likely to be diagnosed with schizophrenia than people with ID not due to Down syndrome (Collacott et al., 1992; Mantry et al., 2008). However, whether this represents a true differential in rates of the illness is not clear.

Differential diagnosis

Several illnesses or disorders can present in a similar way to SSD and must be excluded before diagnosis, for example autism spectrum disorders (ASD) (Starling and Dossetor, 2009; Raja and Azzoni, 2010). People with ASD have impaired social interactions, commonly talk to themselves, may hold unconventional beliefs or peculiar ideas, have a high likelihood of sensory abnormalities, and often display stereotypies of speech and movement, all of which could be misinterpreted as psychosis. Poor social judgment and theory-of-mind skills may suggest paranoid delusions (Deprey and Ozonoff, 2008). However, true delusions and hallucinations are not among the symptoms of ASD (Cochran et al., 2013) (see also Chapter 11).

Difficulties in recognizing and diagnosing psychotic disorders in people with ID

Accurate diagnosis is essential to direct the correct treatment and supportive interventions.

There are no laboratory, radiological, or psychometric tests that confirm diagnosis, which is, therefore, based on clinical interview and observation. Diagnosis of SSD in people with ID can be difficult for several reasons:

There is some evidence that people with ID experience a different pattern of psychotic symptoms to people of average intelligence. In people with mild ID, the symptoms and clinical features of schizophrenia are thought to be broadly the same as the population with normal intelligence (Doody et al., 1998). The content of delusions and hallucinations will be commensurate with an individual’s developmental level, and people with ID are less likely to hold complex systematized delusional beliefs or to report conceptually complex symptoms such as passivity delusions (Meadows et al., 1991; Moss et al., 1996). Auditory hallucinations have been shown to be the most reliable and consistently reported psychotic symptom in those with mild ID (Meadows et al., 1991; Moss et al., 1996).

Bouras et al. (2004) compared people diagnosed with SSD with and without mild ID. The study found that, although the groups did not differ in terms of reported psychopathology, the group with ID showed greater levels of observable psychopathology and more negative symptoms (Bouras et al., 2004). This finding was corroborated by a meta-analysis of studies comparing the presentation of schizophrenia in people with mild ID or borderline intellectual functioning with those with average–high IQ, which demonstrated that those with lower IQ experience substantially greater negative symptoms (Welch et al., 2011). This contrasts with evidence from people with severe–profound ID in whom negative symptoms seem to be under-represented (Cherry et al., 2000), although there is, of course, inherent difficulty in diagnosing functional decline in people who may never have attained basic adaptive skills, and some authors have questioned the validity of the construct of negative symptoms when applied to people with ID (Melville, 2003; Hatton et al., 2005). In recognition of this, the DC-LD gives less significance to negative symptoms than diagnostic criteria developed for use in the general population.

In the absence of detailed self-report, observable signs of psychiatric illness that might manifest as changes in behavior and functioning are important. Maladaptive behaviors such as unexplained screaming, aggression, and self-injury, can suggest psychotic illness, particularly in those with greater degrees of impairment. Change in presentation is a particularly important indicator of the development of a psychotic illness. Collateral information is vital to establish a baseline premorbid state and family and carers should be engaged at all stages, although reliance on third-party information is not without its own complications (Costello and Bouras, 2006).

The Psychiatric Assessment Schedule for Adults with Developmental Disabilities (PAS-ADD) is a diagnostic interview suitable for direct use with people with ID and separately with informants (Moss et al., 1993). Psychotic symptoms are covered in detail, and the outcome is a specific diagnosis aligned to diagnostic criteria specified in the ICD or DSM. The Clinical Interview has been validated in the diagnosis of schizophrenia (Moss et al., 1996). The Diagnostic Assessment for the Severely Handicapped–Revised (DASH-II) is an alternative scale for use in people with severe and profound ID, and has been demonstrated to be useful in screening for schizophrenia in this group (Bamburg et al., 2001).

Management

Treatment approaches can be broadly divided into pharmacological and non-pharmacological. The evidence base for such interventions in people with ID is generally lacking and management is guided by research in the non-ID population and clinical experience.

Pharmacological treatment

See also Chapter 13.

The mainstay of pharmacological management in SSD in people with ID is antipsychotic medication. However, there is a lack of high-quality evidence for their use in people with ID (Duggan and Brylewski, 2004), and studies suggest that a significant proportion of prescribed antipsychotics are used to treat behavioral, rather than psychotic symptoms (De Kuijper et al., 2010).

Atypical antipsychotics have largely replaced older antipsychotics as first-line treatment and seem to be better tolerated (Connor and Posever, 1998; Advokat et al., 2000). Choice is determined by individual factors and the presence of comorbid conditions, and should be made jointly by practitioners and patients where possible (National Institute for Health and Care Excellence, 2014). An important side effect of atypical antipsychotics is the “metabolic syndrome” comprising of obesity, insulin resistance, impaired glucose tolerance, and dyslipidaemia (Newcomer, 2007). However, an observational study found that there were no clinical or statistically significant differences in metabolic indices between people with ID treated with antipsychotics and those who were antipsychotic naïve, although there was a trend towards increased rates of type 2 diabetes in the treated group (Frighi et al., 2011). Guidelines recommend regular monitoring of blood glucose, lipids, and weight for people taking antipsychotic medication (American Diabetes Association, 2004), although there are indications that people with ID frequently do not receive such investigations (Devapriam et al., 2009; Teeluckdharry et al., 2013).

Extra-pyramidal side effects (EPSEs) of antipsychotic medication comprise of drug-induced Parkinsonism, akathisia, acute dystonic reactions, and tardive dyskinesia. Such side effects can be persistent, impair quality of life, and may be mistaken for core symptoms or features of ID. Although the newer, atypical antipsychotics have been promoted as having less propensity to cause EPSEs than older drugs, there is evidence that those with ID who take atypical antipsychotic drugs remain at increased risk of developing abnormal movement disorders (Fodstad et al., 2010). The Matson Evaluation of Drug Side effects (MEDS) has been developed as a comprehensive informant-based measure that can be used to assess side effects of psychotropic medication in people with ID (Matson et al., 1998).

The atypical antipsychotic clozapine is effective in improving symptoms in treatment-resistant schizophrenia (Kane, 1992). It is licensed where two adequate trials of alternative antipsychotics have failed. Studies suggest that clozapine is safe and efficacious in people with ID (Antonacci and De Groot, 2000; Thalayasingam et al., 2004). Clozapine has also been used to treat aggression in people with ID with some success in small trials (Cohen and Underwood 1994), but a more recent review concluded that “research on the use of clozapine to manage behavior among individuals with ID is inconclusive at best” (Singh et al., 2010). In addition, the risk of serious side effects, including potentially fatal agranulocytosis, and necessity of regular blood tests may deter clinicians from using the drug.

Non-pharmacological treatment

See also Chapter 15.

Psychosocial interventions are often used in combination with medication and require input from the wider multidisciplinary team. A broad range of psychosocial interventions has been used, including cognitive-behavioral therapy (CBT), psychoeducation programs, and family-based interventions (Chien et al., 2013). The focus may be on managing or reducing symptoms, psychoeducation and improving insight, or maximizing functional ability. Delivery of therapies needs to be adapted to reflect a person’s developmental level, which may involve incorporating flexibility in the location and structure of sessions, and supporting the individual with prompts or accessible written information.

Case reports detailing successful group and individual interventions for people with ID and SSD have been published (Crowley et al. 2008; Hurley 2012; Allott et al. 2013), but interventions have not been systematically evaluated and robust evidence of their effectiveness and acceptability is lacking.

Psychosis co-occurring with ID confers additional carer burden (Irazábal et al., 2012) and efforts should be made to involve and support family carers (National Institute for Health and Care Excellence, 2014). Research in the mainstream population has consistently demonstrated the effectiveness of family therapy in improving several aspects of the condition, including frequency of relapse and number of admissions to hospital (Pharoah et al., 2010). Although further research is required, adapted family therapy shows signs of being a promising treatment in people with ID (Marshall and Ferris, 2012).

Service provision

The majority of people with ID and psychosis will be managed in the community and their usual home. People with ID and SSD are likely to be heavy consumers of psychiatric resources (Spiller et al., 2007). Amongst people with ID suffering mental illness, those with schizophrenia have been shown to use psychiatric services more than those with any other diagnosis (Morgan et al., 2008). Despite this, there has been little research to inform the most effective models of community care (Balogh et al., 2008; Hemmings, 2008). A consultation exercise involving a large multidisciplinary group identified the “need for a focused approach on the service user and their illness” and “working within the wider context of the service user” as essential components of services managing people with ID and psychosis (Hemmings et al., 2009).

Assertive community treatment (ACT) teams are a feature of many mainstream psychiatric services and work with people with severe and chronic mental illness who engage poorly with services (Stein and Test, 1980). Evaluation of such services for people with ID have failed to show evidence of improvement in any outcome measure (Oliver et al., 2002; Martin et al., 2005).

At times of symptom exacerbation or where the risk associated with the illness is too great, facilities for hospital admission must be available. Being diagnosed with a schizophrenia spectrum condition increases the likelihood of having a psychiatric admission over people with other psychiatric diagnoses (Cowley et al., 2005). Moreover, a study conducted in Taiwan found that hospital admissions for people with ID and co-occurring schizophrenia cost more than admissions for people with ID and other mental illnesses (Lai et al., 2011).

Whether psychiatric services for people with ID who develop serious mental illness, including SSD, are provided within specialist ID teams or by generic mental health services is the focus of a, as yet unanswered, debate (Hemmings et al., 2014).

Outcome/prognosis

The “recovery model” of rehabilitation from serious mental illness has gained currency in the general population. Advocates from within both professional and service user and carer populations uphold that principles of hope, healing, and empowerment should drive the development of positive, person-centered services that work collaboratively with, and are acceptable to, users of those services (Warner, 2009). Under this model, recovery is not merely remission from symptoms but implies broader gains in social and functional outcome. Respect for the individual’s experience and their priorities are at the heart of the model. Although the concept of “recovery” from SSD in this sense has sparsely been covered in people with ID, certain aspects of the model, such as supported employment, social skills training, and promotion of community inclusion, will be familiar to those working in ID services.

Despite the optimism inherent in the recovery model, SSD tend to run a chronic course and can impair relationships, functioning, and quality of life (Morgan et al., 2008; Jääskeläinen et al., 2013). A study by Cooper and colleagues reported a full remission rate of just under 15% over a two-year period (Cooper et al., 2009).

When comparing people with SSD with and without co-occurring ID, studies have shown people with borderline intellectual functioning or diagnosed ID have a more severe illness, greater functional disability, and lower quality of life (Bouras et al., 2004; Chaplin et al., 2006).