Is autism spectrum disorder common in schizophrenia?

Abstract

A century ago, Kraepelin and Bleuler observed that schizophrenia is often antedated by “premorbid” abnormalities. In this study we explore how the childhood neurodevelopmental problems found in patients with schizophrenia relate to the current concept of autism spectrum disorder (ASD). Forty-six young adult individuals with clinical diagnoses of schizophrenic psychotic disorders were assessed. The Structured Clinical Interview for DSM Disorders (SCID-I) was used in face-to-face psychiatric examination of each individual. In 32 of the 46 cases (70%), collateral information was provided by one or both parents. The Diagnostic Interview for Social and Communication Disorders — eleventh version (DISCO-11) was used when interviewing these relatives. This instrument covers, in considerable depth, childhood development, adaptive functioning, and symptoms of ASD — current and lifetime. There is a strict algorithm for ASD diagnosis. About half of the cases with schizophrenic psychosis had ASD according to the results of the parental interview. The rate of ASD was strikingly high (60%) in the group with a SCID-I diagnosis of schizophrenia paranoid type. The findings underscore the need to revisit the DSM's “either or” stance between ASD and schizophrenia.

Introduction

Although the typical symptoms of schizophrenia usually appear in young adulthood, precursors of the disorder may be present during childhood. Children who, in their late teens or adulthood, develop schizophrenia have been described as slightly different from their age peers with regard to motor performance, cognitive development, activity control and social interaction. Even though there have been many of studies of these phenomena, the nature of the neurodevelopmental deviations is still poorly understood.

In the prospective study of the British 1946 birth cohort, differences between children who developed schizophrenia as adults and the general population were found in a range of developmental domains. Speech problems, low educational test scores, solitary play preference, and self-reported anxiety in social situations during childhood were factors associated with schizophrenia in adulthood (Jones et al., 1994). Another extensive cohort-study, the National Child Development Study, found that individuals who later developed schizophrenia differed from schoolmates in several social and emotional domains (Done et al., 1994, Leask et al., 2002). Deviant behaviours at age 4 years and both social and language impairment by age 7 years were found in another prospective cohort study by (Bearden et al., 2000).

Home-videos of patients with schizophrenia as children have been analysed in comparison with siblings in a unique study by Elaine Walker (Walker et al., 1993, Walker et al., 1994). According to this, children who later developed schizophrenia showed more negative emotions and frequently had unusual motoric features compared with their healthy siblings. In 1972 a sample of young Danish children (age 11–13) were videotaped in a standardized condition as part of the Copenhagen High-Risk Study (Schiffman et al., 2004). Adult psychiatric status was later ascertained. The analysis of the videotapes showed that the individuals who developed schizophrenia, as a group, showed deficits in sociability.

Given that genetics are important risk factors for schizophrenia, several high-risk studies have longitudinally followed children who have one or two parents with schizophrenia. Problems in motor and neurological development, deficits in attention and verbal short-term memory, and poor social competence are factors that appear to predict schizophrenia in these studies (Erlenmeyer-Kimling and Cornblatt, 1987, Mednick et al., 1987, Weintraub, 1987, Erlenmeyer-Kimling et al., 2000, Niemi et al., 2003).

Greater awareness about children's circumstances and of the consequences of neurodevelopmental disorders in childhood has led to an increased concern regarding early identification and support of children with such difficulties. Autism Spectrum Disorder (ASD) is considered as a neurodevelopmental disorder with a spectrum of signs and symptoms, the essential features being a triad of impairments of social interaction, communication and imagination. ASD is recognised in children with normal as well as subnormal intelligence. ASD was, until recently, assumed to be a rare condition, but according to recent epidemiologic studies using DSM-IV or ICD-10 criteria, the prevalence of ASD is 0.5–1% of the child population (Baird et al., 2006, Fombonne et al., 2009). Symptoms should be present from infancy or early childhood, but they may not become fully manifest until social demands exceed limited capacities (www.dsm5.org). Autism is now diagnosed for the first time in adults and even in elderly people (van Niekerk et al., 2010). This confirms that although autism is present from childhood, it is not always recognized and addressed during the early years.

Genetic studies have shown numerous direct and indirect links between ASD and schizophrenia (McCarthy et al., 2009, Craddock and Owen, 2010). Specific copy number variants associated with schizophrenia are also linked to a range of neurodevelopmental disorders including ASD, intellectual disability and ADHD (Owen et al., 2011). Neurexin-1, a vulnerability gene for both schizophrenia and ASD, has been proposed to influence brain structure and cognitive function susceptible in both disorders (Voineskos et al., 2011). Family history data support a link between ASD and schizophrenia (Ghaziuddin, 2005).

Neuroimaging studies have shown appreciable brain structural concordances between autism and schizophrenia (Cheung et al., 2010). In a magnetic resonance imaging study by Toal et al. (2009) adults with ASD with or without a history of psychosis and healthy controls were compared. The group with ASD differed from controls in brain regions that are also implicated in schizophrenia. The authors put forward ASD as an alternative ‘entry-point’ into schizophrenia based on developmental brain abnormalities, suggesting that people with ASD may only require relatively subtle additional abnormalities to develop the positive symptoms of psychosis such as delusions and hallucinations.

Childhood onset schizophrenia, i.e. schizophrenia with onset prior to the age of 13 years, is a rare, very severe condition with poor long-term prognosis. It is antedated by (and “comorbid” with) ASD in 30–50% of the cases (Sporn et al., 2004, Rapoport et al., 2009).

The aim of the present study was to examine the rate of ASD in patients with a clinical diagnosis of schizophrenia, to analyse whether or not ASD is more common in any particular subtype of schizophrenia or if any specific subtype of ASD is more strongly related to schizophrenia, and to evaluate the effect, if any, of gender on any possible association between the two categories.