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Autism and Schizophrenia

Autism and Schizophrenia

Autism and SchizophreniaEmerging study results suggest that there are both clinical and biological links between autism and schizophrenia. The question regarding whether there is phenotypic overlap or comorbidity between autism and schizophrenia dates back to 1943, when Kanner1 first used the term “autism” to describe egocentricity. The distinction between the two disorders remained unclear for nearly 30 years, until DSM-II included children with autism under the diagnostic umbrella of schizophrenia, childhood type. In 1971, Kolvin2 conducted seminal research that highlighted the distinction between autism and schizophrenia, which influenced the decision to include the disorders as 2 separate categories in DSM-III.

The patient’s age at the onset of symptoms and the clinical presentation distinguish autism from early-onset schizophrenia. Also, the disorders are treated differently.2,3 Schizophrenia is thought to develop at a chance rate in individuals with autism. It is noteworthy, however, that children who have childhood-onset schizophrenia (COS) show fairly high premorbid rates of early developmental abnormalities.2,4-7

This article highlights the biological and clinical links between autism and schizophrenia.

Childhood-onset schizophrenia

COS—the onset of psychosis before age 13 years—is considered a rare and severe form of schizophrenia. Systematic studies of COS show high rates of the disorder being either preceded by or comorbid with autistic spectrum disorders (ASD).7

The first to describe the severity and frequency of prepsychotic developmental disorders in COS was Kolvin,2 who noted deficits in communication, motor development, and social relatedness. These deficits were found in 28% to 55% of children with ASD, and these observations have been replicated in multiple studies.6-8

Retrospective studies of children with schizophrenia reveal delays in language acquisition and visual-motor coordination during early childhood before the onset of psychotic symptoms.9 Alaghband-Rad and colleagues10 reviewed the premorbid histories of children with COS and noted language delays and transient motor stereotypies (patterned repetitive movements, postures, and utterances). Their findings suggest early developmental abnormalities of the temporal and frontal lobes as evidenced by prepsychotic language difficulties; the early transient motor stereotypies indicate developmental abnormalities of the basal ganglia.

Shared clinical features

Although the disorders are distinct, they have shared clinical features. Social withdrawal, communication impairment, and poor eye contact seen in ASD are similar to the negative symptoms seen in youths with schizophrenia.11 When higher-functioning individuals with autism are stressed, they become highly anxious and at times may appear thought-disordered and paranoid, particularly when they are asked to shift set (such as being asked to change a topic of conversation or to stop an activity that they are engaged in and begin a new activity).12 A subset of children (28%) in the ongoing NIMH study of COS have been reported to have comorbid COS and ASD.7

A number of researchers use different terms to describe this complex mix of psychiatric comorbidity and developmental psychopathology. At the Yale Child Study Center, a subgroup of children with ASD was labeled as having multiplex developmental disorder.13,14 Researchers in the Netherlands used the term “multiple complex developmental disorders” (MCDD) to describe children who met criteria for ASD and also exhibited affect dysregulation and disordered thinking.15-18 Of significant interest are follow-up studies, which showed that psychosis developed by adulthood in 64% of children with MCDD.16

Similarly, a study by Sprong and colleagues19 that compared youths with MCDD with youths at risk for psychosis found that although the groups clearly had differing early developmental and treatment histories, there were no differences in schizotypal traits, disorganization, and general prodromal symptoms. In that study, 78% of the MCDD group met criteria for at-risk mental state. The authors concluded that children with MCDD are at high risk for psychosis later in life.

 

What is already known about autism and schizophrenia?

. Although autism has long been recognized as a separate diagnostic entity from schizophrenia, both disorders share clinical features. Childhood-onset schizophrenia (COS), considered a rare and severe form of schizophrenia, frequently presents with premorbid developmental abnormalities. This prepsychotic developmental disorder includes deficits in communication, social relatedness, and motor development, similar to those seen in autism spectrum disorders (ASD).

 

What new information does this article add?

.This article highlights the biological and clinical links between the two disorders, reviewing shared genetics, brain changes, and similarities and differences in clinical presentations.

 

What are the implications for psychiatric practice?

.Autism and schizophrenia may present as 2 separate disorders that need to be differentiated, or as comorbid conditions. It is important to remember that some individuals may have both COS and ASD, which has implications when designing appropriate biopsychosocial interventions. Adult psychiatrists may benefit from additional training in the diagnosis of ASD in adults, whereas child psychiatrists may benefit from increased comfort with identifying primary psychotic symptoms in autistic youth.

 

Case Vignette

George is a 14-year-old boy who first presented to Dr Frazier at age 8 with a diagnosis of ASD. The diagnosis had initially been made when George was 27 months old and had been reconfirmed by numerous well-regarded autism experts over the years. George had received the usual autism-specific services, and although he made gains, he continued to present with atypical behaviors. George was referred to Dr Frazier because of an increase in the intensity and frequency of unusual and disturbing preoccupations that often had a morbid theme. Those who worked with him had difficulty in getting him off of these disturbing topics.

George also had unusual behaviors and mood-regulation difficulties. When he first presented to the clinic, he was disinhibited, emotionally unstable, and talked at length about his “other world.” His thoughts were loosely connected and he spoke about the friends in his other world who were talking to him. Initially, these friends were humming to him or saying hello. Because of a history of at least 1 depressive episode and what appeared to be more of a chronic euphoric state with affective lability, George was given a provisional comorbid diagnosis of bipolar disorder with psychotic features. Over the ensuing years, despite a number of medication trials including atypical antipsychotics and mood stabilizers, he became tortured by more persistent auditory hallucinations. “She” was particularly disturbing to him and he wanted her to go away.

George’s affective instability continued, but his thought disorder and psychosis have been the most enduring symptoms, even in the absence of mood dysregulation. His comorbid diagnosis was changed to schizoaffective disorder and, more recently, to schizophrenia. He is currently taking a typical antipsychotic. His thoughts are more linear, he rarely talks about “she,” and he is much more able to engage in his schoolwork.

Although George’s psychotic symptoms are well controlled by the medication, symptoms of ASD persist, including poor eye contact, ongoing failure to develop appropriate peer relationships, inability to sustain a conversation with others, encompassing preoccupation with restricted patterns of interest, stereotypies, and repetitive motor mannerisms. These symptoms, present since early childhood, predated his symptoms of psychosis and continue to require the support of autism-specific services.

 

Genetics

Although epidemiological studies of the genetic relationship between autism and schizophrenia are deficient, evidence does exist for shared genetic factors.20 As with the majority of psychiatric disorders and other common conditions, genetic complexity is compounded by phenotypic complexity. Copy number variant and rare allele studies have found a relationship between autism and point and structural mutations in neurologins, neurexins, and related genes.7

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