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Autism and Schizophrenia: Page 2 of 2

Autism and Schizophrenia: Page 2 of 2

There have also been reports that implicate the neurexin family in schizophrenia. Neurologins are a family of postsynaptic proteins that bind transsynaptically to neurexins, which are presynaptic proteins that seem necessary for both excitatory and inhibitory synaptogenesis and synapse maturation. This fits with the neurodevelopmental insult and imbalance in excitatory and inhibitory transmission hypothesis for both autism and schizophrenia.20

Specific deletions associated with schizophrenia include 22q11.2, 1q21.1, and 15q13.3, which have been found to be associated with autism, attention-deficit disorder, and mental retardation.20 In individuals with velocardiofacial syndrome (chromosome 22q11), rates of ASD and psychosis are higher.21 Similarly, 16p11.2 microdeletions or microduplications have been reported in 1% of cases of autism and in 2% of the NIMH COS cohort.22-24 These copy number variants confer a risk for a range of neurodevelopmental phenotypes that include autism and schizophrenia.20 Although there have not been systemic comparisons of genome-wide association studies for autism and schizophrenia, some functional links have been reported at voltage-gated calcium channel genes, which are integral to presynaptic function and plasticity, across phenotypes.20

Brain changes

Both autism and schizophrenia have accelerated trajectories of brain development around the age of symptom onset: those with autism have an acceleration or brain overgrowth during the first 3 years of life, and those with COS have an acceleration of brain development (pruning) during adolescence.7

Cheung and colleagues25 attempted to quantify brain structural similarities and differences in ASD and schizophrenia using a quantified anatomical likelihood estimation approach to synthesize existing brain imaging datasets. Using this model, they extracted 313 foci from 25 voxel-based studies comprising 660 patients (308 ASD, 352 first-episode schizophrenia) and 801 controls. Those with ASD and schizophrenia had lower gray matter volumes within limbic-striato-thalamic neurocircuitry than did controls. Unique features included lower gray matter volume in the amygdala, caudate, and frontal and medial gyrus for schizophrenia, and lower gray matter volume in the putamen for autism. The researchers concluded that in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms.25


A variety of psychosocial and educational interventions that support children with COS and children with ASD exist to address core deficits in socialization, communication, and behavior and the associated developmental and medical conditions. A thorough description is beyond the scope of this article, however. Atypical antipsychotics are the mainstay of pharmacotherapy for schizophrenia at any age, and they have also been used to manage certain symptoms, particularly irritability, associated with ASD.26-28


Developmental delays are described premorbidly in samples of children and adults with schizophrenia. More recently, the notion that ASD and schizophrenia can present comorbidly in a subset of patients has received further attention in the literature.7,29 Yet our current diagnostic hierarchy implies that the two conditions are distinct.

The differential diagnosis between these disorders and the comorbid diagnoses of the two conditions is often a bit of a quagmire for clinicians. Our program is frequently asked to rule out ASD, schizotypal personality disorder and/or schizophreniform disorder, and first-episode schizophrenia in youths and young adults. We see children with ASD who have emerging psychotic symptoms. In these children, the hallucinations or delusional preoccupations may initially be attributed to the developmental disorder. Conversely, we also see adolescents or young adults with schizophrenia who have a developmental history consistent with ASD (typically higher functioning) and who continue to have comorbid ASD. Yet some have not previously received a diagnosis of ASD. Appropriate identification of comorbid conditions can enhance intervention efforts (eg, autism-related services for those with comorbid ASD and/or use of antipsychotics in patients who have comorbid ASD and a psychotic disorder).

The key take-away point is that there are some individuals who may have both COS and ASD. Adult psychiatrists and mental health professionals would benefit from further training in the diagnosis of ASD in adults, and child mental health professionals would benefit from training in the diagnosis of schizophrenia spectrum disorders in youths. Given the complex symptom profile in youths with schizophrenia spectrum disorders, there tends to be a delay in diagnosis, even when symptoms are present for years.30 In addition, child mental health professionals would benefit from training in more specific identification of primary psychotic disorders in youths with ASD. Finally, care must be provided in an integrative manner—using a biopsychosocial model—for these multicomplex patients and their families.

Systematic long-term follow-up studies that include individuals with ASD and with COS are indicated to further inform the field regarding similarities and differences between autism and schizophrenia. These studies would benefit from the inclusion of genetics and characterization of family members to get a clearer sense of the genotype-phenotype associations and predictors of outcome.



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