Review article
Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder

https://doi.org/10.1016/j.neubiorev.2016.12.036Get rights and content

Highlights

  • Meta-analysis of social cognition in epilepsy and relatives of people with autism.

  • People with epilepsy (TLE and other epilepsies) have a social cognition deficit.

  • The social cognition deficit is less severe in relatives of people with autism.

  • Reduced social cognition is associated with an earlier age at epilepsy onset.

  • The findings suggest shared neurobiological mechanisms between epilepsy and autism.

Abstract

Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX–XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N = 1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p < 0.001), but only reduced ToM in ASD-relatives (p < 0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability.

Section snippets

The association between epilepsy and autism spectrum disorder

Epilepsy is a disorder characterised by unprovoked seizures, with diagnosis requiring at least one unprovoked seizure and high risk for another (Fisher et al., 2014). The reported prevalence of epilepsy ranges from 0.2–2% (M = 1%; Bell et al., 2014). Age at onset is typically in childhood or late adulthood, but first seizures can occur at any age (Cockerell et al., 1995).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by persistent impairment in reciprocal social

Literature search

We conducted a systematic search of the published literature available through the PubMed, PsycINFO, and Current Contents Connect databases. The key words entered to retrieve relevant reports are listed in Table 2. We evaluated the titles and abstracts of the retrieved reports to find those that examined FER or ToM in our target groups of PWE and ASD-relatives. The literature search was completed in August 2014 and included peer-reviewed journal articles; article abstracts; conference and

Results

Table 5 provides an overview of the demographic and clinical characteristics of the participants from the meta-analysed studies. Individuals with epilepsy were older and had lower IQ than relatives of individuals with ASD across studies of FER and of ToM (t-test P-values <0.001). In FER studies, PWE had a greater ratio of males to females than was observed in ASD-relatives (Chi-square test P-value < 0.001). There was no difference in the sex ratio of patients with epilepsy and ASD-relatives from

Discussion

In this meta-analysis, we assessed the evidence for expression of BAP features, specifically deficits in FER and ToM in the absence of ID, in PWE and ASD-relatives compared to controls. We included 31 reports of PWE and 22 of ASD-relatives, providing data on 1449 PWE and 1295 ASD-relatives. As hypothesised, we found that FER and ToM were reduced in PWE compared to controls. These findings were robust to the exclusion of outlying studies of large effect and to publication bias. FER and ToM

Conclusion

Our results, based on data from over 1000 epilepsy patients and ASD-relatives, show that PWE, including those with non-TLE, have reduced FER and ToM compared to controls and that the social cognition deficit in PWE is more severe than that in ASD-relatives. Moreover, earlier age at epilepsy onset and longer epilepsy duration are associated with poorer FER and ToM. Based on these patterns of FER and ToM deficits in PWE, we have presented a dual-strike model. It suggests that social cognition

Acknowledgements

We kindly thank the authors who responded to our requests for additional data as well as Dr. Sue Finch from The University of Melbourne’s Statistical Consulting Centre for providing statistical advice.

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