The Broader Autism Phenotype in Parents of Multiplex Versus Simplex Autism

Background: Previous studies suggest that unaffected first-degree relatives of people with ASC display mild difficulties or superiorities on neuropsychological tasks compared to control groups, reflecting a milder expression of the full clinical phenotype (Baron-Cohen and Hammer, 1997; Happé et al., 2001; Losh et al., 2009; Wheelwright et al., 2010). Some of these studies have suggested that this broader cognitive phenotype is restricted to a subset of genetic relatives (Losh and Piven, 2007; Losh et al. 2009), but few have assessed whether it is restricted to the relatives of multiplex autism families. Phenotypic differences between multiplex and simplex autism parents may indicate that differential genetic mechanisms are operating in these two different kinds of families (Abrahams and Geschwind 2008; Sebat et al. 2007).

Objectives: To explore the broader cognitive phenotype of autism in multiplex vs. simplex parents and controls using a battery of neuropsychological tests assessing social cognition. 

Methods: This study included 3 samples: i) 64 parents of autistic probands from multiplex autism families (32 fathers, 32 mothers); ii) 60 parents of autistic probands from simplex autism families (30 fathers, 30 mothers); and iii) 64 age and education-matched controls (32 males, 32 females). Apart from age and education, multiplex and simplex parents were also matched on verbal IQ and non-verbal IQ. Proband diagnoses were verified using the 3Di developmental, diagnostic and dimensional interview (Skuse et al. 2004) and the Autism Diagnostic Observational Schedule (Lord et al. 2000). Parents and controls were administered a modified version of the Karolinska Directed Emotional Faces Task (KDEF; Lundqvist et al. 1998) and the adult version of the ‘Reading the Mind in the Eyes’ Task (Baron-Cohen et al. 2001) assessing basic and complex emotion recognition respectively. 

Results: Multiplex parents had significantly poorer mentalizing ability than simplex parents; they were significantly less accurate at identifying complex mental states from the eye region of the face (p < 0.05), after controlling for verbal intelligence. Results on the KDEF suggested sex-specific difficulties recognising negative basic emotions in multiplex compared to simplex parents or controls, including sadness in ASC fathers (p < 0.05) and fear in ASC mothers (p < 0.01). There were no significant differences in performance between simplex parents and controls on the emotion perception tasks. 

Conclusions: These results provide support for the hypothesis that differential genetic mechanisms may operate in simplex vs. multiplex autism. Emotion perception and social cognitive difficulties may represent an underlying genetic liability for ASC that aggregates in the first-degree relatives of probands from multiplex autism families.