Amygdala Function in a Known Genetic Cause of Autism

Background: Amygdala dysfunction has been implicated in autism and is an excellent candidate for study because of its role in response to social stimuli and social behavior regulation.  The amygdala has also been associated with several anxiety disorders.  Anxiety is one of the most significant problems experienced by individuals with autism and is a core feature of fragile X syndrome (FXS), the most common known genetic cause of autism. 
Objectives:

We investigated the relationships between the potentiated startle response, a biobehavioral probe of amygdala function, anxiety symptoms and autistic features in a specific cause of autism.

Methods:

We measured the startle response to auditory stimuli delivered during presentation of happy, fearful, and neutral faces and a non-social scrambled image.  The difference in response magnitude between trial types was calculated.  Anxiety symptoms were measured using the Anxiety, Depression and Mood Screen (ADAMS; Ebsensen et al., 2003), a parent report questionnaire.  Severity of autistic symptoms was evaluated using the Autism Diagnostic Observation Schedule (ADOS; Lord, 2001).

The FXS group consisted of 24 individuals (15 boys and 9 girls) ranging in age from 5 to 25 years (mean: 15, SD: 6) and a mean IQ of 65 (SD:16).  The idiopathic autism group contained 22 boys ranging in age from 12 to 22 years (mean: 17, SD: 3) with a mean IQ of 74 (SD: 23).  The control group was 13 children (5 boys 8 girls) with typical development ranging in age from 4 to 17 years (mean: 11.5 SD: 4) and a mean IQ of 112 (SD: 14).

Results:

The FXS group was significantly less responsive than controls on all trial types other than happy faces, which approached significance.  ADOS scores were positively correlated with responses to all trial types except happy faces.  The FXS and autism groups both scored significantly higher on the ADAMS compared to controls but were not significantly different from each other.  ADAMS scores were positively correlated with ADOS scores in the FXS group but not in the idiopathic autism group.

Conclusions:

The difference in potentiated startle response between the FXS group and the control group suggests abnormal amygdalar function in FXS.  The relationships seen here between anxiety symptoms and severity of autistic symptoms may represent a phenotype specific to autism as caused by FXS.  Data collection is continuing in the autism group.