Abstract
OBJECTIVE: Fragile X (FraX) syndrome is caused by mutations of the FraX mental retardation-1 gene-a gene responsible for producing FraX mental retardation protein. The neurocognitive phenotype associated with FraX in female subjects includes increased risk for emotional disorders including social anxiety, depression, and attention deficit. Here, the authors investigated the neurobiological systems underlying emotion attribution in female subjects with FraX syndrome. METHOD: While undergoing functional magnetic resonance imaging, 10 high-functioning female subjects with FraX syndrome and 10 typically developing (TD) female subjects were presented with photographs of happy, sad, and neutral faces and instructed to determine the facial emotion. RESULTS: No significant group differences were found for the recognition of happy faces, although the FraX group showed a trend toward a significant difference for the recognition of sad faces and significantly poorer recognition of neutral faces. Controlling for between-group differences in IQ and performance accuracy, the TD group had greater activation than the FraX group in the anterior cingulate cortex (ACC) for neutral faces compared with scrambled faces and the caudate for sad faces compared with scrambled faces (but not for sad faces compared with neutral faces). In the FraX group, FraX mental retardation protein levels positively correlated with activation in the dorsal ACC for neutral, happy, and sad faces when independently compared with scrambled faces. Significantly greater negative correlation between IQ and insula activation for neutral faces relative to scrambled faces was observed in the FraX group compared with the TD group. Significantly greater positive correlation between IQ and ACC activation for neutral faces relative to scrambled faces was observed in the TD group compared with the FraX group. CONCLUSIONS: Although emotion recognition is generally spared in FraX syndrome, the emotion circuit (i.e., ACC, caudate, insula) that modulates emotional responses to facial stimuli may be disrupted.