Results of this study indicate that individuals with autism spectrum disorders and individuals with paranoid schizophrenia show significant reductions in neural activation compared to control and NP-SCZ individuals during tasks of complex social cognition. Reduced activation was evident in the amygdala, fusiform face area, and the ventrolateral prefrontal cortex. Reductions in amygdala and FFA activation in ASD and P-SCZ are consistent with several studies that have investigated these disorders independently, although primarily without examining schizophrenia subtypes, and while utilizing more basic tasks of social cognition such as viewing faces and recognizing emotion (Critchley et al., 2000
, Hempel et al., 2003
; Piggot et al., 2004
; Quintana et al., 2003
; note that Piggot et al., (2004
) found reduced FG activation in ASD, but no difference in amygdala activation between controls and individuals with ASD). Overlapping reductions in the social cognitive network, across two distinct disorders, therefore suggest that social cognitive impairment may be subserved by specific neural abnormalities and that this pattern of neural abnormalities may be deficit specific
rather than disorder specific
. In other words, it is possible that any individual who shows specific social cognitive deficits may show the same pattern of neural abnormalities regardless of clinical diagnosis. Additionally, the lack of reduced activation in P-SCZ and ASD during age judgments suggests that reduced neural activity for complex social judgments cannot be attributed to overall reductions in activation, generalized deficits in social information processing, a failure to view the stimuli, or failure to engage in the task.
Additionally, exploratory analyses suggest that unlike control participants, and to lesser extent NP-SCZ participants, ASD and P-SCZ failed to show greater activation in face processing/social cognitive neural regions during trustworthiness, as compared to age, judgments. Although this finding needs to be interpreted cautiously as trustworthiness judgments always preceded age judgments, the lack of neural modulation seen in P-SCZ and ASD may suggest that these individuals are processing all judgments of faces in a similar manner, irrespective of their social nature or complexity. Given that the amygdala has been linked to associating stimuli with social and emotional value (Adolphs, 2001
), it is possible that individuals with ASD and P-SCZ are not assigning appropriate emotional significance to facial stimuli when asked to make a complex social judgment. This may, in turn, contribute to social dysfunction. Though speculative, these findings suggest a mechanism for social impairments in schizophrenia and ASD that warrants further research.
It should also be noted that the ASD group did not differ from controls on behavioral ratings of faces despite reduced activation of the amygdala, FFA, and VLPFC. While somewhat counterintuitive, this may be explained by the fact that the ASD group showed normative STS activation. Such differential activation across regions within the social cognitive network is consistent with a systemizing strategy in which individuals with ASD use feature- and rule-based strategies for processing faces (Ashwin et al., 2007
). Thus, these findings may provide further evidence that individuals with ASD do not assign emotional significance to faces.
Interestingly, both ASD and P-SCZ showed comparably increased levels of paranoid ideation. Similar levels of paranoia may explain the observed neural and behavioral similarities in this study. As noted previously, behavioral comparisons between schizophrenia and autism have yielded few to no differences in social cognitive performance when the schizophrenia group shows prominent paranoid symptoms (Craig et al., 2004
; Pilowsky et al., 2000
; for an exception see Bolte and Poustka (2003
); however in this study the symptom presentation of the schizophrenia sample was not detailed, and an effort to recruit only individuals with paranoid symptoms was not reported). These results underscore the importance of a symptom-based approach in the study of clinical disorders. As applied here, a symptom based approach suggests that a long-standing paranoid perceptual process may serve as the mechanism for the equifinality found between the two disorders in social cognitive neural activation.
The present study also extends previous work by highlighting an important distinction between schizophrenia subgroups. More normative activation of social cognitive regions for non-paranoid relative to paranoid individuals is consistent with previous work showing normal levels of amygdala activation in non-paranoid schizophrenia during passive viewing of emotional facial expressions (Williams et al., 2004
) and may help explain why individuals with non-paranoid schizophrenia rated faces similarly to healthy individuals. The finding that this differentiation between subgroups is also present during complex social information processing and in other regions implicated in social cognition underscores the vital importance of symptoms and sub-typing for fully understanding social cognitive deficits in schizophrenia.
Although the present study provides new data regarding mechanisms of impaired social cognition in two distinct clinical populations, a number of issues require further clarification. First, the effect of medication was not addressed here, as all SCZ individuals were taking neuroleptic medication at the time of the study and it is possible that type of medication or duration of neuroleptic exposure may influence neural activation. It is unlikely however that our results were due solely to medication effects given the SCZ groups did not differ in medication dosage but did differ in neural activity. Furthermore, ASD individuals were not taking neuroleptics but showed similar neural patterns to the P-SCZ group. Second, while the P-SCZ and ASD groups reported a similar amount of paranoid ideation, we are unable to determine if these symptoms are qualitatively similar, and thus future work will be necessary to clarify this interesting overlap between disorders. Third, the trustworthiness vs. age results are complicated by the fact that these conditions were not counterbalanced. It is possible that patients may have continued to assess faces for trustworthiness during the age task; however, this seems unlikely as there were no behavioral differences, and more importantly, no differences in reaction times, between the groups on age judgments. If the clinical groups were continuing to process trustworthiness in addition to age, this should have been reflected in longer reaction times than those seen in the trustworthiness task. Fourth, while 48 individuals were examined, the size of each group was relatively small and only right handed male participants were included. These factors limit the generalizability of the results (e.g. to females and individuals who are left handed or lack handedness, which may be more common in autism (Cornish & McManus, 1996
)) and suggest that replication with a more diverse sample is required. Finally, given recent work demonstrating that neural activation is related to how individuals visually scan face stimuli (Dalton et al., 2005
), it is possible that our results may in part reflect abnormal visual face scanning in the clinical groups. Here, we investigated the natural viewing of faces by these groups, but future fMRI work should employ concurrent eye-tracking to investigate these effects.