Identifying endophenotypes for schizophrenia among at-risk samples has become a critical area of investigation that has the potential to direct early detection and intervention programs.39
Neurobiologically based impairments in cognition have been promising candidates for reliable endophenotypes of the disorder.11
Unfortunately, while individuals who ultimately develop schizophrenia demonstrate significant impairments in both social cognitive and neurocognitive function,1,40
the majority of research on cognitive risk markers for schizophrenia has focused exclusively on neurocognitive domains. As such, little is known about the degree to which impairments in social cognition are present among individuals at risk for the disorder, beyond the well-documented neurocognitive deficits experienced by the population,12
or whether such premorbid deficits are associated with the increased prodromal symptoms that can mark the transition to psychosis.
This research investigated the presence of social cognitive impairments in facial emotion recognition among at-risk relatives of patients with schizophrenia and healthy controls. Results indicated that individuals at familial high risk for schizophrenia were significantly more likely to overattribute emotions to neutral faces and predominantly misinterpreted such faces as negatively valenced. This deficit in the emotional interpretation of neutral faces persisted after adjusting for overall deficits in neurocognition and was significantly related to both prodromal positive symptoms and general psychopathology, whereas neurocognitive impairment was only associated with prodromal symptoms of disorganization. In addition, significant degradations in the speed with which at-risk individuals completed emotion recognition tasks were observed, regardless of the valence of the stimuli, and reduced reaction time in completing neutral facial recognition tasks was significantly associated with increased prodromal general psychopathological symptoms. The observed deficits in processing speed during emotion recognition tasks were also present after adjusting for overall neurocognitive dysfunction.
These findings support a social cognitive deficit in emotion recognition as a potential unique endophenotype and risk marker for schizophrenia. That at-risk individuals tended to show a general overattribution bias toward labeling neutral faces as negative and that this bias was associated with prodromal symptomatology are particularly interesting given theoretical and empirical work on the formation of positive symptoms. For example, prominent models of delusion formation suggest that individuals with persecutory delusions and paranoia are prone to selectively attending to negative stimuli.16
Such a bias has been proposed as stemming from social cognitive deficits in the processing and interpretation of social stimuli, which has received support from both the interpersonal attribution and theory of mind literature.41
Further, investigators employing the same emotion recognition paradigm used in this study have shown that patients with chronic schizophrenia also exhibit a negative overattribution bias toward neutral faces,26
suggesting that negative interpretations of neutral stimuli may be generally characteristic of those with positive symptoms. The findings of this research support these investigations and indicate that such deficits in emotion perception may be an early precursor to the development of positive symptoms and ultimately schizophrenia, as the frequent misinterpretations of benign social stimuli as negative observed in this sample would seem likely to lead to the kind of information processing biases that Bentall et al16
describe in delusion formation. In addition to contributing to the development of positive symptoms, it seems plausible that the misinterpretation of neutral faces could have sizable functional consequences on social behavior as well. For example, negative displays of affect usually cue individuals to avoid social interaction, and if there is a negative overattribution bias toward even neutral faces, it is likely that significant social withdrawal and avoidance could result, as is common in schizophrenia. Subsequent studies are needed to further examine the predictive strength of these emotion recognition biases to the development of schizophrenia and related disorders in order to determine whether such deficits are truly early prognostic markers of those who will develop positive symptomatology and psychosis.
It is also interesting that the social cognitive and neurocognitive measures used in this research were largely independent. As discussed above, social cognitive deficits in the perception of neutral faces all persisted after adjusting for a significant neurocognitive performance deficit. Further, emotion recognition and individual neurocognitive measures showed few significant relations, and all were small in magnitude.42
Such findings largely support research with patients with schizophrenia indicating that neurocognitive and social cognitive impairments appear to be separate but related constructs, both of which warrant investigation.15,43
The absence of more sizable relations with neurocognitive function in this at-risk sample may be specific to either this population or the measure of emotion recognition used. It is possible that emotion recognition and general cognitive impairments may become more closely related as the phenotype of schizophrenia emerges, as studies of patients with chronic schizophrenia using similar measures have shown stronger relations between these constructs.44
Unfortunately, to date, few studies have examined social cognitive impairments as potential endophenotypes and risk markers for schizophrenia in at-risk samples, and to our knowledge, no investigation has examined both neurocognitive and social cognitive impairments within a single study. Clearly more work in this area is needed, as a number of deficits in social cognition beyond emotion recognition have been documented in schizophrenia.40
However, the degree to which deficits beyond emotion recognition are present in at-risk samples or uniquely predictive of the development of schizophrenia is largely unknown. Subsequent studies will need to broaden social cognitive assessment to additional domains, such as perspective taking, emotion management, interpersonal attribution, and theory of mind and employ longitudinal designs to examine the stability and predictive utility of deficits in these areas.
Finally, it is important to note that while this research suggests that social cognitive impairments in emotion recognition may be a potential endophenotype for schizophrenia, several limitations preclude firm conclusions regarding the endophenotypic status of such deficits. To begin, this investigation was not able to reliably examine heritability estimates across individuals with different genetic loadings for schizophrenia (eg, multiplex vs simplex families, first-degree vs second-degree relatives) due to its modest sample size and primary inclusion of first-degree relatives. In addition, the use of a single measure of emotion recognition to assess social cognition makes it difficult to determine whether broad impairments in other social cognitive domains (eg, perspective taking, social cue recognition, emotion regulation) exist in at-risk relatives or whether impairments are circumscribed to emotion recognition. The young sample of at-risk relatives studied in this research also indicates a need for further study as these individuals age and with older at-risk samples in order to identify the generalizability of these findings to older individuals. Continued exploration of these deficits among individuals at clinical high risk for the disorder, as done by Addington et al,45
will be particularly important in future studies, as this study focused only on individuals at familial risk for the disorder, few of whom met clinical high-risk criteria. In addition, this cross-sectional study provides no information about the stability or predictive power of social cognitive deficits toward schizophrenia development in at-risk samples. Further, familial high-risk and healthy control individuals were not matched in this research for IQ, although analyses adjusting for differences in neurocognitive ability (which included IQ) suggested that the impairments in social cognition seen in at-risk relatives cannot be accounted for by a general neurocognitive deficit. Finally, the degree to which these deficits are unique to individuals who will develop schizophrenia vs those who develop another disorder remains unanswered. Rather, by showing an increased prevalence of this deficit in unaffected individuals, our data represent a first step in this regard.
Carefully designed family studies with adequate numbers of individuals with diverse ages and different genetic loadings for schizophrenia that incorporate longitudinal designs, other psychiatric populations, broader measures of social cognition, and both molecular and neurobiologic measures are needed to verify the potential of social cognitive deficits as true endophenotypes for schizophrenia. Such studies are likely to not only provide critical information about the pathophysiology of the disorder but also point to promising directions for early intervention and prevention programs. Our recent work with cognitive enhancement therapy,46
a social and nonsocial cognitive rehabilitation approach for schizophrenia, has already yielded very promising preliminary results when applied early in the illness.47
If social cognitive impairments are strong precursors to schizophrenia development, the application of such approaches as cognitive enhancement therapy to at-risk individuals may be particularly effective for altering the deteriorative course of the disorder.