Background
Patients with 22q11.2 deletion syndrome (22q11DS), a frequent neurogenetic condition occurring in up to 1:1000 pregnancies [
1], are characterized by an increased risk of developing schizophrenia in adolescence and early adulthood (i.e., up to 20% of risk [
2]). Across a broader age range, individuals affected by this genetic condition also experience higher schizotypal traits [
2], which are considered as one of the possible phenotypic expressions of latent vulnerability to psychosis (i.e., schizotypy) [
3]. Furthermore, impaired functioning, especially in the social domain, constitutes one of the hallmarks of the 22q11DS clinical phenotype [
4,
5]. A better understanding of the mechanisms underlying schizotypal traits and social functioning is crucial in order to improve clinical interventions in this population. Social cognition refers to the way people make sense of others’ behavior and has been conceptualized as a factor contributing to social impairments and psychotic symptoms in patients with schizophrenia (e.g., [
6]). Social cognition is a multifaceted construct, in which affective (i.e., ability to perceive and understand others’ emotional states) and cognitive (i.e., ability to infer others’ beliefs and intentions or theory of mind (ToM) and its related processes such as perspective-taking) dimensions can be distinguished [
7]. Although these abilities are conceptualized as distinct processes, they are not completely independent and interact in many ways to produce adapted social behaviors [
8].
The affective dimension of social cognition has been particularly studied in the field of 22q11DS. Indeed, several studies found that patients with 22q11DS were impaired in their ability to recognize facial emotional expressions [
5,
9‐
12], or infer emotions of characters presented in short stories [
13]. Gur et al. recently showed that the affective facet of social cognition was more impaired than expected based on intellectual disability level and that it followed an atypical developmental trajectory over time [
11]. In their study, the authors computed developmental charts for several cognitive domains including social cognition (composite measure covering emotion identification, emotion intensity differentiation, and age differentiation) using the performance of typically developing individuals aged 8 to 21 years as the normative group. The chronological age of patients with 22q11DS was then compared to a developmental age (reflecting the difference between the score obtained by the participants and the norm) computed for each cognitive domain. These analyses showed that patients with 22q11DS steadily lagged behind the normative group on the social cognition composite score after age 8, but the gap increased and widened after age 14. However, a recent study showed that the recognition of facial emotions was relatively unimpaired in individuals with 22q11DS compared to typically developing controls when dynamic pictures of faces were presented [
14]. Shashi et al. also reported similar performance in the recognition of vocal emotional expressions compared to the control group [
5]. Altogether, these findings suggest that individuals with 22q11DS may be characterized by alterations of the affective dimension of social cognition. In particular, this seems to be the case when it is assessed in the visual modality and using static stimuli, which could be related to the use of atypical gaze patterns during visual exploration [
9,
14‐
17].
Similar to its affective counterpart, the cognitive facet of social cognition was also found to be impaired in children and adolescents with 22q11DS in studies [
12,
18] that used ToM tasks such as the Awareness of Social Inference Test (TASIT; [
19]) or the Animation Task (see [
20]). However, one study using false-belief tasks observed that ToM abilities had a delayed development in 22q11DS rather than long-lasting deficits. According to Campbell et al., these incongruent findings may be due to the fact that false-belief tasks rely strongly on verbal comprehension, whereas the remaining ToM paradigms used visual material (sometimes in combination with verbal narratives) [
13]. In addition, a ceiling effect in the control group for some of the false-belief tasks may have prevented the detection of significant group differences.
Although findings are generally indicative of significant impairments in the affective and cognitive facets of social cognition in patients with 22q11DS, these domains have never been investigated simultaneously within the same group of participants. This would help better understand whether patients with 22q11DS tend to have a global deficit in the area of social cognition or whether specific profiles can be defined. Furthermore, little is known about the association between these two processes and psychotic symptoms or social difficulties in this population. One study found that the cognitive dimension of social cognition was significantly associated with parent ratings of social competence [
10], but this finding was not replicated in a subsequent study using a different task [
13]. Additionally, Jalbrzikowski et al. observed that lower scores on the TASIT were associated with positive symptom severity in patients with 22q11DS but were unrelated to negative symptoms [
12]. Finally, clinical and functional correlates of the affective dimension of social cognition have rarely been examined. To date, only one study has examined whether affective ToM contributed to social skills but did not find any significant association [
5].
In the present study, the performance of adolescents and young adults with 22q11DS was examined in two tasks measuring affective and cognitive facets of social cognition. A classical emotion recognition paradigm was chosen to measure the affective facet, and a perspective-taking paradigm (an adapted version of the Director task developed by [
21]) was used to assess the cognitive facet. The latter task was chosen for its appropriate use across a broad age range, including adulthood. Indeed, it was designed to avoid ceiling effects that are typically observed when adults perform classical ToM or perspective-taking tasks. In line with previous findings in the field of social cognition, we expected patients with 22q11DS to score significantly lower on both tasks compared to a group of typically developing individuals. Given the inter-related nature of the two processes [
8], we also expected to observe significant associations between the affective and the cognitive facets in both groups of participants. Finally, in order to improve our knowledge of increased social dysfunction and psychotic symptoms in 22q11DS and typically developing individuals, our last analyses were performed in each group separately. Specifically, we examined whether the performance (indexed by ACC) and/or the efficiency (indexed by RT) to both social cognitive tasks were related to the Schizotypal Personality Questionnaire (SPQ) scores and/or to the Vineland Adaptive Behavior Scales (VABS). Importantly, the literature holds that schizotypal traits assessed at a behavioral level may serve as distal risk marker for psychosis (for a review, see [
22]).
Discussion
The present study employed two experimental measures to investigate the cognitive and affective dimensions of social cognition in a sample of individuals with 22q11DS compared to healthy controls. We also examined the extent to which both socio-cognitive dimensions were associated to self-reported schizotypal traits and social functioning. Four main observations summarize the current study: (1) participants with 22q11DS had lower accuracy scores but comparable response times compared to healthy controls on (a) the facial emotion recognition task; (b) the perspective-taking paradigm; (2) the two socio-cognitive dimensions investigated here were correlated in healthy controls; (3) the response time scores in the perspective-taking condition of the director task were associated to positive schizotypal traits in healthy control participants; and (4) the response time scores in the perspective-taking condition of the director task which were marginally associated to negative and disorganized schizotypal traits in participants with 22q11DS. These results will be discussed in relation to the existing body of empirical and conceptual literature.
As expected, individuals with 22q11DS showed lower abilities than healthy controls to correctly recognize facial emotions, which are consistent with previous findings in the literature [
5,
10‐
13]. Atypical behavioral [
9,
14,
15] and cerebral [
34,
35] processing of faces in 22q11DS, as well as structural alterations in the brain regions involved in facial emotion recognition [
36,
37], may contribute to the current results. Indeed, eye-tracking studies have consistently shown different patterns of visual exploration during face-processing tasks involving neutral or emotional stimuli in individuals 22q11DS [
14,
15]. Compared to typical and idiopathic developmentally delayed control groups, patients with 22q11DS were shown to spend less time on the eyes and more time on the mouth [
15] or the nose [
14] when examining faces. Furthermore, abnormal responses to faces have been observed in patients with 22q11DS, which include a lack of normal face selectivity in the fusiform gyrus [
34], and a reduced activity compared to controls in brain regions involved in emotion processing during the presentation of diverse emotions at varying intensities [
35]. Of note, a recent study reported similar accuracy scores between participants with 22q11DS and healthy controls during an emotion recognition paradigm [
14]. The sample and task used by Fanchini et al. may partially explain these contradictory findings. Indeed, emotion recognition was assessed with a dynamic paradigm in a sample of children with 22q11DS, while the data reported here were collected using static stimuli in a group of patients with 22q11DS of a broader age range. Thus, emotion recognition difficulties may appear later in the development and/or be highly influenced by the type of stimuli. Still, these hypotheses remain speculative and should be addressed in further studies that directly compare both tasks in multiple age groups of patients with 22q11DS.
In addition to impairments in the affective dimension of social cognition, participants with 22q11DS struggled to reason according to the perspective of another person in an online communication task, in which they were requested to move objects that can be seen by themselves and their interlocutor. These results are in line with and extend available data on theory of mind (ToM) impairments in this syndrome [
10,
12,
13,
18]. This paradigm focuses on a specific component of cognitive ToM (i.e., perspective-taking abilities) that has never been investigated in 22q11DS. It should be noted that although participants with 22q11DS made an increased number of errors compared to the control group, the mean accuracy score in both groups was low. This is consistent with recent findings using the same paradigm in adolescents from the general population that show an improvement of perspective-taking abilities during adolescence and into early adulthood [
21]. Impaired performance on this task has been explained by a marked egocentric interference of the self-perspective (i.e., the selection of the correct object from our own perspective and not the one that fits the director’s perspective) [
38]. In participants with 22q11DS, perspective-taking abilities might have been influenced by higher-order cognitive difficulties, as perspective-taking was shown to engage working memory or cognitive control processes (e.g., [
39]). This interpretation is in line with the fact that participants with 22q11.2DS encountered important difficulties in the no-director condition and that executive functioning represents one of the most affected domains of the 22q11DS phenotype. Indeed, a recent study showed that certain executive functions followed an atypical trajectory and that executive deficits were especially pronounced during adolescence [
40]. The association between executive functioning and social cognition has been further pointed out at a cerebral level; the brain regions that sustain executive processes are highly overlapping with the neural networks referred to as the “social brain” [
41].
Taken together, the results presented so far suggest that individuals with 22q11DS exhibit difficulties in inferring both cognitive and affective mental states to others, regardless of the type of cue. Indeed, individuals with 22q11DS show similar deficits when they have to attribute an emotional state to someone else based on visible cues (i.e., facial features in the emotion recognition task) and when they have to put themselves in the director’s shoes and use the director’s perspective to resolve the task without manifest clues. In future studies, it might be interesting to disentangle the variables that contribute to the shared variance between the two socio-cognitive processes. Moreover, as social cognition is a complex and multi-dimensional process, forthcoming works are needed to cover other aspects of that higher order ability. We state here that the next step could be, for instance, to replicate the current results with more naturalistic tasks that also extend the range of tested emotions and the modalities of testing (e.g., including auditory processes).
Because two core aspects of the 22q11DS clinical phenotype, namely, schizotypal symptoms and impaired socialization [
4,
5], have been related to socio-cognitive impairments in various populations [
6] and because these different domains have been tied to overlapping neural networks, our last aim was to examine the associations between these clinical manifestations and the socio-cognitive tasks in both groups of participants. In line with the previous findings [
42], participants with 22q11DS were characterized by higher levels of negative symptoms and impaired adaptive social functioning. In the context of this study, the presence of autism spectrum disorder (ASD) or autism traits was not formally assessed. Given that general population studies have shown a significant association between negative schizotypy and autism traits [
43,
44], we cannot exclude that the elevated negative schizotypy score observed in the present study would have some link to the potential increased prevalence of patients meeting ASD criteria. However, the question deserves a detailed protocol, using all the appropriate measures that can tackle the issue with respect for its complexity. Similarly, the influence of other clinical diagnoses was not directly investigated. Given the high comorbidity existing between anxiety, mood, and psychotic disorders in 22q11DS [
4], this should be addressed in future studies including larger samples. Notwithstanding, we crucially believe that potential associations with other clinical dimensions could inflate the strength of the correlations but would not change our conclusions regarding the present findings.
An association between the degree of schizotypal traits (positive dimension) and the efficiency of perspective-taking processes was observed in typically developing participants, which supports previous broader evidence of social cognition deficits along the psychosis continuum [
45,
46]. However, contrary to our hypothesis, schizotypal symptoms and socialization skills were poorly related to the affective and cognitive facets of social cognition in participants with 22q11DS. We were only able to highlight a marginally significant association between slower response times in the perspective-taking task and higher levels of negative and disorganized symptoms, as measured by the SPQ. Of note, associations with all three dimensions of the SPQ became significant when participants under antipsychotic medication were excluded from the analyses.
Regarding the association between schizotypal traits and response times in the director condition, this result was less expected, in light of the absence of difference between the two groups on this variable. This result must be replicated in future studies before any conclusions could be drawn. Yet, statistical and conceptual hypotheses can be put forward to illuminate our data. On the one hand, because the mean accuracy score in the director condition was low, it is probable that RT are more sensitive to individual differences given they have higher variance than ACC scores. On the other hand and given that the RT scores were only calculated for correct items, our result suggests that in PT, the capacity to take the perspective of another person may be less important to consider than the efficiency of that ability. Plausibly, the total variance of socio-cognitive abilities could be explained by partially independent components of speed and accuracy associated to, at least partially, distinct variables. The importance of separating speed and accuracy has been widely proven in intelligence research [
47]. To the best of our knowledge, whether a similar latent model might underlie perspective-taking capacities still needs to be established; this should be considered in future studies. Finally, another point that might deserve attention is that social cognitive processes can only fully develop over time. Previous studies have shown that adults are more accurate than youths and children but also tend to take more time (e.g., [
21]). Thus, accuracy and response time might be differentially sensitive to typical (e.g., age) and atypical (e.g., schizotypal traits) developmental processes.
Concerning the lack of relation with accuracy scores, a series of prior empirical work has similarly failed to corroborate the theoretical argument that socio-cognitive skills underlie social difficulties and psychiatric symptoms in daily life [
48]. Measurement and sample issues may account for the lack of meaningful observations reported here. Indeed, the current study includes experimental tasks that isolate specific socio-cognitive mechanisms rather than encompassing the whole complexity of interpersonal relationships. Of note, both samples included a limited number of participants, implying that some findings might have been significant if tested in bigger groups. As such, measurement limitation may also have contributed to a lack of sufficient power to detect statistically significant within-group associations. Therefore, future work should address the question of cognitive and affective facets of social cognition in 22q11DS in larger samples. Despite these limitations, findings related to response times in the perspective-taking task are promising, especially because this paradigm was designed to bypass the limitations of classical cognitive ToM and perspective-taking measures and is viewed as a better indicator of perspective-taking in real life. Indeed, one of the major criticisms of classical ToM and perspective-taking paradigms is that the participants only play an observer role and have to infer mental content to individuals with whom they are not interacting [
49]. “Hence, future studies should replicate these results in a larger sample and attempt to better explain the contribution of perspective-taking impairments in the emergence of psychotic symptoms in 22q11DS, thereby informing future evidence-based treatment”.