Impaired recognition of angry, fearful, and emotionless (i.e., neutral) faces is associated with poor social functioning among individuals with schizophrenia disorder (SZ). Limited research evaluates how interventions impact these impairments. Computerized social cognition training can improve overall facial emotion recognition in SZ, but it is unclear whether it improves the aforementioned impairments. We report results from a randomized controlled trial (Trial Registration: NCT02246426) evaluating how computerized social cognition training (SCT) impacts recognition of individual emotions in SZ. Ninety-eight individuals with SZ were randomly assigned to one of two internet-based interventions: SCT or a control condition (computer games without social content) (CON). Participants completed 40 sessions of training over 8-12 weeks. Facial emotion recognition was measured with the Penn ER-40 before training, after 20 sessions, and within 8 weeks of completing 40 sessions. Accuracy and reaction times for each emotion (i.e., anger, fear, happy, neutral, and sad) were analyzed. Linear mixed model analyses and t-tests elucidated intervention effects. A significant Group x Time interaction on accuracy was found favoring the SCT group. Only the SCT group improved recognizing fearful and sad faces; the CON group did not. The SCT group had higher accuracy for neutral recognition than the CON group after training. There was no Group x Time interaction on reaction times. We conclude that, because SCT training improves fear and neutral recognition, it has the potential to improve social functioning in SZ. However, interventions need to be further refined to improve anger recognition and emotion recognition reaction times.

Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen’s d = 0.164) and less optimal structural network configuration than HC (lower global efficiency and clustering coefficient, d = 0.100,0.087, qs <= 0.027). Though no global difference between CHR-T and CHR-NT, network distinctiveness of the frontal and temporal surface area networks was higher in CHR-T than CHR-NT (d = 0.223,0.237) and HC (d = 0.208,0.219) (qs < 0.001). Network distinctiveness of the frontal cortical thickness network was lower in CHR-T (d = 0.218, q < 0.001) than CHR-NT and HC (d = 0.165, q < 0.001). Importantly, higher network distinctiveness was associated with worse positive symptoms in CHR-NT (frontal surface area, q = 0.008, R2 = 0.013) and at trend with worse negative symptoms in CHR-T (frontal thickness, q = 0.063, R2 = 0.049). Further, the brief intermittent psychotic syndrome subgroup showed more severe network alterations. Together, brain structural networks inform symptoms and the risk of transition to psychosis in CHR individuals.

Background: Social cognition training (SCT) can improve social cognition deficits in schizophrenia. However, little is known about patterns of response to SCT or individual characteristics that predict response. Methods: 76 adults with schizophrenia randomized to receive 8-12 weeks of remotely-delivered SCT were included in this analysis. Social cognition was measured with a composite of six assessments. Latent class growth analyses identified trajectories of social cognitive response to SCT. Random forest and logistic regression models were trained to predict membership in the trajectory group that showed improvement from baseline measures including symptoms, functioning, motivation, and cognition. Results: Five trajectory groups were identified: Group 1 (29 %) began with slightly above average social cognition, and this ability significantly improved with SCT. Group 2 (9 %) had baseline social cognition approximately one standard deviation above the sample mean and did not improve with training. Groups 3 (18 %) and 4 (36 %) began with average to slightly below-average social cognition and showed non-significant trends toward improvement. Group 5 (8 %) began with social cognition approximately one standard deviation below the sample mean, and experienced significant deterioration in social cognition. The random forest model had the best performance, predicting Group 1 membership with an area under the curve of 0.73 (SD 0.24; 95 % CI [0.51-0.87]). Conclusions: Findings suggest that there are distinct patterns of response to SCT in schizophrenia and that those with slightly above average social cognition at baseline may be most likely to experience gains. Results may inform future research seeking to individualize SCT treatment for schizophrenia.

Motivation in general, and social motivation in particular are important for interpersonal functioning in individuals with schizophrenia. Still, their roles after accounting for social cognition, are not well understood. The sample consisted of 147 patients with schizophrenia. General motivation was measured using the Behavioral inhibition/activation scale (BIS/BAS). Social motivation was measured by Passive social withdrawal and Active social avoidance items from PANSS. Interpersonal functioning was evaluated with Birchwood’s Social Functioning Scale (SFS). We used Exploratory Graph Analysis for network estimation and community detection. Active social avoidance, passive social withdrawal, and social withdrawal/engagement (from SFS) were the most important nodes. In addition, three distinct communities were identified: Social cognition, Social motivation, and Interpersonal functioning. Notably, the BIS and BAS measures of general motivation were not part of any community. BAS showed stronger links to functioning than BIS. Passive social withdrawal was more strongly linked to interpersonal functioning than social cognitive abilities. Results suggest that social motivation, especially social approach, is more closely related to interpersonal functioning in schizophrenia than general motivation. In contrast, we found that general motivation was largely unrelated to social motivation. This pattern highlights the importance of type of motivation for understanding variability in interpersonal difficulties in schizophrenia.

Standard treatments do not address impaired facial emotion processing, which compromises social functioning, in many neuropsychiatric disorders, including schizophrenia. This impairment correlates with abnormal activity and connectivity in neural networks underlying social cognition. Neuroplasticity-based social cognition training has shown promise in improving facial emotion processing and aberrant neural activity, but its impact on connectivity remains unknown. This study evaluates how social cognition training impacts connectivity during facial emotion processing in healthy individuals to better understand its therapeutic potential.

Facial emotion recognition is a key component of social cognition. Impaired facial emotion recognition is tied to poor psychological wellbeing and deficient social functioning. While previous research has demonstrated the potential for social cognition training to improve overall facial emotion recognition, questions remain regarding what aspects of emotion recognition improve. We report results from a randomized controlled trial that evaluates whether computerized social cognition training can improve recognition of distinct facial emotions in healthy participants. This investigation was designed to better understand the therapeutic potential of social cognition training for individuals with neuropsychiatric disorders. Fifty-five healthy adult participants were randomly assigned to an internet-based intervention during which they either completed social cognition training (SCT) or played control computer games (CON) for 10.5 h over 2-3 weeks. Facial emotion recognition was measured with the Penn ER-40, which was conducted before and after training. The following variables were collected and analyzed: facial emotion recognition accuracy for each emotion (i.e., anger, fear, happy, neutral (no emotional expression), and sad), reaction times for each emotion, and response error types (i.e., frequency of an emotion being chosen incorrectly, frequency of an emotion being missed, and frequency of an emotion being confused for another particular emotion). ANOVAs and t-tests were used to elucidate intervention effects both within and between groups. Results showed that the SCT group improved their accuracy for angry and neutral faces. They also improved their reaction times for neutral, fearful, and sad faces. Compared to the CON group, the SCT group had significantly faster reaction times to neutral faces after training. Lastly, the SCT group decreased their tendency to confuse angry faces for no emotional expression and to confuse no emotional expression for sad faces. In contrast, the CON group did not significantly improve their accuracy or reaction times on any emotional expression, and they did not improve their response error types. We conclude that social cognition training can improve recognition of distinct emotions in healthy participants and decrease response error patterns, suggesting it has the potential to improve impaired emotion recognition and social functioning in individuals with facial emotion recognition deficits.

Individuals at clinical high risk (CHR) for psychosis have cognitive and social cognitive deficits associated with functional disability. This RCT investigated whether cognitive and social cognitive training (TCT) in CHR participants would improve their overall cognitive functioning and their social cognitive functioning.

Individuals at clinical high risk (CHR) for psychosis have neurocognitive deficits which are associated with functional disability. Targeted cognitive training (TCT) has been proposed as a therapeutic intervention to improve cognition in CHR individuals. This study investigated whether cognitive and social cognitive training in CHR participants would improve their overall cognitive functioning and their social cognitive functioning.

Social cognition (SC), the mental operations underlying social functioning, are impaired in schizophrenia. Their direct link to functional outcome and illness status have made them an important therapeutic target. However, no effective treatment for these deficits is currently applied as a standard of care. To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia. Here we report the outcomes of a double-blind, controlled, randomized, multi-site clinical trial of SocialVille. Outpatients with schizophrenia were randomized to complete 40 sessions of either SocialVille (N = 55 completers) or active control (computer games; N = 53 completers) from home. The a priori co-primary outcome measures were a social cognitive composite and a functional capacity outcome (UCSD Performance-based Skills Assessment [UPSA-2]). Secondary outcomes included a virtual functional capacity measure (VRFCAT), social functioning, quality of life, and motivation. Linear mixed models revealed a group × time interaction favoring the treatment group for the social cognitive composite (b = 2.81; P < .001) but not for the UPSA-2 measure. Analysis of secondary outcome measures showed significant group × time effects favoring the treatment group on SC and social functioning, on the virtual functional capacity measure and a motivation subscale, although these latter findings were nonsignificant with FDR correction. These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. Such treatments may serve as a cost-effective adjunct to existing psychosocial treatments. Trial Registration: NCT02246426.

Individuals with a schizophrenia-spectrum disorder (SSD) and those at familial high risk (FHR) for SSDs experience social difficulties that are related to neural abnormalities in the network of brain regions recruited during theory of mind (ToM). Prior work with these groups has focused almost exclusively on characterizing the involvement of these regions in ToM. Here, we examine the representational content of these regions using multivariate pattern analysis. We analyzed two previously collected datasets of SSD, FHR and control participants who, while undergoing functional magnetic resonance imaging, completed the false-belief task in which they read stories describing beliefs or physical representations (e.g. photographs). Univariate and multivariate analyses were performed in regions of interest to evaluate group differences in task-based activation and representational content, respectively. Compared to non-SSDs, SSDs showed reduced decoding accuracy for the category of mental states in the right temporo-parietal junction-which was related to false-belief accuracy-and the dorsal medial prefrontal cortex (DMPFC) and reduced involvement of DMPFC for mental state understanding. FHR showed no differences in decoding accuracy or involvement compared to non-FHR. Given prior studies of disrupted neural involvement in FHR and the lack of decoding differences observed here, the onset of illness may involve processes that corrupt how mental state information is represented.

Importance The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, Setting, and Participants In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main Outcomes and Measures Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and Relevance This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Impairments in social cognition (SC) have been linked to a variety of poor outcomes in individuals with schizophrenia, including worse social, community, and occupational functioning as well as higher relapse rates. One important aspect of SC ability is Theory of Mind (ToM), also known as mentalizing, or the ability to understand and make inferences based on others' mental states. ToM is impaired in schizophrenia and, importantly, worse ToM skills are associated with worse social functioning.

Theory of mind (ToM) is a component of social interaction used to understand the behavior of others and one’s own, it can be measured explicitly or implicitly. Computerized targeted social cognitive training (TSCT) interventions have produced improvements in social cognition but changes in explicit versus implicit ToM have not been assessed directly. This study measured changes in implicit and explicit ToM in individuals with schizophrenia to evaluate the effect of TSCT on ToM as well as the relationship in social functioning.

Theory of mind (ToM), the ability to think about the perspectives, beliefs, and feelings of another, develops throughout childhood and adolescence and is an important skill for social interactions. This study examines neural activity in typically developing children during a novel ToM task - the Movie Mentalizing Task- and tests its relations to ToM behavioral performance and social functioning. In this fMRI task, children ages 8-13years (N=25) watched a brief movie clip and were asked to predict a character's mental state after a social interaction. Engaging in the Movie Mentalizing Task activated the ToM neural network. Moreover, greater neural activity in the ToM network, including the superior temporal gyrus and inferior frontal gyrus, was associated with better behavioral performance on independent ToM tasks and was related to better social functioning, though these results do not survive correction for multiple comparisons. Results offer a new affective theory of mind task for children in the scanner that robustly recruits activity in theory of mind regions.

Individuals with schizophrenia exhibit deficits in social cognition that play a large role in functional impairments and are associated with altered activity in underlying functional networks. Targeted computerized cognitive training on abilities that support social cognition, such as emotion recognition, have been shown to improve behavioral performance. However, it is unclear how this training impacts the underlying neural networks. This study assesses changes in social cognitive functional networks following targeted cognitive training in individuals with schizophrenia.