Social cognition in schizophrenia: associations with clozapine use across theory of mind and emotion recognition

Background

Clozapine is widely regarded as the gold standard treatment for treatment-resistant schizophrenia; however, its effects on social cognition remain insufficiently understood. Social cognition encompasses multiple domains, including theory of mind and emotion recognition, both of which are closely associated with functional outcomes and everyday social functioning. Impairments in these domains contribute significantly to disability in schizophrenia. Although cognitive deficits are well documented, it remains unclear whether clozapine has a specific influence on social cognitive processes beyond its effects on symptom severity. Clarifying this relationship may have important implications for treatment selection and functional recovery. This study aimed to compare social cognitive performance, clinical characteristics, and sociodemographic variables between patients receiving clozapine and those treated with other antipsychotic medications.

Methods

This cross-sectional study included patients diagnosed with schizophrenia. Participants were divided into those receiving clozapine (n=20) and those receiving other antipsychotic treatments (n=23). Sociodemographic variables (age, sex, education level, and employment status) and clinical characteristics (age at onset, illness duration, history of suicide, and history of violence) were recorded. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scales (CGI-Severity, CGI-Improvement, CGI-Efficacy Index). Ethical approval was obtained from the local institutional review board, and written informed consent was obtained from all participants.

Social cognition was assessed across specific domains. Theory of mind was evaluated using the Hinting Task, while emotion recognition was assessed using the Facial Emotion Recognition Test and Facial Emotion Discrimination Test. All variables were analyzed as continuous measures without predefined cut-off values to preserve variability and statistical power.

Normality of distribution was assessed using the Shapiro–Wilk test. Independent samples t-tests were used for normally distributed variables, and Mann–Whitney U tests were applied when appropriate. Categorical variables were compared using chi-square tests. A two-tailed p-value of less than 0.05 was considered statistically significant.

Results

No significant differences were observed between groups in terms of sociodemographic variables, including age, sex distribution, education level, and employment status (all p>0.05). Similarly, clinical variables such as age at onset, illness duration, and history of suicide or violence did not differ significantly between groups (all p>0.05). Clinical severity measures were also comparable, including PANSS positive (p=0.13), PANSS negative (p=0.98), PANSS general psychopathology (p=0.40), and CGI scores (all p>0.05).

In contrast, significant differences were found in social cognition. Patients receiving clozapine demonstrated better performance in theory of mind, as measured by the Hinting Task (15.65±2.94 vs 13.57±3.36; p=0.036). They also performed significantly better in emotion recognition tasks, including the Facial Emotion Recognition Test (12.25±1.92 vs 9.96±2.58; p=0.0019) and the Facial Emotion Discrimination Test (23.95±3.28 vs 21.17±3.81; p=0.014).

Conclusions

Despite comparable clinical severity and sociodemographic characteristics, patients treated with clozapine showed better performance in both theory of mind and emotion recognition domains. These findings suggest a domain-specific association between clozapine use and social cognitive functioning. However, due to the cross-sectional design, causal interpretations remain limited. Further studies with larger samples and longitudinal designs are needed to clarify the direction and underlying mechanisms of this relationship.

References

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