Revealing the impact of psychiatric comorbidities on treatment outcome in early psychosis using counterfactual model explanation

Introduction: Psychiatric comorbidities have a significant impact on the course of illness in patients with schizophrenia spectrum disorders. To accurately predict outcomes for individual patients using computerized prognostic models, it is essential to consider these comorbidities and their influence. Methods: In our study, we utilized a multi-modal deep learning architecture to forecast symptomatic remission, focusing on a multicenter sample of patients with first-episode psychosis from the OPTiMiSE study. Additionally, we introduced a counterfactual model explanation technique to examine how scores on the Mini International Neuropsychiatric Interview (MINI) affected the likelihood of remission, both at the group level and for individual patients. Results: Our findings at the group level revealed that most comorbidities had a negative association with remission. Among them, current and recurrent depressive disorders consistently exerted the greatest negative impact on the probability of remission across patients. However, we made an interesting observation: current suicidality within the past month and substance abuse within the past 12 months were associated with an increased chance of remission in patients. We found a high degree of variability among patients at the individual level. Through hierarchical clustering analysis, we identified two subgroups: one in which comorbidities had a relatively limited effect on remission (approximately 45% of patients), and another in which comorbidities more strongly influenced remission. By incorporating comorbidities into individualized prognostic prediction models, we determined which specific comorbidities had the greatest impact on remission at both the group level and for individual patients. Discussion: These results highlight the importance of identifying and including relevant comorbidities in prediction models, providing valuable insights for improving the treatment and prognosis of patients with psychotic disorders. Furthermore, they open avenues for further research into the efficacy of treating these comorbidities to enhance overall patient outcomes.