Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
BackgroundAbnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).MethodCognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.ResultsPatients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.ConclusionThis study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Background Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains. Methods Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included. Results Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22–7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36–3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16–4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15–0.85)]. None of the moderators included significantly change the results. Conclusions These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.
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