Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia

Abstract

Background: Motivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia. Methods: Forty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed. Results: Overall, TRS patients were significantly less motivated than controls during effort-based decision making. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter. Conclusion: Motivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

Investigating disorder-specific and transdiagnostic alterations in model-based and model-free decision-making

“…Interestingly, it seems that the schizophrenia patients in our sample were particularly insensitive to the outcome of their choices, causing a disruption of model-free decision-making strategies. The insensitivity to reward has been shown across all stages of schizophrenia and has been associated with negative symptoms, especially anhedonia, and cognitive deficits 55,61,103,104 . Thus, our findings are in line with previous literature elucidating that these patients generally possess an impairment in reward anticipation and effort-based decision-making 8,61 .…”