Mechanisms Underlying Motivational Dysfunction in Schizophrenia

Abstract

Negative symptoms are a debilitating feature of schizophrenia which are often resistant to pharmacological intervention. The mechanisms underlying them remain poorly understood, and diagnostic methods rely on phenotyping through validated questionnaires. Deeper endo-phenotyping is likely to be necessary in order to improve current understanding. In the last decade, valuable behavioural insights have been gained through the use of effort-based decision making (EBDM) tasks. These have highlighted impairments in reward-related processing in schizophrenia, particularly associated with negative symptom severity. Neuroimaging investigations have related these changes to dysfunction within specific brain networks including the ventral striatum (VS) and frontal brain regions. Here, we review the behavioural and neural evidence associated with negative symptoms, shedding light on potential underlying mechanisms and future therapeutic possibilities. Findings in the literature suggest that schizophrenia is characterised by impaired reward based learning and action selection, despite preserved hedonic responses. Associations between amotivation and reward-processing deficits have not always been clear, and may be mediated by factors including cognitive dysfunction or dysfunctional or self-defeatist beliefs. Successful endo-phenotyping of negative symptoms as a function of objective behavioural and neural measurements is crucial in advancing our understanding of this complex syndrome. Additionally, transdiagnostic research–leveraging findings from other brain disorders, including neurological ones–can shed valuable light on the possible common origins of motivation disorders across diseases and has important implications for future treatment development.

Effort-Cost Decision-making Among Individuals With Schizophrenia

“…The computational origin of this deficit may be related to recent evidence showing that dependencies exist between effort computation and reward information such that large monetary prospects increased cost estimates for healthy participants. 49 Clarifying this issue will thus require better descriptions of the interactions between reward information, cognitive impairments, 50 and effort allocation 51 in individuals with schizophrenia. At the neural level, it is likely that lower effort-cost decision-making performance is associated with frontostriatal dysfunction in patients with schizophrenia.…”

“…A possible explanation is that several studies included in the meta-analyses relied on questionnaires containing clinical manifestations that are no longer regarded as part of the consensus statement definition of the negative syndrome of schizophrenia. 56 Hence, it was recently suggested that abstract thinking and attention impairments included in the PANSS and the SANS questionnaires could be more related to general cognitive impairment, 51 which is thought to develop independently of negative symptom pathways in schizophrenia. 57 Moreover, total scores of all negative symptom scales typically include assessments of nonmotivational negative symptoms (eg, inability to show emotion, reduction in quantity of words spoken), which are less directly related to effort-cost computations.…”

Reexamination of the relationships among neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning in chronic schizophrenia

“…Few studies have investigated the relationships between neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning. (Saleh et al, 2021) argued that self-defeatist beliefs mediated the relationship between motivational and reward processing de cits and negative symptoms, particularly apathy and avolition, rather than that between alogia and blunted affect. A randomized clinical trial identi ed self-defeatist beliefs to play a mediating role in the relationship between experiential negative symptoms and social functioning (Granholm et al, 2018).…”

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

“…Tasks that probe people’s willingness to expend effort for reward, often inspired by pre-clinical studies, investigate the behavioural mechanisms of motivational deficits by probing the different phases of decision making [ 18 ]. One example is the process of option selection, where participants are asked to weigh up the benefits (e.g., potential reward) and costs (e.g., effort required to obtain that reward) of a decision prior to initiating goal-directed action [ 18 , 20 , 21 ]. A commonly used option selection paradigm in Schizophrenia is the ‘Effort Expenditure for Rewards Task’ (EEfRT) [ 22 – 25 ], where people are asked to choose between a low reward–low effort option or a high reward–high effort one [ 22 ].…”