Negative symptoms and amotivation in early psychosis : relationships with clinical variables, neurocognition and functional outcome

Abstract

Negative symptoms are a core psychopathological dimension of schizophrenia and related psychoses, and are associated with pronounced functional impairment and limited response to available treatments. Emerging evidence indicates that negative symptoms are prevalent in the initial course of psychotic illness and may represent an important therapeutic target for early functional recovery. However, previous research mainly focused on chronically-ill patients, while negative symptoms in early psychosis are understudied. This thesis aimed to systematically investigate various important aspects of negative symptoms in first-episode psychosis (FEP) and at-risk mental state (ARMS) samples in Hong Kong through a series of our studies published between 2013 and 2019. First, we assessed the impact of premorbid adjustment and duration of untreated psychosis on negative symptom outcome in FEP. Second, we examined the prevalence and correlates of primary negative symptoms in FEP. We then applied individual-based trajectory analysis to identify distinct early-stage negative symptom course patterns in FEP cohort, as well as to investigate baseline predictors of symptom trajectories and the effect of persistent-negative-symptom trajectory on long-term functional and clinical outcomes. Third, we evaluated the relationship of motivational impairment (amotivation), a core negative symptom subdomain, with functional outcome in FEP. Additionally, two complementary statistical approaches, namely theory-driven structural equation modeling and data-driven network analysis, were employed to clarify complex interrelationships between amotivation, psychosocial functioning, cognitive deficits, and other clinical dimensions. Fourth, we studied negative symptoms in ARMS by verifying the twofactor symptom structure and the differential relationships of symptom subdomains (amotivation and diminished expression) with psychosocial functioning. Lastly, we attempted to identify specific neurocognitive mechanisms that may contribute to amotivation in FEP. We first examined whether individual executive function subcomponents, classified on the basis of fractionated approach, selectively predicted amotivation in FEP patients. Then, we adopted translational experimental paradigms on reward-processing encompassing reinforcement learning (RL) and effort-based decision-making (EBDM) to investigate whether impairments in these neurocognitive domains were specifically associated with levels of amotivation in FEP. Overall, our studies affirm a crucial role of negative symptoms, especially amotivation, in determining functional outcome in FEP and ARMS samples. Importantly, early-stage persistent-negative-symptom trajectory significantly predicted poor long-term functional and clinical outcomes, thereby underscoring negative symptoms emerged in the initial years of treatment as a critical treatment target in early intervention for psychosis to prevent clinical deterioration and enduring functional disability. Our results on RL and EBDM impairments and their significant associations with amotivation provide more nuanced understanding about the potential neurobiological abnormalities underlying motivational deficits in first-episode populations. Important clinical implications of our study findings as well as future directions of negative symptom research were also discussed in the thesis.