Avolition as the core negative symptom in schizophrenia: relevance to pharmacological treatment development

Abstract

Negative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed.

How do we address treating the negative symptoms of schizophrenia pharmacologically?

“…The five core negative symptoms include avolition (decreased motivation), anhedonia (decreased experience/anticipation of pleasure), asociality (decreased interest/ opportunity in social interactions), blunted affect (decreased emotional expression) and alogia (decreased speech production) [2]. Factor models have further narrowed negative symptoms to two main factors: decreased expression and decreased motivation and pleasure [3]. Functional disability in schizophrenia is highly correlated with negative symptoms [3].…”

“…Factor models have further narrowed negative symptoms to two main factors: decreased expression and decreased motivation and pleasure [3]. Functional disability in schizophrenia is highly correlated with negative symptoms [3]. The present report focuses on the treatment landscape of negative symptoms in schizophrenia, including both Federal Drug Authority (FDA) or other regulatory bodies approved and investigational treatments.…”

Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia

“…Because aspects of negative symptoms manifest in 19 distinct DSM-5 categories 41 and in adolescents suspected of prodromal and spectrum schizophrenia, 42 future trials targeting negative symptoms or aspects of negative symptoms such as avolition 43 across DSM categories or along the research domain criteria principles 44 will be conducted.…”

Mechanisms Underlying Motivational Dysfunction in Schizophrenia

“…Motivation deficits appear to be central to the negative syndrome (Strauss et al, 2019c(Strauss et al, , 2021). An emerging framework that has been used to conceptualize the motivational aspects of negative symptoms is that of effort-based decision making for rewards (EBDM).…”