Pathophysiology of negative symptom dimensions of schizophrenia – Current developments and implications for treatment

Negative symptoms of schizophrenia comprise a group of severe symptoms contributing to high disease burden and poor long-term prognosis. Conceptual work has shown that these symptoms can be mapped onto, at least, two distinct dimensions: apathy including the domains avolition, asociality and anhedonia, and diminished expression including the domains blunted affect and alogia. Growing evidence suggest that these dimensions have partly distinct behavioral, cognitive and neural correlates. Nonetheless, modulation and treatment of specific processes and brain correlates related to these negative symptom dimensions through behavioral, pharmacological, and brain stimulation interventions remains poorly understood. Here, we address this question by employing an integrative approach and comprehensively synthesizing the current literature on neuroimaging, behavior and clinical studies of both negative symptom dimensions. While considerable progress has been made, it remains an open challenge to develop integrative mechanistic pathophysiological models for apathy and diminished expression. We conclude that such multi-level frameworks are key for the development of new biological and psychosocial treatments and may advance progress towards an individualized treatment of negative symptoms.