2025/03/11 by Robin Nusslock, Vijay A. Mittal, Lauren B. Alloy · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Schizophrenia research and treatment #Bipolar Disorder and Treatment #Receptor Mechanisms and Signaling
paper · doi:10.1146/annurev-clinpsy-080822-041621
openalex publication_date 2025/03/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Major depressive disorder (MDD), bipolar disorder, and schizophrenia involve disruptions in processing rewarding stimuli. In this review, we propose that distinct mechanistic pathways underlie these disruptions in mood disorders versus schizophrenia, and we highlight the importance of understanding these differences for developing personalized treatments. We summarize evidence suggesting that reward processing abnormalities in mood disorders are driven by dysregulated motivational systems; MDD is characterized by blunted responses to reward cues, and bipolar disorder is characterized by heightened responses. In contrast, we argue that reward processing disruptions in schizophrenia do not reflect abnormalities in motivation or hedonic experience; rather, they reflect impairments in the cognitive representation of past and future rewards as well as misdirected attention to irrelevant stimuli. To integrate these findings, we present a neurodevelopmental framework for the onset of mood and psychotic disorders and explore how disruptions in normative brain development contribute to their pathophysiology, timing, and onset. Additionally, we move beyond viewing these conditions as homogeneous disorders and discuss how reward processing profiles may align with specific symptom dimensions.