ALE meta-analysis of cognitive control, motivation, and effort in schizophrenia and mood disorders: Implications for multidimensional apathy

Abstract

Background: Apathy is present in about 50% of patients suffering from schizophrenia (SZ) and mood disorders (MD). Even though these two disorders are different, in psychiatry, apathy refers typically to the same unidimensional clinical entity, sharing the same pathophysiological processes and symptoms regardless of the underlying diagnosis. Neurology proposes another perspective: three forms of apathy —emotional, executive, and initiative— are related to a disturbance in motivation, cognitive control, and effort-based decision-making, respectively. We explored whether this latter model can be applied in psychiatry by identifying differences between SZ and MD through a PRISMA meta-analysis of imaging studies on reward processing, cognitive control, and effort-based decision-making networks. Methods: We searched the Sleuth BrainMap and PubMed databases for studies on SZ, MD, and/or healthy controls using tasks probing reward processing, cognitive control, and effort-based decision-making. Twenty-three functional MRI studies were identified and included for a coordinate-based activation likelihood estimation analysis. Results: In SZ, hypoactivity in reward-processing structures, a specific hyperactivity in the right cerebellar vermis that has previously been linked to emotional blunting and apathy, and a lack of activation during effort-based decision-making that could imply an impaired reward processing, suggest a dominant form of emotional apathy. In MD, hypoactivity in both cognitive control and reward-processing structures, which has previously been linked to the co-occurrence of executive difficulty and amotivation, suggests a mixed emotional/executive apathy profile. Limitations: The main limitations include the use of two databases, a small number of existing studies, a lack of control over treatment, age, and disorder severity, as well as the inherent heterogeneity of each diagnosis. Conclusion: By highlighting different dominant forms of apathy in SZ and MD, these results could help target new individualized treatment strategies in precision psychiatry based on a multidimensional conceptualization of apathy. Registration: This review was not prospectively registered.