Disorder at the Synapse: How the Active Inference Framework Unifies Competing Perspectives on Depression

Depression is one of the most disabling of all disorders across the community, yet many aspects of the disorder remain contentious. Psychosocial and biological perspectives are often placed in opposition to one another, which in part reflects a failure of our explanatory frameworks. The active inference account of brain function breaks down this dualism, demonstrating that bodily processes are deeply integrated with the social world. It shows us that there is no contradiction in understanding depression as a product of the social environment at the same time as having a brain basis and manifesting in biological symptoms. From an active inference perspective, depression can be thought of as a synaptopathy: a disorder that arises from alterations to the excitatory-inhibitory balance enacted at the synapse, reflecting the interoceptive precision-weightings that have changed in the context of psychosocial instability. Therapies that alleviate depressive symptoms act at different levels of the active inference framework to re-weight precision estimates and the confidence we have in our predictions: this is true for psychotherapies, lifestyle interventions and antidepressant medications. Their effectiveness is often only partial, and while different treatment modalities can complement one another, there is a need for continued development of new and better treatment options.