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

Area of Science:

• Neuroscience
• Psychiatry
• Computational Psychiatry

Background:

• Depression is a highly disabling global disorder with contentious aspects.
• Psychosocial and biological views of depression are often contrasted, highlighting limitations in current explanatory models.
• Active inference offers a unified framework integrating bodily and social processes.

Purpose of the Study:

• To present an active inference account of depression, bridging psychosocial and biological perspectives.
• To conceptualize depression as a synaptopathy resulting from altered synaptic function.
• To explain how various depression therapies interact with the active inference framework.

Main Methods:

• Utilizing the active inference framework to model brain function and its relation to depression.
• Describing depression as a synaptopathy involving excitatory-inhibitory balance and interoceptive precision.
• Analyzing how different therapeutic interventions (psychotherapy, lifestyle, medication) modulate precision estimates within the active inference model.

Main Results:

• Active inference resolves the dualism between psychosocial and biological explanations of depression.
• Depression is framed as a synaptopathy arising from altered interoceptive precision due to psychosocial instability.
• Therapies for depression function by adjusting precision estimates and prediction confidence at various levels of the active inference framework.

Conclusions:

• Depression can be understood as a disorder with both social and biological underpinnings, integrated via active inference.
• Synaptic alterations and interoceptive precision are key mechanisms in the active inference model of depression.
• Current therapies partially alleviate symptoms by modifying precision weightings, underscoring the need for improved treatment development.