From memory disorders to the development of depression: A system approach

In this review, a hypothesis explaining the origin and genesis of depression development from the perspective of a holistic functional system of behavioral control is proposed. The core of the functional system is the memory apparatus, on which all other key components of the behavioral control system (sensory information, motivation, reinforcement, and motor activity) are interlocked. In the organization of memory traces (engrams) there are two inputs, sensory and motivational, through which the stimulus-stimulus (S-S) and stimulus-motor (S-R) engrams are formed. These engrams are organized and actualized by means of forward and backward conditional connections between cortical representations of sensory information and motivational structures of the brain. Through feedback connections from reinforcing (emotional) input to the memory apparatus, the S-S and S-R engrams are consolidated or weakened depending on the strength of reward or negative events. Depression begins with a breakdown in memory mechanisms. These breakdowns are related to problems with the three mentioned memory inputs: sensory, motivational, and reinforcing (emotional). Disruptions in sensory and motivational input lead to an inability to form new memory engrams, their actualization and retrieval. This creates difficulty in solving current and past unresolved problems, eliciting more accumulation and increasing difficulties in their solving. Unresolved tasks lead to weakening of the reinforcing input, and further impairment of consolidation of the acting engrams. Another reason for the weakening of reinforcing input is excessive action of directly harmful events or constant chronic stress. The review presents the current literature and some data from our laboratory in favor of each memory input's contribution and their impact on the development of depression, when they are problematic.