Cognitive flexibility and depression remission: A narrative review

In depression, cognitive flexibility - the ability to adjust cognitive strategies in response to a changing environment in order to adapt one's behavior appropriately - is frequently impaired. This impairment is thought to contribute to difficulties in modifying maladaptive cognitive patterns and may influence responsiveness to antidepressant treatments. Treatment resistance remains a major clinical challenge, with approximately half of patients failing to respond to first-line antidepressant therapies. Moreover, residual symptoms characterized by rigid and maladaptive cognitive schemas are common in treatment-resistant depression and may prevent full remission. In this context, understanding the role of cognitive flexibility in the recovery process appears particularly relevant.

This narrative literature review aimed to explore the link between depression, cognitive flexibility, and their implications for remission, through the lens of cognitive neuroscience. The following keywords were used to search Pubmed: "depression", "cognitive flexibility", "cognitive functions", "homeostasis" and "allostasis".

First, we conceptualized the pathophysiology of depression as a homeostatic imbalance, i.e. the disruption of allostatic mechanisms leading to homeostasis and functional remission both at the cognitive and neural level. On the neural level, there is an imbalance in the coordination of the salience network (SN), the central executive network (CEN) and the default mode network (DMN), characterized by altered functional connectivity between those networks. The DMN is hyperactivated, and the SN is disconnected, hindering the activation of the CEN. Allostatic mechanisms cannot be implemented, hindering return to homeostasis, i.e. depression remission. A more balanced functional connectivity between these networks would promote the deployment of cognitive flexibility which would contribute to the mobilization of allostatic cognitive resources such as attentional control and adaptive situation (re-) appraisal, both essential to the remission process.