Synaptic Mechanisms Regulating Mood State Transitions in Depression.

Publication Type	Review
Authors	Parekh P, Johnson S, Liston C
Journal	Annu Rev Neurosci
Volume	45
Pagination	581-601
Date Published	05/04/2022
ISSN	1545-4126
Keywords	Antidepressive Agents, Depression
Abstract	Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.
DOI	10.1146/annurev-neuro-110920-040422
PubMed ID	35508195
PubMed Central ID	PMC11577286