Year: 2022
Type: review
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.
Source: Annual Review of Neuroscience
Authors: Puja K. Parekh, Shane B. Johnson, Conor Liston
Institution: Weill Cornell Medicine
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Development of opioid and ketamine probes for in vivo photopharmacology, Corticostriatal and Corticoinsular Circuit Mechanisms Underlying Stress Effects on Effort-based Reward Processing, Impact of BDNF on the Development of Social Behavior Circuits, Prefrontal Cortical Microcircuit Mechanisms of Working Memory Deficits in Chronic Stress, Neuromodulatory control of prefrontal circuit function and reward-seeking
OpenAlex ID: W4229007163