Abstracts
3427214
(#48) Beyond Monoamines: Rethinking MDD Treatments Through AMPA Receptor Modulation
Abstract: Despite the availability of numerous pharmacologic treatments for major depressive disorder (MDD), many patients fail to achieve remission with these medications. Persistent symptoms such as low mood, anhedonia, reduced motivation, cognitive difficulties, and impaired daily functioning often remain even after multiple treatment attempts. Delayed onset of clinical benefit, incomplete symptom resolution, and safety and tolerability challenges further complicate treatment optimization in MDD, underscoring the need for pharmacologic approaches that move beyond currently available mechanisms.
Increasing evidence suggests that MDD may involve disruptions in how brain cells communicate and adapt (i.e., impaired neuroplasticity), rather than being solely due to imbalances in serotonin or other monoamines. Glutamate is the brain's primary excitatory signaling chemical and plays a critical role in neuroplasticity. In MDD, researchers hypothesize that glutamate signaling may become less efficient, leading to weaker connections between brain cells and reduced flexibility in key mood-regulating circuits.
AMPA receptors are important components of glutamate signaling that help strengthen communication between neurons. Alterations in AMPA receptor function and expression have also been demonstrated with MDD, potentially contributing to reduced synaptic strength and impaired neural communication. Preclinical and translational research suggests that enhancing AMPA receptor activity may improve how brain cells communicate and activate neuronal pathways associated with recovery and resilience.
Together, these findings support AMPA receptor modulation as a promising mechanism that could address inadequate response and unmet needs in MDD by targeting signaling pathways in brain communication that are beyond current monoaminergic approaches.
Short Description: Major depressive disorder (MDD) is associated with significant disease burden and unmet needs due to delayed and/or inadequate treatment response and safety/tolerability challenges with current pharmacologic treatments. Emerging evidence suggests disruptions in glutamate signaling and AMPA receptor function may contribute to impaired signaling between neurons underlying depressive symptoms. This presentation reviews the rationale for targeting AMPA receptors as a novel therapeutic approach aimed at improving neuroplasticity and addressing the limitations of traditional monoamine-based treatments.
Name of Sponsoring Organization(s): Neurocrine Biosciences, Inc.
Increasing evidence suggests that MDD may involve disruptions in how brain cells communicate and adapt (i.e., impaired neuroplasticity), rather than being solely due to imbalances in serotonin or other monoamines. Glutamate is the brain's primary excitatory signaling chemical and plays a critical role in neuroplasticity. In MDD, researchers hypothesize that glutamate signaling may become less efficient, leading to weaker connections between brain cells and reduced flexibility in key mood-regulating circuits.
AMPA receptors are important components of glutamate signaling that help strengthen communication between neurons. Alterations in AMPA receptor function and expression have also been demonstrated with MDD, potentially contributing to reduced synaptic strength and impaired neural communication. Preclinical and translational research suggests that enhancing AMPA receptor activity may improve how brain cells communicate and activate neuronal pathways associated with recovery and resilience.
Together, these findings support AMPA receptor modulation as a promising mechanism that could address inadequate response and unmet needs in MDD by targeting signaling pathways in brain communication that are beyond current monoaminergic approaches.
Short Description: Major depressive disorder (MDD) is associated with significant disease burden and unmet needs due to delayed and/or inadequate treatment response and safety/tolerability challenges with current pharmacologic treatments. Emerging evidence suggests disruptions in glutamate signaling and AMPA receptor function may contribute to impaired signaling between neurons underlying depressive symptoms. This presentation reviews the rationale for targeting AMPA receptors as a novel therapeutic approach aimed at improving neuroplasticity and addressing the limitations of traditional monoamine-based treatments.
Name of Sponsoring Organization(s): Neurocrine Biosciences, Inc.
