New Brain Mechanism Discovered for PTSD Treatment: Implications and Insights

In a groundbreaking study conducted by researchers at the Institute for Basic Science (IBS) and Ewha Womans University, a novel brain mechanism contributing to post-traumatic stress disorder (PTSD) has been uncovered, along with a promising drug candidate that may alleviate its symptoms. The findings, published on July 29, 2025, reveal that excessive gamma-aminobutyric acid (GABA) production by astrocytes in the brain disrupts the ability to extinguish fear memories, a common challenge faced by PTSD patients. This research sheds light on the underlying neurobiological mechanisms of PTSD and offers hope for improved therapeutic strategies.

The lead authors, Dr. C. Justin Lee of IBS and Professor In Kyoon Lyoo from Ewha Womans University, highlighted that current treatments for PTSD primarily target serotonin receptors, which often provide limited relief. The study, which involved brain imaging of over 380 participants, found that PTSD patients exhibited elevated GABA levels and decreased blood flow in the medial prefrontal cortex (mPFC), a region crucial for fear regulation. This impaired neural activity was linked to the persistent nature of traumatic memories in individuals suffering from PTSD.

To investigate the origins of excess GABA, the researchers utilized postmortem human brain tissue and PTSD-like mouse models. They identified astrocytes—supportive cells in the brain—as the source of abnormal GABA production, specifically through the enzyme monoamine oxidase B (MAOB). The research team discovered that inhibiting MAOB with a drug named KDS2010, which selectively blocks this enzyme, reversed PTSD-like symptoms in mice. KDS2010 has successfully completed Phase 1 safety trials in humans, positioning it as a potential candidate for treating PTSD.

Dr. Woojin Won, a co-first author of the study and postdoctoral researcher at IBS, stated, "Our findings not only uncover a novel astrocyte-based mechanism underlying PTSD but also provide preclinical evidence for a new therapeutic approach using an MAOB inhibitor." This innovative approach emphasizes a shift in focus from neuronal activity to astrocytic contributions in the pathophysiology of PTSD.

The study applied a reverse translational strategy, starting with clinical observations and moving backward to identify cellular dysfunctions. This methodology successfully linked clinical findings to laboratory results, providing a robust framework for future research. Dr. Lee underscored the significance of this approach, stating, "By identifying astrocytic GABA as a pathological driver in PTSD and targeting it via MAOB inhibition, we open a completely new therapeutic paradigm not only for PTSD but also for other neuropsychiatric disorders such as panic disorder and depression."

The implications of this research extend beyond PTSD, with the potential for astrocyte-targeted therapies addressing a range of neuropsychiatric conditions. As KDS2010 advances into Phase 2 clinical trials, it represents a promising step toward offering new treatment options for patients who have not responded adequately to traditional therapies.

The study, titled "Astrocytic gamma-aminobutyric acid dysregulation as a therapeutic target for posttraumatic stress disorder," was published in the *Signal Transduction and Targeted Therapy* journal (Yoon, S., et al., 2025). This research marks a significant milestone in understanding PTSD and highlights the critical role of glial cells in psychiatric disorders, paving the way for innovative treatment strategies aimed at improving patients' quality of life.