Psychiatric disorders have been a growing global public health crisis. One in ten Americans reported experiencing depressive symptoms during the COVID-19 pandemic. Alarmingly, the suicide rate in the United States has increased by approximately 35% over the past two decades. Despite the unfortunate prevalence of these conditions, current treatment options remain limited in reliability. Between 30-55% of individuals receiving antidepressant treatment experience treatment-resistant depression, leading to a critical need for more effective and targeted approaches. These must come from a deeper understanding of the underlying genetic mechanisms that contribute to symptom expression.
Past studies have shown how the dysfunction of interneurons (INs), which control the neural network activity in the brain, leads to an imbalance in neural circuits, playing a key role in psychiatric disorders. Because of this, large-scale genome wide association studies have begun to identify specific IN genes that may be involved in psychiatric disorder susceptibility. Among these, Traf3 has stood out as a gene with likely risk for major depressive disorder (MDD), suicide, and PTSD, though its biological basis remains unknown.
The Bygrave Lab at the Tufts Medical School has been researching this protein to get some answers, and I’m excited to join the team. Over the summer, I will be conducting a series of behavioral tests on a group of mice with the Traf3 protein deleted specifically from their interneurons, Traf3 knockout mice. Some of these tests are the open field test, the elevated plus maze, and cued fear conditioning. Each of these will help me measure the rodents’ locomotor activity, their drive to explore a “safe” enclosed arm compared to a more “dangerous” anxiogenic open arm, and their fear of learning, respectively. At the end of the summer, these findings will further explain the role Traf3 plays in interneurons.
As mentioned previously, despite psychiatric disorders’ increasing effects on hundreds of millions of people worldwide, treatments remain inconsistent. This is why I believe there is an urgent need for research that uncovers the biological mechanisms underlying these disorders. By investigating the role of Traf3 in inhibitory interneurons, I hope to help more deeply understand how genetic risk factors contribute to psychiatric pathology. While this is one step in the process of obtaining more accurate treatments, I’m confident it will contribute to the growing efforts to ultimately improve individuals’ lives affected by psychiatric disorders.