INSIGHTS Krishna Vadodaria Uncovering the mysteries of depression
At some point in their life, one in six people in the United States will experience depression, according to the American Psychiatric Association. Major depressive disorder is one of the most prevalent psychiatric conditions, and a substantial public health problem. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for depression, yet they are ineffective in almost one-third of patients. Staff Scientist Krishna Vadodaria wants to know why.
Vadodaria is using novel laboratory techniques to search inside human neurons to discover the biological basis for psychiatric disorders and why some depressed patients do not respond to SSRIs. “As a staff scientist, I am able to stay focused on the science, and I have the freedom to pursue project ideas that interest me most,” Vadodaria says. She hopes her research will eventually lead to improved treatment strategies and better outcomes for patients with depression and other psychiatric disorders.
As a staff scientist in the Gage lab, Vadodaria contributes to new ways of studying psychiatric disorders by using patient-derived neural cells. She uses stem-cell reprogramming techniques to turn patient skin-cell samples into induced pluripotent stem cells (iPSCs) and then into neurons. This relatively new technology, called iPSC-based neural modeling, allows Vadodaria to directly observe the neural differences between depressed patients that respond to SSRIs and those who do not.
Specifically, Vadodaria examines how SSRIs increase the levels of the neurotransmitter serotonin at synapses (the locations where neurons communicate) and how patient neurons respond. Recently, she found that the neurons of patients with SSRI-resistant depression are shaped differently than the neurons of patients who respond to SSRIs and are more active in response to serotonin. Thus, the neurons of patients with SSRI-resistant depression may be making inappropriate connections with other neurons and may have a different response pattern than they are supposed to have. Vadodaria’s results have led to two first-author publications this year, both in the journal Molecular Psychiatry. The findings also have implications for other psychiatric conditions that involve abnormalities in the serotonergic system, such as bipolar disorder and schizophrenia.
Vadodaria recently welcomed her first child, a baby boy named Arjun. “Having a child has been a humbling learning experience, as I am witnessing firsthand how biological states can affect mental states,” says Vadodaria. “Experiencing the sheer power of biology reaffirms my desire to continue studying the neurobiology of psychiatric conditions.”
Today, Vadodaria’s parents live in India, but they visit San Diego. “I have been blessed to have parents that have selflessly encouraged me to pursue my interests and strive for excellence. They never discourage me from taking the harder route, even when that means living halfway around the world from them,” she says.
Vadodaria holds a second-degree black belt in a style of karate called Shōtōkan. For years, she taught students of all ages the strong basic stances (kihon), the patterns of powerful movements (kata) and the dynamic sparring techniques (kumite). The self-discipline she learned from Shōtōkan has become a part of her life, and she credits this skill with helping her to be a determined and diligent scientist today.
Path to Salk
Vadodaria is originally from India but spent her teenage years near the city of Winston-Salem, in northwestern North Carolina; her father was an IT consultant whose job brought the family to the United States for his longer projects. After living in North Carolina, her family returned to India. She earned a bachelor’s degree at the University of Mumbai, where a supportive professor in the microbiology department inspired her to study biology through experimental science.
Vadodaria’s passion for discovery only grew from there. While earning her master’s degree at the Tata Institute of Fundamental Research, in Mumbai, she was exposed to the captivating world of the neurobiology of mood and behavior. She examined early-life stressors in animal models of depression, and looked at how maternal separation affected the neural pathways related to the stress response later in life. After completing her master’s degree, she pursued her PhD at the Swiss Federal Institute of Technology in Zurich, studying adult neurogenesis, a form of neural plasticity thought to be dysregulated in depressive disorders.
Once she graduated, Vadodaria sought postdoctoral fellowships where she could continue to study the neurological basis of psychiatric disorders. Having lived on three continents, she believed that the United States offered a great chance to conduct cutting-edge research. “I was elated to have an opportunity to do my postdoctoral training at the Salk Institute, where I could continue to grow as a scientist under the guidance of such a renowned and respected neuroscientist as Professor Gage.”
“I am inspired to continue working in this field because I believe that new discoveries and knowledge gained from experimental research can make an impact on how we understand and treat psychiatric disorders,” says Vadodaria. “Psychiatric disorders, such as depression, pose an interesting research challenge because they are diverse in their symptomology, not easy to model using animals, and stem from multiple genes. The long-term goal of my research is to use patient-derived neural cells to better characterize the cellular neurobiology of psychiatric diseases. Science is my happy place, and I hope I can make a positive impact through my research.”
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- Krishna Vadodaria – Uncovering the mysteries of depressionStaff Scientist Krishna Vadodaria's research on human neurons is helping to uncover the biological basis for psychiatric disorders and why some depressed patients do not respond to SSRIs.