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Transforming the understanding
and treatment of mental illnesses.

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Alaina Tillman, Winner of the 2023 NIMH Three-Minutes Talks Competition

Transcript

Hi, my name is Alaina Tillman. I'm excited to present my talk to you today. 

Psychiatry is moving toward a precision medicine model. For patients diagnosed with depression, selective serotonin re-uptake inhibitors, SSRIs, are the most common treatment administered. However, for SSRIs, only about half of patients experience a relief of symptoms. 

For patients that have tried at least two treatments that haven't worked to relieve symptoms, a subpopulation has been classified as treatment-resistant depression. It isn't surprising that there's differences in treatment outcomes as the brain is incredibly complex, connected to multiple body systems, and interacting within a dynamic environment. 

The classification of the subpopulation and the described complexity highlights that a different approach needs to be considered. The bio-psychosocial approach can evaluate all the different aspects in one's life and how they are connected, specifically with the immune system, to describe these differences in treatment outcomes. There's a bidirectional interaction between the central nervous system and the immune system.

This is highlighted through the comorbidity between depression and autoimmune conditions. Studies show that histamine, a biological mark of immune activation, as well as social stress that also activates the immune system, attenuates the antidepressant response of SSRIs. 

One treatment that my lab has been exploring for treatment-resistant depression patients is ketamine. Ketamine mainly acts by blocking NMDA receptors, but other mechanisms of action have been described. Many treatment-resistant depression patients in my lab experience a relief of symptoms after intravenous ketamine administration. 

I'm interested in understanding the different aspects that influence these patients to respond to ketamine despite not responding to conventional treatments like SSRIs within the context of the immune system. One question that I'm interested in exploring is whether these treatment-resistant depression patients have a dysregulated immune response, such as from a biological autoimmune condition or stress. If so, does ketamine act on a different pathway to override this dysregulated immune response that once impacted other treatments to then cause a reduction in depressive symptoms? 

Another question that I'm interested in exploring is whether there's any pro-inflammatory and anti-inflammatory immune biomarker differences between ketamine responders and non-responders. Within my lab, there are dozens of serum samples collected from treatment-resistant depression, patients that have received ketamine. 

To explore these questions, I can run multiplex immunoassays using these samples, pre- and post-ketamine to look at differences in immune biomarkers. Overall, studies show that biological and social immune activation can predispose someone to depression, but we're now beginning to understand that it can also impact treatment outcomes. 

It's important to consider and explore the impact of the immune system within the bio-psychosocial model in psychiatry to provide patients with a better understanding of their condition and tailor treatments for improved outcomes. Thank you.