Speaker: Associate Professor Susannah Tye
Queensland Brain Institute
University of Queensland
Title: Immunometabolic Control of Dopamine Circuits: Translational Biomarkers and Novel Therapeutic Pathways in Treatment-Resistant Depression
Abstract: Dopamine circuits are highly sensitive to immune and metabolic stress, and accumulating evidence indicates that disturbances in cellular energetics are a fundamental driver of antidepressant treatment resistance, impaired motivation, and chronic fatigue in mood and related brain disorders. In this presentation, I will integrate mechanistic insights from our preclinical stress and antidepressant-response models with new findings from the US National Network of Depression Centers’ Bio-K clinical trial to demonstrate how deficits in mitochondrial respiration, glycolytic flexibility, and ATP-linked signalling map onto therapeutic response to ketamine. Complementary laboratory work has further identified prefrontal purinergic inputs to the nucleus accumbens as stress-sensitive modulators of corticostriatal dopamine network dynamics, implicating ATP and adenosine signalling as key regulators of behavioural adaptation. I will discuss how stress-susceptible, energetically compromised states are coordinated across central and peripheral systems, mediated in part by immune activation and immunometabolic adaptation, to reshape dopamine-dependent motivated behaviour. We and others posit that such responses may have conferred evolutionary advantage by promoting rest and recovery through resource conservation, but that in contemporary environments, these mechanisms contribute to disabling and treatment-refractory neuropsychiatric symptoms. Together, these multimodal datasets provide a mechanistic foundation for precision antidepressant treatment and define actionable biomarkers that can guide drug development, patient stratification, and adaptive neurotherapeutic device strategies. Collectively, this work outlines a translational pathway toward metabolically informed, personalised interventions for treatment-resistant depression that directly link cellular energetics to circuit function and clinical outcomes.
About Neuroscience Seminars
Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.
Seminars in the QBI Auditorium on Level 7 are held on Wednesdays at 12-1pm, which are sometimes simulcast on Zoom (with approval from the speaker). We also occassionally hold seminars from international speakers via Zoom. The days and times of these seminars will vary depending on the time zone of the speaker. Please see each seminar listed below for details.
