Major depressive disorder (MDD), is a major medical and economic burden for today's society. About 30% of MDD patients develop treatment-resistant depression - TRD with the related sequelae in terms of worse prognosis. If several risk factors can be assessed readily on presentation, it can guide treatment planning and ultimately improve clinical outcomes. Currently, unlike other areas of medicine, poly-risk tools to facilitate this stratification in practice among patients with MDD are lacking but demanded in the era of personalised/precision medicine - a challenge that the project takes up. Ketamine - a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is the first exemplary agent with rapid (within hours) antidepressant effects, even in TRD patients.Its mechanisms of actions (MoA) are still unclear but greatly demanded. So far, insights about ketamine's MoA come from preclinical animal studies but it's known that animal models have limited ability/effectiveness in mimicking the clinical complexity and were not subjected to sequential application of different treatments - a key requisite in humans to be defined as TRD. This ambitious inter/multidisciplinary project, has 3 goals: 1. To develop a clinical risk stratification tool for predicting TRD development. 2. To unravel ketamine's fast-acting antidepressant mechanisms of action (MoA) on mature neurons obtained from human induced pluripotent stem cells (iPSCs) obtained from (ketamine-responsive \& non-responsive) patients with TRD. 3. To give maximum visibility to the project and spreading its contents \& findings to and in a way understood by all target groups variously implicated/interested in project research \& innovation.
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Create in vitro human cellular models of some drug-resistant psychiatric disorders.
Timeframe: Entire study duration (approximately 10 years)