Early life stress is a major societal problem due to the unacceptably high prevalence that transdiagnostically increases risk to psychopathology. Neuroglia, meaning "nerve glue," are crucial for holding the brain together, shaping its intricate structure and function. Consequently, neuroglia are implicated in various psychopathologies that involve global dysfunction, including schizophrenia, depression, and bipolar disorder. Animal and cell studies have shown that neuroglia are highly stress-responsive, and alterations to their function generates psychiatric-like symptoms. However glia are relatively understudied in humans, presenting a critical knowledge gap given glia are often poorly conserved between rodents and humans. My lab has been combining single-cell RNA sequencing, spatial transcriptomics, and advanced histological approaches to characterise human neuroglia and how they are impacted by stress and in psychopathology. We examine postmortem samples from individuals across a range of psychiatric disorders exposed to childhood versus adulthood stress, as well as 2D and 3D human pluripotent stem cell-derived glia treated with dexamethasone, a cortisol analogue, to mimic the stress response in a dish. In this presentation, I will give an overview of our work focusing on characterising astrocytes and microglia in the human prefrontal cortex. Our studies have shown, for the first time, that there are many subtypes of molecularly-defined astrocytes. Furthermore, these astrocyte subtypes in combination with previously defined microglia subtypes, are overrepresented in individuals with transdiagnostic psychiatric disorders exposed to stress in childhood. Lastly, our data suggests that changes in astrocytes and microglia may culminate in neuropathologies related to neuroinflammation and the blood brain barrier.