Hippocampal memory function over initial treatment period in first-episode psychosis: the role of stress and HPA axis functioning

Hippocampal dysfunction and structural abnormalities are commonly found in Schizophrenia. They are evident in the first episode of illness and have shown strong associations with functional outcome. However, the biological origins and stability of these deficits over the illness course remain unclear. One plausible hypothesis involves increased stress levels and dysfunction of the central cerebral region responsible for its regulation, the Hypothalamic-Pituitary-Adrenal (HPA) axis. Hippocampal function, particularly the ability to remember new associations, is highly sensitive to the neurotoxic effects of sustained increased cortisol levels. The aim of the current study was to test the stability of hippocampal function in drug-naı¨ve first-episode psychosis (FEP) patients over the first three months of treatment, and test possible relationships with biological measures of stress and HPA dysfunction. The performance of FEP patients and normal controls (NC) were compared using a novel memory task that included standard list learning and paired associated learning (PAL). At baseline, FEP patients (n = 26) were significantly more impaired on a list learning task than NC (n = 24) (P = .023), as well as on a hippocampal PAL task (P = .027). Further, FEP patients showed greater impairment on paired associates considered to be more abstract, which have been postulated to require greater hippocampal involvement. 12 FEP patients repeated the assessment after 3 months of treatment with an alternate form of the task, and showed a significant improvement in list learning performance that was not seen in NC (n = 18) (time X group interaction P = .019). Conversely, FEP patients continued to be impaired on PAL (P < .001) and there was no effect of or interaction with time (P = .447). These findings suggest that hippocampal dysfunction is stable over the first 3 months of treatment in first episode psychosis. Future analysis to determine possible associations between these findings and biological measures of stress and HPA axis activity (post-dexamethasone cortisol levels and glucocorticoid receptor function) will be incorporated as a part of this presentation.