Neuroendocrine substrates of residual cognitive deficits in schizophrenia

Deficits associated with Hypothalamus-Pituitary-Adrenal axis anomalies are strikingly similar to the functional disabilities observed in schizophrenia. This is not surprising given the degree of overlap between this system and current neurophysiological models of the disorder. Recent models have been formulated for neuroendocrine involvement in the behavioral manifestations of schizophrenia. The present study examined possible neuroendocrine substrates of residual cognitive deficits in a chronic schizophrenia population. Participants were selected from an intensive biopsychosocial psychiatric rehabilitation program which provides pharmacological stabilization, behavioral modification programming, cognitive rehabilitation, and skill training groups. Due to the focus on residual cognitive deficits, actively psychotic patients were excluded from the study. Study participants completed a comprehensive battery of neuropsychological functioning including measures of abstraction, memory, spatial skills, attention, and preattention. Additionally, a comprehensive assessment of Hypothalamus-Pituitary Adrenal axis functioning was completed. This assessment consisted of stable trait-like functioning, including diurnal rhythm and response to dexamethasone. State functioning was also assessed with cortisol samples taken before and after neuropsychological testing sessions. The results indicated significant disruption of normal diurnal variation in cortisol production with some participants showing minimal change throughout the day. Residual deficits in verbal learning and verbal recall were associated with a particular pattern of neuroendocrine dysregulation characterized by abnormally high afternoon basal cortisol levels. No other domain of cognitive functioning was associated with any of the trait-like cortisol measures. However, performance on a component of the abstraction domain was associated with cortisol levels at the time of testing. This was the only cognitive measure associated with state functioning of the hypothalamus-pituitary-adrenal axis. The current study provides preliminary evidence for a link between neuroendocrine, dysregulation and residual deficits in cognitive functioning associated with chronic schizophrenia. The nature of this relationship and implications for further research and treatment are discussed