stress and HPA-axis Research Prpgram (SHARP) study, Melbourne Neuropsychiatry Centre

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Stress and abnormal functioning of the hypothalamic-pituitary-adrenal axis (HPA) axis have been reported in patients with schizophrenia and other psychotic disorders. Prolonged exposure to elevated levels of cortisol (the end product of HPA axis activity) has potential detrimental effects on the brain including damage to the hippocampus and prefrontal cortex, as well as memory impairment. Elevated stress and/or abnormal HPA function in patients with acute psychosis has been proposed to contribute to symptom severity and structural brain changes observed in psychotic disorders 1. However, due to the lack of prospective, longitudinal studies in drug naïve first-episode psychotic (FEP) patients, the effect of HPA dysfunction on symptoms and dynamic brain changes in early psychosis remains unclear. The current project aims to longitudinally investigate the relationship between stress, HPA function, symptom severity, cognitive performance, medication compliance and structural and metabolic brain changes in neuroleptic-naïve or minimally treated FEP patients during the initial 3 months of treatment. It is hypothesized that: a) At baseline, FEP patients will display abnormal HPA axis function, poorer coping mechanisms, heightened levels of perceived stress and reduced neuronal integrity compared to healthy matched control subjects b) Treatment with an atypical antipsychotic will normalize HPA dysfunction in FEP patients and this normalization of HPA axis activity will be associated with an improvement in symptoms, cognitive performance and no change in hippocampal and prefrontal cortical volume c) FEP patients with persistent abnormalities in HPA function after 3 months of treatment will have more severe symptomatology, a greater degree of cognitive impairment and a greater degree of cortical grey matter loss (particularly in prefrontal and hippocampal brain regions) d) Non-compliance or low levels of compliance with antipsychotic medication during the initial 3 months of treatment will be associated with a greater degree of cortical grey matter volume loss e) FEP patients with pets will have better improvements in psychotic and affective symptoms, and have a greater sense of social support and internal locus of control compared to healthy matched controls. Biological measures of HPA function, psychopathology, medication compliance, neurocognition, life events/daily hassles, perceived stress, coping style, social support, locus of control, pet attachment, experience of trauma, Magnetic Resonance Imaging (MRI) and MR Spectroscopy (MRS) brain scans. were obtained from 55 FEP patients who were neuroleptic-naive or received ≤7 days psychotropic medication (prior to initial blood sample) and 40 healthy-matched control subjects were recruited at baseline or upon initial intake into EPPIC. A proportion of patients and controls were followed up at the 3-month time-period. Time period: 2006-2009