| Summary: | Background: Individuals with psychosis are characterised by increased exposure and reactivity to psychosocial stressors and abnormal hypothalamic-pituitary-adrenal (HPA) axis function [i.e., elevated cortisol levels, a blunted cortisol awakening response (CAR), and pituitary volume abnormalities]. The extent to which these features are present among at-risk individuals, prior to illness onset, is currently unclear. Aims: To determine whether putatively at-risk children who present multiple antecedents of schizophrenia (ASz) or a family history of illness (FHx) show increased susceptibility to psychosocial stressors and HPA axis abnormalities relative to typically-developing (TD) children. An additional aim was to explore associations between these measures and neurocognitive function. Methods: ASz (n=35), FHx (n=25), and TD (n=44) children were identified at age 9-12 years using a novel community-screening procedure or as relatives of individuals with schizophrenia. Measures of psychosocial stress, salivary cortisol, pituitary volume, and neurocognitive function were obtained at age 11-14 years. Results: Relative to TD children, both ASz and FHx children reported greater exposure to psychosocial stressors and were more distressed by these exposures (d=0.55-1.02, p<0.05). Additionally, FHx children, but not ASz children, showed a blunted CAR compared to TD children (d=0.73, p=0.01), yet neither group were characterised by elevated diurnal cortisol levels or pituitary volume abnormalities. In exploratory analyses, more abnormal HPA axis function (i.e., higher diurnal cortisol levels and a more blunted CAR) was associated with greater neurocognitive deficits among FHx and ASz children, whilst experiences of psychosocial stress were associated with better neurocognitive performance.
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