Abstract

BackgroundIndividuals with established psychosis are characterised by a distinct pattern of hypothalamic-pituitary-adrenal (HPA) axis dysfunctions which include both elevated daytime cortisol levels and a blunted cortisol awakening response (CAR). Whilst these patterns of dysfunction have also been observed among those at elevated risk for the disorder, longitudinal studies are scarce. As such, the relevance of these HPA axis abnormalities for the progression of psychopathology in high-risk populations is unknown. Utilising data from a well-characterised, longitudinal cohort of youth at elevated risk for schizophrenia and their typically-developing peers (The Child Health and Development Study), we aimed to investigate the extent to which HPA axis function determined in childhood is a significant predictor of putative prodromal status and psychopathology in late adolescence/early adulthood.MethodsThe sample comprised high-risk individuals who presented either multiple antecedents of schizophrenia (developmental delays, psychopathology, and psychotic-like experiences: ASz=21) or a family history of illness (FHx=13), and typically-developing youth with neither antecedents nor a family history (TD=36). Participants were recruited at age 9–12 years using a community screening method and assessed biennially throughout adolescence. At the age 11–14 years assessment phase, participants collected salivary cortisol samples in their home environment which were used to determine diurnal cortisol secretion and the CAR. At the age 17–21 years assessment phase, participants completed measures of prodromal symptoms (Prodromal Questionnaire: PQ), depression (Quick Inventory of Depressive Symptomatology questionnaire: QIDS), and anxiety (Social Interaction Anxiety Scale: SIAS). Established PQ thresholds were used to identify participants who met probable prodromal status. Logistic and linear regression analyses were used to examine the extent to which salivary cortisol measures at age 11–14 years predicted probable prodromal status and continuous psychopathology measures at 17–21 years, respectively.ResultsRelative to the TD group, ASz youth were characterised by higher depression (B=0.24, p=0.05) and disorganised symptoms (B=0.36, p=0.007) at 17–21 years whilst FHx youth obtained higher scores on the PQ general symptoms scale (B=0.24, p=0.048). Analyses performed in the total sample indicated that the CAR was negatively associated with depression symptoms (B=-0.28, p=0.006) and PQ negative symptoms (B=-0.30, p=0.004) at age 17–21 years. Positive associations were observed between diurnal cortisol and positive (B=0.41, p=0.02), disorganised (B=0.30, p=0.04), and general (B=0.29, p=0.03) PQ symptoms. Diurnal cortisol levels were also significantly associated with probable prodromal status at follow-up (OR=1.04, p=0.04). No significant interactions were observed between group status and salivary cortisol levels in any model. After adjustment for potential confounders (age, follow-up time, sex, BMI, and pubertal status), the CAR continued to show significant associations with both depression (p=0.006) and PQ negative symptoms (p=0.007) whilst only a statistical trend was observed for the relationship between diurnal cortisol levels and positive symptoms (p=0.055).DiscussionThe current study is the first to examine the extent to which HPA axis function can predict development of prodromal symptoms in a high-risk cohort. Our finding that more abnormal HPA axis function (i.e., a decreased CAR and higher diurnal cortisol) at age 11–14 years is associated with both prodromal and depression symptoms at age 17–21 has important implications for aetiological theories and for clinical practice.

Highlights

  • There is a cumulative evidence for increased level of markers of inflammation in psychosis, it has not been conclusively proven yet whether this is due to the disorder in itself or to other factors

  • The Body Mass Index (BMI), as an indirect measure of body fat level, and tobacco smoking are known to play a role in modulating the immune system, but little research has been done in this area in patients with psychosis

  • There was no significant difference in IL-6, IL-8 and Brain-Derived Neurotrophic Factor (BDNF) serum levels between the two groups

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Summary

Background

A factor structure similar to the one observed in schizophrenia has been unraveled, being the positive and negative the most consistently replicated dimensions. Despite this fact, most of the studies on brain volume patterns in schizotypy consider it as an unitary rather than a multidimensional construct. Based on previous results showing that schizophrenia and schizotypal personality traits share common

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