Stress in schizotypy: Interactions with (epi)genetics, life events, and resilience
Creators: name: Trischel, Ksenia
Publisher: name: University of Lincoln
Year: 2024
Subjects: C800 - Psychology

description: Schizophrenia and psychosis-spectrum disorders are devastating for the affected individual and pose a considerable burden on society. High levels of schizotypy, a collection of traits such as unusual perceptual experiences, cognitive disorganisation, and social anhedonia, have long been recognised as risk factor for the development of schizophrenia, with a substantial prevalence of high schizotypy observed in non-clinical population. Psychological and physiological stress reactivity have been identified as potential mechanisms for moderating vulnerability for the development of psychopathology, leading to the proposal of the diathesis or vulnerability-stress model of schizophrenia. However, only little research exists assessing the stress response in schizotypy,exposing a gap in our understanding of the interactions between factors of vulnerability and resilience in schizotypy.Therefore, this thesis aimed to comprehensively explore the relationship between schizotypy levels in non-clinical populations and the core vulnerability-stress model factors such as genetic riskrepresented by minor haplotype of FKBP5 (a gene associated with endocrine stress response),epigenetic markers such as methylation levels of FKBP5, early life adversity, chronic stress, as well asresilience factors, such as perceived levels of resilience and coping strategies. In a set of five studiesperception of early life stressors, recent life stressors, acute laboratory stressor (Trier Social Stress Test), chronic stressors, and a real-life stressor (COVID-19 pandemic) as well as perceived resilience and coping preferences were investigated in the context of schizotypy. For the first time, not only acute salivary cortisol levels but also chronic levels of cortisol, DHEA and of other related steroids were measured in hair of individuals preselected for high and low schizotypy, using the state-of-the-art techniques such as ELISA and LC-MS/MS.Overall, and in line with the initial hypotheses, high schizotypy levels, in partial interaction with genetic predisposition and environmental adversity, were associated with higher stress sensitivity and poorer stress management than low schizotypy levels. This was characterised by attenuated physiological and increased psychological response to acute and chronic stressors, as well as perception of higher vulnerability and lower resilience. Increased stress perception was associated with all schizotypy subscales. All but negative schizotypy subscales were associated with acute and chronic cortisol response. A prospective-design study over six months identified the increased use of maladaptive coping strategies to mediate the relationship between schizotypy and levels of depression and anxiety. Contrary to the hypothesis, no direct genetic effect of stress-associated genotype of FKBP5 or FKBP5 methylation on schizotypy were found. However, an interaction effect between minor FKBP5 haplotype and childhood trauma showing lower schizotypy levels was observed, suggesting a potential protective effect of minor FKBP5 haplotype in the context of low to moderate early adversity.Based on these findings, an extended vulnerability-stress model of stress response in schizotypy was proposed to incorporate possible molecular and behavioural mechanisms. Thus, the present thesis contributes to a more comprehensive understanding of the relationships between schizotypy, stressresponse, and resilience. This knowledge might facilitate future development of more individualised and targeted interventions to improve stress management in high schizotypy and lower vulnerability to developing psychosis in some individuals.