The interaction of risk and protective factors for mental disorders on psychopathology and brain morphometry

As per the diathesis-stress model, combined early risk factors (diathesis) and current risk factors (stress) determine an individual’s likelihood for the development of psychopathology. If the combined impact of diathesis and stress surpasses a certain threshold, individuals will develop psychopatho...

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Bibliographic Details
Main Author: Brosch, Katharina
Contributors: Kircher, Tilo (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2022
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Summary:As per the diathesis-stress model, combined early risk factors (diathesis) and current risk factors (stress) determine an individual’s likelihood for the development of psychopathology. If the combined impact of diathesis and stress surpasses a certain threshold, individuals will develop psychopathology. At the same time, such threshold could be raised in the presence of protective factors, as they buffer the negative impact of risk factors, and lead to a reduced likelihood of developing psychopathology. Early risk factors for mental disorders include trait anxiety, childhood maltreatment and familial risk, and have been associated with specific brain morphometric alterations. Stressful life events, including the Covid-19 pandemic as a global example of that, constitute current risk factors. On the other hand, current literature suggests social support and conscientiousness as exemplary protective factors. These may increase resilience, a concept describing an individual’s ability to adaptively cope in the face of adversity and maintain mental health. However, contrary to risk factors, neural correlates of resilience are only sparsely known and hardly understood. Thus, to make precise predictions about the emergence of psychopathology in certain circumstances and understand possible neurobiological pathways, it is essential to jointly consider both risk and protective factors in mental health research. The aim of this dissertation was to investigate the interaction of risk and protective factors in three different but complementary contexts to gain a deeper understanding of these factors and their impact on brain morphometry and psychopathology. In STUDY I, morphometric correlates (specifically grey matter volume) of resilience were investigated. In this study, resilience was conceptualized as the maintenance of mental health despite a high risk (i.e., childhood maltreatment and familial risk). A key finding is that healthy high-risk individuals demonstrated larger grey matter volume in the left dorsolateral prefrontal cortex, an area associated with cognitive flexibility and emotional regulation skills, compared to the other groups. It seems plausible that an increased volume in this area is a neural correlate of resilience to high risk and may represent compensatory processes aiding high-risk individuals in maintaining mental health. STUDY II approached the subject in the opposite way, with transdiagnostic grey matter volume alterations in psychiatric patients compared to healthy subjects being associated with risk and protective factors. This study identified reduced volume in the left hippocampus as a transdiagnostic vulnerability marker in patients with major depression, bipolar disorder, and schizophrenia spectrum disorder. Volume in this area was further negatively associated with stressful life events, and executive and global functioning in both patients and healthy subjects. We conclude that stressful life events likely constitute a dimensional risk factor for reduced hippocampal volume and, therefore, are independent of diagnosis. STUDY III investigated the impact of a unique, acute global stressor, the Covid-19 pandemic, on healthy subjects and transdiagnostic patients. Multiple trait risk and protective factors were tested for their explanatory value of current Covid-19-related fear and isolation. This study identified trait anxiety and conscientiousness as risk factors for increased Covid-19-related fear, and social support as a protective factor against increased Covid-19-isolation. Again, the respective effect (harmful or protective) of all these factors was dimensional, i.e., relevant in both psychiatric patients and healthy subjects. STUDY III also highlighted the context-dependency of risk and protective factors: although generally considered a protective trait, increased conscientiousness was harmful in the context of a global pandemic due to the immense level of uncertainty and unpredictability. In conclusion, this dissertation identified brain correlates as potential biomarkers of psychopathology and resilience, and procedural contributors to adaptive and maladaptive responses to acute stressors. It highlighted the importance of taking protective factors, in addition to risk factors, into account in research. A major strength is the integration of multiple risk and protective factors, as such integrative approaches are crucial to advance the understanding of their complex interplay. By identifying dimensionality and context-dependency as important modulatory influences in the risk and protective factor interplay, it provided a framework for a more comprehensive understanding of the development of psychopathology, and the concept of resilience as a dynamic, continuous process of adaptation to changing environments, which enables individuals to maintain mental health even in the face of adversity.
Physical Description:91 Pages