Refining the Construct of Resilience and Identifying Structural Neural Markers of Resilience in Young People

: (Alternative Format Thesis)

Abstract

It is estimated that over a third of the population worldwide experience childhood adversity, such as childhood maltreatment or parental loss (Green et al., 2010). Although adversity exposure is associated with mental health problems, many individuals exposed to adversity will remain resilient which, broadly speaking, means that they maintain adaptive functioning, including remaining free of or recovering quickly from mental health problems (Kalisch et al., 2017, 2021; Luthar et al., 2000). There has been an increase in research on resilience over the past half a century; however, there is still no clear consensus on how resilience should be defined, operationalised, or measured. Furthermore, there have been calls to increase our knowledge of the neurobiology of resilience (Curtis & Cicchetti, 2003), particularly in child and adolescent samples, given that childhood and adolescence are sensitive periods for brain development (Belcher et al., 2021).

Based on this, the current thesis had three aims. The first aim was to conduct a systematic review to establish how resilience in young people is related to brain structure, function, and connectivity. The second aim was to generate a new data-driven approach to defining and operationalising resilience using data on lifetime adversity exposure and psychopathology from a sample of high-risk youth. The third aim was to apply our data-driven, dimensional resilience scores to structural magnetic resonance imaging (MRI) data to examine how resilience is related to brain structure, and whether associations between resilience and brain structure differ between the sexes. These aims were achieved by using data collected from young people who took part in a European multi-site study, the Neurobiology and Treatment of Adolescent Female Conduct Disorder (FemNAT-CD).

The current thesis begins with a systematic review of 22 studies examining how resilience in young people is related to brain structure, function, and connectivity. The review identified that structurally, resilience was related to increased grey matter volume in frontal regions and altered hippocampus and amygdala volume. Functionally, resilience was associated with tighter coupling of a PFC-amygdala circuit and lower amygdala reactivity to emotional stimuli. Finally, resilience was associated with increased corpus callosum connectivity. Taken together, these findings suggest that enhanced emotion regulation is associated with resilience in young people. Common limitations of previous studies, such as the use of narrow and categorical definitions of resilience, were discussed.

In the first empirical study, we derived multidimensional, continuous resilience scores for a sample of high-risk youth (N=633). Data on exposure to adversity and lifetime psychopathology were entered into two factor analyses. Factor scores were weighted, aggregated separately for adversity exposure and psychopathology, and entered into a regression. Resilience scores were derived for each participant by calculating the individual distance from the regression line along the psychopathology dimension. A higher resilience score indicated that a person had lower levels of psychopathology than would be expected based on their level of adversity exposure. In line with previous research, resilience was positively correlated with IQ and socioeconomic status.

The resilience scores were then applied in the final two studies, which investigated a) how resilience is related to brain structure, and b) whether the relationship between resilience and brain structure differs between the sexes. The first used voxel-based morphometry (VBM) to examine relationships between resilience and grey matter volume across the brain. The second study used surface-based morphometry (SBM) to examine relationships between resilience and more specific properties of cortical structure (e.g., cortical thickness and gyrification), and subcortical volumes.

In the VBM study, across the whole sample (N=298), resilience was positively associated with higher grey matter volume in frontal and parietal regions. In the SBM study, across the whole sample (N=286), resilience was associated with increased surface area in the lateral occipital, decreased surface area in the inferior parietal, and increased gyrification in the superior frontal gyrus. Sex differences in the relationship between resilience and brain structure were identified in both studies, particularly in frontal and temporal regions. Neither study showed a relationship between resilience and hippocampal or amygdala volumes.

Overall, the current thesis demonstrated that it is possible to use data on exposure to adversity and lifetime psychopathology to derive multidimensional, continuous resilience scores for a large sample of young people. It is hoped that this method can be employed by other resilience researchers and clinicians moving forwards, to address what may be considered the primary limitation of resilience research. The current thesis also provides evidence that resilience is related to brain structure, function, and connectivity. In terms of brain structure specifically, resilience is positively associated with grey matter volume in frontal and parietal areas and alterations in surface area and gyrification in frontal, occipital, and temporal regions. Taken together, these findings suggest that brain areas involved in executive functions and emotion regulation are implicated in youth resilience. Finally, the relationship between resilience and brain structure may differ between the sexes. Therefore, it is plausible that there may be different pathways to resilience in males and females.

Date of Award	22 Feb 2023
Original language	English
Awarding Institution	University of Bath
Supervisor	Graeme Fairchild (Supervisor) & Catherine Hamilton-Giachritsis (Supervisor)