Melbourne School of Psychological Sciences - Theses

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    Empathy during childhood; an investigation of associations with anxiety and depressive symptoms, and brain structure and function
    Bray, Katherine Olivia ( 2021)
    This thesis investigated the associations between empathy and internalising (i.e., depressive and anxiety) symptoms, and the underlying structural, and functional connectivity neural correlates of empathy in late childhood. Background: Empathy refers to the understanding and sharing of others’ emotions, is a multidimensional construct, and includes cognitive and affective components. Empathy is important for social functioning, and alterations in empathy have been demonstrated in many developmental/psychiatric disorders. Studies in adults have demonstrated that both cognitive and affective empathy are associated with internalising symptoms. Studies in adults have also examined the neural underpinnings of empathy, implicating two major functional brain networks: the Default Mode Network (DMN) has been implicated in cognitive empathy, while the Salience Network (SN) has been implicated in affective empathy. These findings have mostly resulted from investigating brain activity during empathy tasks (i.e., in functional Magnetic Resonance Imaging [fMRI] studies). Less research has examined the associations between trait empathy, and brain structure or intrinsic functional connectivity. Few studies have investigated these associations between empathy and either internalising symptoms or the neural correlates in young people, particularly children. Investigating associations between empathy, mental health, and brain structure and function during childhood is beneficial to begin to build a comprehensive picture of the development of empathy components and the neural correlates of empathy across the lifespan. Based on previous research in adults and preliminary work in children, we hypothesised that higher levels of empathic distress and lower levels of cognitive empathy would be associated with higher depressive and anxiety symptoms (particularly social anxiety symptoms). We also hypothesised that children’s cognitive and affective empathy would be associated with individual differences in brain structure and function within areas related to the DMN and the SN, respectively. Methods: Participants were 9- and 10-year-old children, a subset from the second wave of the Families and Childhood Transitions Study (FACTS), a longitudinal, community-based cohort study. Sample size across the empirical chapters of the thesis differed depending on measures completed and quality of brain images (study 1 n =127, study 2 n = 125, study 3 n = 112). Self-report measures of empathy (cognitive empathy, affective empathy: affective sharing, empathic concern, empathic distress) and internalising (anxiety and depressive) symptoms were administered, as well as a task-based measure of cognitive empathy. To investigate associations between empathy and internalising symptoms (study 1), canonical correlation analysis (CCA), a multivariate technique, was employed. Participants underwent MRI of the brain where T1-weighted structural images and resting-state functional sequences were collected. Grey matter volume, cortical thickness (study 2), seed-to-whole-brain and dual regression resting-state functional connectivity (study 3) were examined. Results: Study 1: CCA demonstrated that components of affective empathy, specifically affective sharing and empathic distress, were associated with internalising (particularly social anxiety) symptoms. Cognitive empathy was not associated with internalising symptoms. Study 2: In region of interest analyses, individual differences in affective and cognitive empathy were related to grey matter volume in the insula and the precuneus. Although these associations were of similar strength to those found in previous research, they did not survive correction for multiple comparisons. While no associations were detected between grey matter volume and empathy in exploratory whole-brain analysis, associations were found between empathic concern and cortical thickness in the right precentral gyrus. Study 3: Seed-to-whole-brain resting-state functional connectivity analyses demonstrated that both affective sharing and empathic distress were associated with decreased connectivity between key hubs of the DMN (precuneus and temporal parietal junction) and other widespread areas in the brain. Analyses of resting-state networks demonstrated that cognitive empathy was associated with both increased and decreased connectivity between dorsal and lateral regions of the DMN and regions outside of the DMN, including the pre- and postcentral gyrus, and the cerebellum. Affective empathy was associated with increased connectivity between the anterior SN and the pre- and postcentral gyrus. These relationships did not survive strict correction for multiple comparisons. Conclusions: Findings suggested that children who share others’ emotions strongly are more likely to experience anxiety, particularly of a social nature. This study also provided preliminary evidence that individual differences in self-reported empathy in children may be related to certain aspects of brain structure and functional connectivity. Overall, we observed less clear dissociations between the neural correlates of affective versus cognitive empathy, and more widely spread involvement from other brain areas. This potentially indicates reduced maturation and specialisation of the systems underlying affective versus cognitive empathy in this age group. However, more research is required to demonstrate reproducibility of the findings. More research investigating the mental health associations and neurobiological correlates of empathy in children is needed, particularly of a longitudinal nature, to track these changes across development. One limitation of our study is that the majority of our findings were based around self-report measures of empathy, which may not accurately reflect empathic ability.
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    Bugs and Brains: The Gut and Mental Health Study Characterising the gut microbiota in anxiety, depression, irritable bowel syndrome, and their comorbidity
    Simpson, Carra Aven ( 2021)
    Background: The community of microorganisms inhabiting the gastrointestinal tract, collectively known as the gut microbiota, is intimately involved in the maintenance of host health. Comprehensive characterisation of the gut microbiota may enable us to better understand conditions whose pathophysiologies remain poorly understood, including internalising mental health disorders (anxiety and depressive disorders) and irritable bowel syndrome (IBS). While existing research has sought to characterise the gut microbiota in these conditions, the two systematic reviews included within this thesis reveal that studies have failed to consider essential confounders, including age, dietary intake, medication use, biological sex, and body mass index. The inadequate consideration of IBS and internalising disorder co-occurrence was also highlighted. Accordingly, this thesis aimed to investigate the gut microbiota in medication-free females with either IBS or an internalising disorder, as well as females with comorbid IBS and anxiety/depression, whilst controlling for key covariates (age, dietary intake, body mass index). Study 1 aimed to compare the gut microbiota of females with IBS relative to controls, as well as compare microbial composition between the three major IBS subtypes (IBS-diarrhoea, IBS-constipation, IBS-mixed). Study 2 aimed to characterise the gut microbiota of females with an internalising mental health disorder relative to controls. Study 3 aimed to compare and contrast the gut microbiota of females with comorbid IBS and an internalising disorder to controls, as well as to participants with IBS or an internalising disorder separately. Method: This thesis includes 162 females, recruited as part of the Bugs and Brains Study, who belonged to one of four groups: i) 42 controls; ii) 36 participants with an internalising disorder (depressive/anxiety disorder), but no IBS; iii) 42 participants with IBS, but no internalising disorder and iv) 42 participants with both an internalising disorder and IBS. Participants completed comprehensive questionnaires, attended a clinical mental health interview, collected a stool sample, and had their anthropometrics measured within a 1-month period. The gut microbiota was estimated using 16S rRNA gene sequencing on an Illumina MiSeq platform (V4 hypervariable region). Sequences were pre-processed using QIIME2 and following the DADA2 denoising pipeline to produce amplicon sequence variants (ASVs). ASVs were taxonomically assigned against the SILVA database (v.138). Data analysis was performed using R (v.1.3.1073), with the packages phyloseq and picante (alpha diversity), vegan (beta diversity), ANCOM-BC and MaAsLin2 (differential abundance), and randomForest (random forests). Results: Comprehensive multivariate analyses revealed key similarities with regards to the gut microbiota in IBS and anxiety/depression relative to controls. Females with IBS or an internalising disorder tended to be enriched in bacterial species associated with inflammation (e.g., Proteobacteria, Parabacteroides, Alistipes), and participants with either condition harboured a lower relative abundance of immunoregulatory SCFA-producing bacteria relative to controls (e.g., Barnesiella, Bacteroides eggerthii, Lachnospira, Faecalibacterium). Moreover, both the anxiety/depression and IBS groups had higher relative abundances of species known to degrade the essential amino acid tryptophan (i.e., Alistipes). While similar findings were observed in participants with comorbid anxiety/depression and IBS, the gut microbiota composition in this group was heterogeneous, and alterations were not more pronounced than those observed in participants with either disorder separately. Of note, higher abundances of mucin-degrading bacterial taxa were observed in IBS-C and IBS-M relative to controls and the IBS-D group (e.g., Akkermansia muciniphila), suggesting this alteration may be a unique to constipation. Conclusion: This thesis presents a comprehensive characterisation of the gut microbiota in females with IBS, an internalising mental health disorder, and their comorbidity. Similar alterations in the gut microbiota composition relative to controls were identified in these conditions and were not driven by their comorbidity, as participants in the IBS group had no lifetime history of a mental health disorder, and participants in the anxiety/depression group had no lifetime history of IBS. The included studies have great strength in highlighting these findings independent of key confounding factors, including age, dietary intake, BMI, and host sex. Participants in this study were also medication-free and without relevant medical comorbidities. While these studies are well placed to examine the cross-sectional associations between gut bacteria with IBS and internalising disorders, future research should seek to integrate functional analyses and examine other microbial members of the gut microbiota. Longitudinal research designs that combine taxonomic and functional investigations will elucidate the true complexity of gut microbe interactions with host mental health and gastrointestinal functioning.