Understanding the Relationship between Mental Health, Brain Structure and Socioeconomic Status in Older Adults

Abstract

Poor mental health is a global concern, particularly among older adults in the UK, where depression and anxiety are highly prevalent. These conditions often present differently in later life and are shaped by a complex interplay of biological, social, and psychological factors. Research indicates both disorders are associated with structural abnormalities in the brain, while social determinants—such as socioeconomic status (SES)—also play a substantial role in mental health outcomes. Additionally, some studies suggest that social factors may be linked to variations in brain structure. Despite the widespread acknowledgement of a biopsychosocial model of mental health, there is limited literature assessing these three factors simultaneously. This PhD project thus examined the relationships among depression and anxiety, a biological factor (brain structure), and social factors (namely SES). The thesis first reviews existing literature on the links between depression, anxiety, and brain structure among middle-aged and older adults. Chapter 2 establishes that several brain regions are relatively consistently implicated in depression, including the hippocampus, orbitofrontal cortex, prefrontal cortex, insula and temporal lobe. However, there is insufficient research on the relationship between anxiety and brain structure to determine which regions are consistently implicated in this disorder. Possible reasons for discrepancies in the literature in terms of brain regions and directions of effects, including variations in methodology and sample characteristics, are also explored. Following the review, the thesis utilises data from the UK Biobank (UKB), the largest global neuroimaging study, including data from middle-aged to older adults. This dataset is used to empirically investigate the relationship between depression and brain structure—specifically regional cortical volume—while also assessing the role of SES in this association. Chapter 3 presents findings showing that several brain regions, including the precentral, postcentral, supramarginal, angular and parahippocampal gyri, as well as the frontal and temporal poles, insular cortex and frontal orbital cortex, are associated with depression. However, many of these associations lose significance when SES is accounted for or when analyses are conducted separately by sex. The precentral gyrus emerges as the only brain region consistently associated with depression across all analyses. Next, the thesis progresses to examining the relationship between anxiety and brain structure, incorporating both cortical and subcortical volumes while again considering the role of SES. Chapter 4 presents findings indicating that the thalamus, parahippocampal gyrus, insular cortex, supramarginal gyrus and precentral gyrus are significantly associated with anxiety in a large UKB sample. However, all associations except for the precentral gyrus lose significance when SES is included in the analysis. When analyses are stratified by sex, no significant associations are found for females, while for males, the precentral gyrus remains associated with anxiety—but only in the model that excludes SES. This research enhances our understanding of how depression and anxiety relate to changes in brain structure in middle and older age while emphasising the critical influence of socioeconomic factors. The findings highlight the need to account for SES when studying mental health and brain structure, as failing to do so may lead to an incomplete or misleading picture. From a policy perspective, when combined with further research, these results have potential implications for efforts aimed at reducing mental health disparities. They suggest that interventions targeting individuals at higher risk of depression and anxiety—particularly those in lower SES groups—may be beneficial. Previous prevention programs have successfully reduced depression among children exposed to abuse and adults affected by conflicts or disasters. This raises the possibility that targeted prevention strategies for individuals with socioeconomic disadvantages could also be effective in mitigating the risk of depression and anxiety.

Date of Award	13 Jun 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Nicholas Shryane (Main Supervisor) & Caroline Lea-Carnall (Co Supervisor)