Approved research

The Association of Brain Morphology and Mental Health with Neighborhood Environment

Lay summary

The social and physical environments play a role in the variability of brain structure as well as the development and prevalence of mental disorders. In particular, the socioeconomic environment, neighbourhood mean income and income-inequality, can serve as a stressor impacting brain health. Moreover, one's physical neighbourhood environment can result in exposures that impact the brain. Air pollution is a growing concern in today's societies especially from an environmental perspective. Pollution can impact the brain resulting in alterations in brain structure and increasing the risk for mental disorders. Therefore, the aim of this investigation is to determine the association between neighbourhood socioeconomic indicators and exposure to air pollution with brain structure and function. Income and Income-inequality are related to altered brain structure and rates of mental illness. It is thought that stress may be the mechanism by which this relationship takes hold. Therefore, we will investigate how exposure to these potential neighbourhood stressors may alter the brain and mental health in individuals of the UK Biobank. All individuals around the world are exposed to varying degrees of air pollution. Pollution is not only harmful to the environment but to our brains and bodies as well. Pollutants in the air can trigger brain inflammation and result in brain structure alterations akin to Alzheimer's as well as lead to potential risk of mental illness. It is for these reasons air pollution is a growing concern for brain health and we propose to study this relationship further in our investigation. To carry out this project, we will require data from the full UK Biobank sample with access for approximately 3 years. Ultimately this investigation will aid in the understanding of how the human social and physical environment impact brain structure and function.

Current scope:

The environment, both social and physical, impacts human brain structure and function. To date, investigation into the relationships between environment and the brain has been heavily focused on large geographic areas (cities, states, countries), rather than neighbourhood-level exposures. Also, there has been no investigation of a general psychopathology factor in association with environmental exposures. Therefore, we aim to (1) investigate associations between neighbourhood-level stressors and several brain-related outcomes, and (2) investigate potential underlying mechanisms of these associations. We will investigate two neighbourhood-level stressors: socio-economic and environmental. The former will include income inequality and mean income, and the latter will include local air pollution. Brain-related outcomes will include structural morphology, which we will derive from T1-weighted brain MRIs, and a general psychopathology factor, which we will derive from questionnaires on mental health symptoms. To investigate underlying stress and inflammatory mechanisms, mediating roles of indicators such as stressful/traumatic life events, individual socioeconomic status, and blood levels of inflammatory markers (e.g., C-reactive protein) will be tested. Ultimately, this project will allow for a better understanding of how the human brain and behaviour is shaped by the environment.

In addition to our original research scope, we hope to elucidate the genetic and molecular architecture of psychopathology (and related traits) in relation to ones social environment. Any polygenic scores and/or new phenotypes derived from the provided genetic data will be returned to the UK Biobank.

To elucidate potential systemic inflammatory mechanisms that may be related to brain health, we will also investigate abdominal MRI metrics previously associated with inflammation.

The brains white matter is often implicated in stress related exposures. Therefore, we hope to expand our investigation beyond structural brain metrics derived from T1-weighted images to include metrics from T2-FLAIR and dMRI.

Extended scope:

Multiple sex (biological) and gender (environmental) differences have been reported for both systemic and brain phenotypes. Here we hope to investigate genetic and polyphenotypic sex variations in systemic inflammation (and related cardiometabolic) traits that may be impacting brain-structure MRI phenotypes.

It is recognized that brain structure is influenced by multiple factors throughout the lifespan. Here we would like to investigate a role of fetal growth-related factors in adult brain structure. For this analysis, we will employ polygenic scores of birthweight, a proxy of fetal growth, which can be partitioned into two statistically independent components, (1) fetal variants associated directly with the fetal birthweight; and (2) maternal variants influencing the intrauterine environment and, in turn, the growth of the fetus.

Scope extension:

Chronic diseases, such as chronic low back pain, Parkinson's disease, stroke and osteoarthritis, are highly prevalent in all populations, particularly the elderly. Chronic diseases could result in pain, disability, mental impairment, low quality of life and even death, thereby producing an enormous economic burden. Therefore, it is significant to knowledge about the potential predictors and factors for chronic disorders to prevent their incidence, improve their symptoms, and avoid mortality.

The overall goal of this project is to explore the associations of chronic diseases with physical activities, muscle strength, lung function and cognitive function. The project primarily aims to provide the relations of all-cause chronic disease incidence and mortality with physical activity and muscle strength, which will help to explain the role of physical fitness in the prevention, development, and deterioration of chronic disorders. Second, the project will demonstrate the associations of chronic diseases with lung and cognitive functions, which can indicate the potential influence of lung and cognition on the incidence and mortality of chronic disorders.

Additionally, the association between chronic diseases with unhealthy lifestyles, such as smoking and alcohol consumption, is also investigated to better develop targeted public health interventions. Recognizing the connection between certain lifestyle choices and chronic diseases emphasizes the importance of preventive healthcare. Individuals can be educated about the risks associated with smoking and excessive alcohol intake, empowering them to make informed decisions and adopt healthier lifestyles to prevent the onset of chronic diseases.