B4254 - Investigating the impact of environmental and lifestyle factors across development on hippocampal neurogenesis and depression - 11/08/2023

B number: 
B4254
Principal applicant name: 
Andrea Du Preez | King's College London (United Kingdom)
Co-applicants: 
Title of project: 
Investigating the impact of environmental and lifestyle factors across development on hippocampal neurogenesis and depression
Proposal summary: 

Depression is a debilitating condition that significantly impacts on the physical, emotional, and social wellbeing of individuals and their relatives. Unfortunately, effective treatments for depression are struggling to keep up and we need to seek other ways of supporting and treating those at risk. However, we first need to more fully understand how the various risk and protective factors for depression might be working on a more biological level.

One key brain region associated with depression is the hippocampus, which is also where hippocampal neurogenesis (HN, i.e., the birth of new neurons) occurs. It is a key form of brain plasticity, vital for learning and memory, responding to stress, and regulating emotions. Importantly, depression has been associated with changes in HN, which is thought to occur throughout life in response to important social and health factors including diet, exercise, stress, and inflammation – all also key risk and/or protective factors for depression.

Until now, it has been impossible to test the effects of these factors on human HN. However, using an in vitro neurogenesis cellular assay (which involves adding participant serum to human hippocampal cells) we can generate proxy readouts of neurogenesis for each individual and then explore of how key risk and protective factors for depression influence these HN readouts.

As such, this Fellowship project will look at the relationship between HN and depression and explore the impact of key risk and protective factors for depression on neurogenesis across early life.

Impact of research: 
Completion of this study will have (i) elucidated the relationship between neurogenesis and depression across early life through to early adulthood, (ii) determined which risk and protective factors for depression mediate/modulate neurogenesis (and depression) outcomes, (iii) identified genes differentially expressed in those with/without depression focusing on neurogenesis - all to (iv) provide the scientific foundations for future evidence-based recommendations for lifestyle and/or educational interventions aimed at preventing/slowing down the impact of depression with neurogenesis as a possible target of choice. This work gives rise to two major strengths. First, through the use of the ALSPAC cohort, the cumulative impact of important health, social, and biological risk factors across the life course can be investigated and this specific project adds to this by providing information on neural plasticity (that is currently lacking), which is a key biological process that is affected throughout life by a wide range of environmental and genetic factors. Providing information on this biological process could, therefore, generate new ideas/perspectives and help the field to understand more fully depression aetiology and/or some of the mechanisms that might be driving or influencing depression outcomes. Moreover, given the longitudinal nature of the project, the most critical stages in life, where changes in neurogenesis may be most important, could be identified. Second, the outcomes of this project could aid prevention and treatment by helping the field identify how and when to intervene. Should neurogenesis outcomes play a critical role in the development of depression in later life, this could then be used as a target of choice, and the field could then focus on environmental factors, particularly lifestyle factors, that then promote “healthy” neurogenesis. This could also be tailored to maximise the effect, e.g., during childhood, by focusing on factors at this life stage that may be particularly beneficial, e.g., schooling and education.
Date proposal received: 
Friday, 10 February, 2023
Date proposal approved: 
Friday, 17 February, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, Cell culture, Computer simulations/modelling/algorithms, Microarrays, RNA, Statistical methods, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Intelligence - memory, Metabolic - metabolism, Nutrition - breast feeding, diet, Parenting, Physical - activity, fitness, function, Statistical methods, Birth outcomes, BMI, Childhood - childcare, childhood adversity, Cognition - cognitive function, Development, Epigenetics, Hormones - cortisol, IGF, thyroid, Immunity