Background: In response to the rising mental health concerns and cognitive decline associated with the human brain’s neurogenesis, which continues until the tenth decade of life but declines with age and is suppressed by poor environments, this pilot study investigates how physical environments may influence public health proxy measures of neurogenesis in humans. This pilot study focuses on the residential environment where people spend most of their time and age in place, exploring the dependency of depression, anxiety, and cognitive impairment variations on spatial and lifestyle variables. Methods: A total of 142 healthy adults in England completed a survey consisting of PHQ-8, GAD-7, and CFI questionnaires and other questions developed to capture the variance in spatial and lifestyle factors such as time spent at home, house type layout complexity, spaciousness, physical activity, routine and spatial novelty, and perceived loneliness. Results: Extensive time spent at home has adverse effects on all measures, while multi-storey houses perform better than single-story houses with positive correlations with physical activity and spatial novelty. Separate regression models on the variance in depression, as the most salient dependent variable and reliably associated with neurogenesis, reveal that getting out of the house explains 20.5% of the variance in depression symptoms. At the scale of the house, multi-storey houses explain 16.5% of the variance. Both percentages are closer to the effect of loneliness, which we found to explain 26.6% of the variance in depression. Conclusions: The built environment appears to be significantly associated with changes in cognitive function and mental health symptoms associated with neurogenesis. This pilot study shows the equally important effect of physical and social enrichment, offering critically needed insights for neuroarchitecture and brain health research that is interested in public health.