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Huth et al.(1) claim that our finding of lower depression rates in larger US cities (2) is “unwarranted.” Their argument is based on an oversight of our fundamental assumption articulating rates of depression to city size: that cities are socioeconomic networks mediated by built environments. Problematically, their analysis is based on a flawed definition of city boundaries. Here, we address each of these points. First, the issue of functional city definitions: The fundamental insight of urban science (3) is that cities are spatially aggregated socioeconomic networks with properties self-consistently shaped by their built infrastructure. Consequently, meaningful spatial city boundaries must capture—in a single unit of analysis—where people live, socialize, and work. In the United States, the well-tested definition that fits these criteria is the metropolitan statistical area (MSA) as delineated by the US Office of Management and …