Pathological or preventative? Amyloid-β as an effector of innate immunity.

Rapid, unprecedented global urbanization has precipitated a profound public health crisis, characterized by a surging prevalence of mental health disorders. According to the World Health Organization [, ], nearly one billion people worldwide live with a mental disorder, with depression and anxiety escalating by over 25% in the wake of recent global socio-environmental stressors. This crisis imposes a staggering economic burden, projected to cost the global economy USD 6 trillion annually by 2030 due to lost productivity and healthcare expenditures []. From an environmental and evolutionary standpoint, this phenomenon is deeply rooted in the “Evolutionary Mismatch Hypothesis” (EMH). EMH [, ] posits that human biological and psychological adaptations were forged over millions of years within EEA (Environment of Evolutionary Adaptedness) conditions—characterized by high-biodiversity, natural landscapes, and low-density social structures. The abrupt transition to hyper-densified, artificial, and sensorially overloaded urban environments represents a profound structural mismatch, overtaxing cognitive faculties and chronically activating sympathetic stress responses []. While environmental psychology frameworks like Attention Restoration Theory (ART) and Stress Reduction Theory (SRT) have long sought to explain the therapeutic potential of natural elements in mitigating this mismatch, their operationalization within contemporary urban planning remains constrained by persistent empirical boundaries. Historically, environmental psychology has relied on two cornerstone theories to explain the health-promoting effects of natural environments: Stress Reduction Theory (SRT), proposed by Roger Ulrich [, ], and Attention Restoration Theory (ART), developed by Kaplan and Kaplan [, ]. Grounded in psycho-evolutionary theory, SRT posits that human preference for natural environments is a genetically encoded survival instinct. Ulrich argues that encounters with natural landscapes possessing “survival-advantageous” features—such as water bodies, vegetation, and open vistas—rapidly trigger positive affective responses in the limbic system. This response is pre-cognitive, automatic, and directly downregulates sympathetic nervous system arousal.