Modifying Factors of Adult Hippocampal Neurogenesis: A Dorsoventral Perspective in Health and Disease

Adult hippocampal neurogenesis (AHN) is a dynamic process that sustains neural plasticity and contributes to cognition, emotion, and stress resilience. While its functional significance in humans remains debated, growing evidence suggests that AHN plays an important role in health and disease. In this review, we summarize intrinsic and extrinsic factors that modulate AHN, with particular emphasis on hormones, behavior, diet, and their impact along the hippocampal dorsoventral axis, where baseline neurogenesis is higher dorsally, but ventral neurogenesis exhibits greater plasticity and sensitivity to modulatory systems. We highlight how cognitive stimulation, physical activity, and rewarding experiences preferentially enhance dorsal hippocampal neurogenesis, whereas chronic stress and glucocorticoids mainly impair neurogenesis in the ventral hippocampus. Nutritional influences such as caloric restriction, high-fat diets, vitamins, and polyphenols are also considered, with evidence for region-specific effects. We further examine the relevance of AHN alterations in neuropsychiatric diseases, such as major depressive disorder, schizophrenia, Alzheimer’s disease, and addiction, highlighting both common mechanisms and disorder-specific vulnerabilities. Collectively, current findings suggest that AHN serves as a converging pathway connecting lifestyle, neuroendocrine regulation, and psychiatric or neurodegenerative disease. Recognizing the dorsoventral specialization of AHN could refine mechanistic models of brain function and inform the development of targeted and distinct therapeutic strategies for cognitive and affective diseases.