Lecture Overview

Despite remarkable advances in biological psychiatry in recent years, clinical practice in psychiatry continues to face significant challenges. Misdiagnosis remains common due to the lack of clinically useful biomarkers, and treatment options are still limited to drugs based on the classical monoamine hypothesis. Therefore, there is an urgent need to develop new diagnostic and therapeutic approaches for psychiatric disorders based on pathophysiological hypotheses that go beyond the monoamine hypothesis.

Among hypotheses that transcend the monoamine framework, the most prominent is the neurogenesis hypothesis. This hypothesis was established between the late 1980s and early 2000s, when it was demonstrated that adult neurogenesis occurs in the hippocampal dentate gyrus, that glucocorticoids mediating stress suppress adult hippocampal neurogenesis, and that antidepressants, mood stabilizers, and electrical stimulation can enhance it. Suppression of hippocampal neurogenesis reduces the efficacy of antidepressants, which has led many researchers to accept the neurogenesis hypothesis. Since then, an extensive body of basic research has accumulated.

However, a fundamental problem remains: neurogenesis cannot be directly detected in living humans, so it is still unknown whether hippocampal neurogenesis is actually reduced in patients with psychiatric disorders. Furthermore, no novel diagnostic methods or treatments based on this hypothesis have yet been developed. Thus, although the neurogenesis hypothesis is strongly supported by basic research, it still faces multiple unresolved challenges.

In this seminar, I will first provide an overview of adult hippocampal neurogenesis, followed by a review of key studies supporting the neurogenesis hypothesis and the mechanisms of action of therapeutic drugs derived from it. I will then highlight the limitations of the neurogenesis hypothesis and discuss potential strategies to address these challenges.