Basic pathophysiological mechanisms in affective disorders are discussed. Studies carried out suggest that changes in neurogenesis do not underlie the behavioral changes which lead to helplessness. Since the behavioral changes leading to depressive or anxious behaviors are not correlated with changes in neurogenesis it appears unlikely that a decrease in the rate of neurogenesis is the basis for depression. A modified gene expression resulting in both functional and structural brain changes remains the most consistent hypothesis to explain how affective disorders may occur. An alternative candidate, synaptogenesis, appears as a likely candidate and requires further experimental testing.