Depression and Gene-Environment Interaction

Abstract

Major depressive disorder (MDD) is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. MDD is also a complex and heterogeneous disorder, at etiological, phenotypical, and biological levels. The gene or series of genes, which cause MDD, have so far not been identified. However, certain genetic variations, called polymorphisms, may increase the risk of MDD in a susceptible person. In addition, environmental stress also is a common precipitating factor of MDD. Various stressful life-experiences-prenatal stress, aversive early life experiences, ongoing or recent psychosocial stress-are important en-vironmental factors contributing to the development of MDD. Nevertheless, not all persons ex-posed to these stresses become depressed. Environmental stress interacts with a person’s ge-netic makeup to influence his or her risk for developing MDD. It is the combination of genes, early life stress, and ongoing stress, which may ultimately determine an individual’s responsiveness to stress and vulnerability to MDD. Consequently, the gene and environment interactions may impact multiple neurobiological systems implicated in MDD. The gene-environment interaction in the pa-thophysiology of MDD leads to advances in personalized medicine by means of genotyping for inter-individual variability in drug action and metabolism. Such concept may explain why some subjects become depressed while others remain unaffected.