Involvement of genetic and environmental factors in the onset of depression.
First, this article provides a brief overview of the previous hypotheses regarding depression and then focuses on involvement of genetic and environmental factors in development of depression. According to epidemiological research, 30~40% of occurrences of bipolar disorder involve a genetic factor. Therefore, environmental factors play a more important role in development of depression. Resilience and resistance to stress are common; therefore, although a certain extent of stress might be received during the embryonic or perinatal period, having a genetic predisposition to mental disorders does not imply that a mental disorder will develop. However, having a genetic predisposition to disorders does weaken resistance to stresses received during puberty, and without the ability to recover, a mental disorder is triggered. The importance of epigenetics in maintaining normal development and biology is reflected by the observation that development of many diseases occurs when the wrong type of epigenetic marks are introduced or are added at the wrong time or in the wrong place. Involvement of genetic and environmental factors in the onset of depression was investigated in relation to epigenetics. When mice with the disrupted in schizophrenia 1 (DISC1) abnormal gene received isolated rearing stress, depression-like abnormal behaviors and decreased gene expression of tyrosine hydroxylase in the frontal cortex by epigenetical suppression via DNA methylation were observed. Decrease of dopamine in the frontal cortex triggers behavioral disorders. Administration of a glucocorticoid receptor antagonist resulted in full recovery from neurological and behavioral disorders. These results suggest a new therapeutic approach to depression.
Department of Regional Pharmaceutical Care and Sciences, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan. ; NPO, Japanese Drug Organization of Appropriate Use and Research, Nagoya 468-8503, Japan.
Toshitaka
T
Nabeshima
Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
Hyoung-Chun
HC
Kim
depression; environmental factors; epigenetics; genetic factors; glucocorticoide