Association of genetic polymorphisms with drug-response and personality in mood disorders

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Lifetime prevalence of mood disorders is estimated about 15% and mood disorders cause a serious social loss and a high suicide rate. There are many treatment-resistant cases with mood disorders although the treatment by antidepressants and mood stabilizers has been established. The pathophysiology of this disorders has not yet unknown, thus the elucidation of the pathophysiology is required to establish the prevention and treatment of this condition. According to the clinical genetic studies, such as the family study, the twin study, and the adopted study, genetic factors are hypothesized to participate in the etiology of mood disorders. In addition, abnormal monoamines in patients with mood disorders and monoaminergic mechanisms of psychotropic drugs suggest that abnormality of monoamines participates in the pathophysiology of mood disorders. These two points mentioned above lead to the monoaminergic genetic studies of mood disorders. No reproducible result, however, has acquired. One … More of the reasons for the obstacle is that mood disorders are etiologically heterogeneous disorders. Therefore, we have to grasp the family history, the response to psychotropic drugs, the personality, the breeding experience and the clinical information in order to elucidate the pathophysiology. In addition, by progress of molecular biology, we can search for monoaminergic molecular genetic mechanisms that is used to be impossible. Thus, we started to examine the monoaminergic molecular genetic background in patients with mood disorders after we obtained their drug-response, other biological data, their breeding experience, personality and the clinical features.We examined the personality using the TC1 in depression. As a result, the severity of depression showed the positive correlation with Harm Avoidance, and the negative correlation with Self-Directedness and Cooperativeness. Furthermore, good responders became close to normal values after an antidepressant treatment, but bad responders did not change. On the other hand, on the breeding experience using PBI, patients with depression and OCD showed a low caring of parents and a high protection of a mother. In addition, patients with atopic dermatitis had high Harm Avoidance with TCI and no characteristics with PBI.On the other hand, according to the molecular genetic study of seasonal affective disorder, the 5HTT polymorphism had the association with the disease, but the 5-HT1a, 1b, 1d, 2a, 2c do not.We are going to continue the molecular genetic research to obtain a marker for the drug response and open the road to the development of a new drug. Furthermore, we are carrying out researches to aim at goals as follows. 1) Developing a tool for early discovery of depression. 2) Frequency of mood disorders and an environment factor in laborers and patient with general medical conditions. 3) Effectiveness of cognitive behavior therapy for depression. Less