6533b82efe1ef96bd129449a

RESEARCH PRODUCT

Association study of affective disorders with genetic polymorphisms of monoamine oxidases

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Introduction: Monoamine oxidases (MAO) catalyze the oxidative deamination of monoamines like norepinephrine, serotonin and dopamine. The existing MAOs (A and B) have distinct although partially overlapping biological functions and distributions in the brain. MAO A is mainly expressed in catecholaminergic neurons. Thirty-fold differences in enzyme activity of MAO A can be found in cultured cells from different individuals suggesting a genetic determination of enzyme activity. Indeed, a point mutation in the coding region of the gene which creates a restriction site for Fnu4HI alters the activity. Moreover, the pharmacological inhibition of monoamine oxidase A activity is one of the most effective treatments of depressive symptoms. MAO B is expressed at highest levels in astrocytes and serotonergic neurons. Fitly-fold differences in the activity of MAO-B have also been observed, although it is not known whether the polymorphism investigated in this study is associated with differences in the activity levels. Interestingly, MAO-B knock out mice show an increased stress reactivity which is known to be a risk factor for the development of major depressive symptoms. In this study, we hypothesized that variations in the above mentioned genes are associated with affective disorders. Methods: We investigated psychiatric patients who were treated for acute major depressive disorders according to DSM-IV diagnostic criteria and showed a score of at least 18 points on the HAM-D 17 item version. The selected patients were all Caucasians, 27 male and 78 female and were aged 1865 years. Exclusion criteria for all groups included any serious medical condition, mood disorders due to a general medical condition or substance abuse, dementia, and also schizophrenia and related psychotic disorders. Control subjects were 18-65 year old Caucasians. Their mental health was investigated by standardized diagnostic interviews. Subsequently, we included 139 males and 126 females without relevant somatic and with no psychiatric disorder. Afier written informed consent had been obtained from all subjects blood samples were collected and the distribution of genetic polymorphisms in the MAO genes was examined. Chi-square tests were performed to compare allele and genotype frequencies. Results and Discussion: There was no association of the polymorphisms in the MAO genes with affective disorders. MAO A: females: p = 0.524 for allele and p = 0.477 for genotype frequencies; males: p = 0.497 for allele and p = 0.908 for genotype frequencies. MAO B: females: p = 0.186 for allele and p = 0.3 11 for genotype frequencies; males: p = 0.470 for allele and p = 0.910 for genotype frequencies. These results do not support the hypothesis that genetic variations in the MAO A or MAO B genes contribute to the genetic vulnerability for unipolar depression.