engleski

Genotype-controlled analysis of plasma dopamine-beta-hydroxylase activity in posttraumatic stress disorder

Introduction: Dopamine beta-hydroxylase (DBH) is the enzyme that converts dopamine to norepinephrine. Altered plasma DBH activity has been reported in various psychiatric disorders. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene could be related to etiology of posttraumatic stress disorder (PTSD), given the well-documented changes in the catecholamine-mediated neurotransmission that occurs in this disorder. The aim of the present study was to investigate whether the functional polymorphism DBH-1021C/T (rs1611115) and plasma DBH activity were associated with PTSD, or with psychotic and non-psychotic subtypes of PTSD. Methods: Plasma DBH activity and DBH-1021C/T polymorphisms were determined in 329 male subjects: 162 healthy controls, 133 combat veterans with current and chronic PTSD (subdivided further into two subgroups according to the presence or absence of psychotic features) and in 34 veterans without chronic PTSD. PTSD diagnosis was done using the Structured Clinical Interview (SCID) for DSM-IV. Plasma DBH activity was determined by a photometric method and genotyping by standard RFLP technique. Results: There was a significant decrease in plasma DBH activity among war veterans with PTSD, regardless of the presence of psychotic symptoms, as compared to enzyme activity in war veterans without PTSD and healthy controls. No significant differences were detected in genotype or allele frequencies between healthy controls, war veterans with and without PTSD. War veterans with PTSD carrying CC genotype had significantly lower plasma DBH activity compared to all other subjects with the CC genotype. There was no relationship between smoking status, plasma DBH activity and polymorphisms within DBH gene. Conclusion. Since both groups of war veterans were exposed to the same trauma, it is possible that a pre-existing trait difference in regulation of noradrenergic function contributed to a differential vulnerability to develop PTSD, or that the regulation of DBH expression was different in response to trauma. The results suggest that genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker of the response to trauma, and that further studies of DBH and other loci related to dopamine and noradreneline in PTSD are warranted.

genotype-controlled measurement; plasma DBH activity; potential biological markers; response to trauma

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