Gene silencing: a possible molecular mechanism in remission of affective disorder.
Based upon a case report, the hypothesis is proposed that a virus infection could be responsible for remission of affective disease by causing gene silencing. A farmer of 59 had been suffering from a therapy resistant depressive episode over many months. His depressive illness seemed primarily biogenetically determined. Because of acute suicidality clinical treatment and observation became necessary. After six weeks of unsuccessful psychiatric treatment the patient caught a severe virus infection causing pneumonia and myocarditis. The physical treatment showed up to be difficult, but finally managed to cope with the virus infection. Remarkably, parallel to the decrease of physical symptoms also the mood was markedly elevated towards a full remission. At that time the patient was no longer under antidepressant medication. Many viruses have a genetic blueprint made from RNA, rather than DNA. When they infect a cell, double-stranded copies (double-stranded RNA, dsRNA) of their genetic material are produced. In response, the RNA interference (RNAi) pathway of the infected cell is activated. The enzyme Dicer first chops viral dsRNA into small segments of 21-25 basepairs in length, termed short interfering RNAs (siRNAs) and these siRNAs are used to identify intact viral RNA and to mark it for destruction. When an endogenous gene is activated, its sequence is read to produce messenger RNA (mRNA), which contains the information necessary to produce a particular protein, and improper expression of an endogenous gene could cause affective disorder in a patient. Therefore one would expect that if such a patient were infected by a virus that contained a sequence similar to the improperly expressed endogenous gene, the patient's anti-viral response would inadvertently reduce expression of the gene causing affective disorder. If mutations in genes responsible for affective disorders are identified and they turn out to cause over-expression of a particular gene, gene silencing could be an alternative therapeutic tool, especially for therapy-resistant severe depression. The therapy could involve introducing dsRNA either as synthetic RNA, or by infecting the patient with a recombinant virus containing sequence from the gene whose expression must be reduced.
Mitterauer
B
B
Institute of Forensic Neuropsychiatry and Gotthard Günther Archives, University of Salzburg, Ignaz-Harrer Strasse 79, A-5020 Salzburg, Austria. bernhard.mitterauer@sbg.ac.at
D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008962:Models, Theoretical; D019964:Mood Disorders / Q000235:genetics* / Q000628:therapy*; D034622:RNA Interference; D012074:Remission Induction