State-dependent changes in the expression of DNA methyltransferases in mood disorder patients

• Published in: Journal of psychiatric research 2011-10, Vol.45 (10), p.1295-1300
• Main Authors: Higuchi, Fumihiro, Uchida, Shusaku, Yamagata, Hirotaka, Otsuki, Koji, Hobara, Teruyuki, Abe, Naoko, Shibata, Tomohiko, Watanabe, Yoshifumi
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Affective disorders; Biological and medical sciences; Bipolar depression; Bipolar Disorder - metabolism; Bipolar Disorder - psychology; Bipolar disorders; Depression; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - psychology; Depressive personality disorders; DNA; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA methylation; DNA Methyltransferase 3B; Epigenetics; Female; Gene expression; Gene Expression Regulation; Humans; Leukocyte; Leukocytes - metabolism; Major depression; Male; Medical sciences; Middle Aged; Mood disorders; Pathophysiological aspects; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Real-Time Polymerase Chain Reaction; Recurrence; Regulation; Remission, Spontaneous; RNA, Messenger - metabolism
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2011.04.008

Abstract Aberrant transcriptional regulation may be one of the key components of the pathophysiology of mood disorders. DNA methylation generally acts as an epigenetic gene silencing mechanism and is catalyzed by a group of enzymes known as DNA methyltransferases (DNMTs). Several lines of evidence have suggested aberrant DNA methylation in patients with neuropsychiatric disorders and in animal models for psychiatric disorders. However, the involvement of DNMTs in the pathophysiology of mood disorders is not completely understood. In this study, we aimed to determine whether there are alterations in the expression of DNMTs mRNA in mood disorder patients. We used quantitative real-time PCR to measure the mRNA expression of four DNMT isoforms in the peripheral white blood cells of major depressive disorder (MDD) and bipolar disorder (BPD) patients during a depressive and a remissive episode. We found that the levels of DNMT1 mRNA were significantly decreased in a depressive but not in a remissive state of MDD and BPD. In addition, the levels of DNMT3B mRNA in MDD were significantly increased in a depressive but not in a remissive state. Thus, our data suggest that the altered expression of DNMTs is state dependent and that the aberrant epigenetic gene regulations caused by the altered expression of DNMT1 and DNMT3B may be associated with the pathophysiology of mood disorders.