Altered gene expression of histone deacetylases in mood disorder patients.
Chromatin remodeling such as changes in histone acetylation has been suggested to play an important role in the pathophysiology and treatment of mood disorders. In the present study, we investigated whether the expression of histone deacetylase (HDAC) genes are altered in mood disorder patients. We used quantitative real-time PCR to measure the mRNA levels of 11 HDACs (HDAC1-11) in peripheral white blood cells of major depressive disorder (MDD) and bipolar disorder (BPD) patients during depressive and remissive episodes and in the first-degree relatives of BPD patients. In addition, we investigated the effect of antidepressants and mood stabilizers on the mRNA levels of HDACs using mice. In MDD, the expression of HDAC2 and -5 mRNA was increased in a depressive state, but not in a remissive state, compared to controls. In BPD, the expression of HDAC4 mRNA was increased only in a depressive state, and the expression of HDAC6 and -8 was decreased in both depressive and remissive states compared to controls, whereas the first-degree relatives did not show any significant alteration in expression levels. Animal study showed that the expression of HDAC2 and -5 or HDAC4, -6 and -8 mRNAs in the mouse leukocytes were not affected by chronic treatment with antidepressants or mood stabilizers. Our data suggest that aberrant transcriptional regulation caused by the altered expression of HDACs is associated with the pathophysiology of mood disorders.
Hobara
Teruyuki
T
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
Uchida
Shusaku
S
Otsuki
Koji
K
Matsubara
Toshio
T
Funato
Hiromasa
H
Matsuo
Koji
K
Suetsugi
Masatomo
M
Watanabe
Yoshifumi
Y
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002997:Clomipramine / Q000494:pharmacology / Q000627:therapeutic use; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects; D003907:Dexamethasone; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D019964:Mood Disorders / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D012333:RNA, Messenger; D017374:Paroxetine; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006655:Histone Deacetylases; D002997:Clomipramine; D006854:Hydrocortisone