Altered gene expression of histone deacetylases in mood disorder patients
Abstract
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.
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Upon remission, HDAC2 and HDAC5 levels normalized to those of healthy controls.
“Interestingly, upon remission, the levels normalized to those of healthy controls”
From Epigenetics and depression (2019) · cites this paper as [25]
HDAC levels have potential to be used as a biomarker for disease monitoring.
“highlighting the potential of HDAC levels to be used as a biomarker for disease monitoring.”
From Epigenetics and depression (2019) · cites this paper as [25]
Elevated HDAC2 and HDAC5 levels were found in patients experiencing an acute depressive episode.
“One study found elevated HDAC2 and HDAC5 levels in patients experiencing an acute depressive episode.”
From Epigenetics and depression (2019) · cites this paper as [25]
Differential brain expression of HDACs was found in postmortem tissue in MDD.
“differential brain expression of HDACs was found in the postmortem in MDD.130,159”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [159]
Expression of HDAC2 and HDAC5 was higher during a depressive state compared with remission in peripheral white blood cells of patients diagnosed with MDD and bipolar disorder.
“Expression of HDAC2 and HDAC5 was higher during a depressive state, compared with remission, in peripheral white blood cells of patients diagnosed with MDD and bipolar disorder (BPD).159”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [159]
Expression of HDAC6 and HDAC8 was lower regardless of mood states compared with controls in BPD, while HDAC4 expression was higher only in a depressive state.
“The expression of HDAC6 and HDAC8 was lower regardless of mood states compared with controls in BPD, while the HDAC4 expression was higher only in a depressive state.159”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [159]
Higher levels of HDAC4 and HDAC5 were found in depressed patients.
“Higher levels of HDAC4 and HDAC5 were found in depressed patients.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [81]
Increased HDAC2 expression and reduced GDNF expression have been shown in patients with major depressive disorder.
“Further, some reports have shown increased HDAC2 expression and reduced GDNF expression in patients with MDD”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [81]
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- Authors
- Hobara, T., Uchida, S., Otsuki, K., Matsubara, T., Funato, H., Matsuo, K., Suetsugi, M., & Watanabe, Y.
- Affiliations
- Yamaguchi University (JP)
- Corresponding author
- Watanabe, Yoshifumi
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 44
- Issue
- 5
- Pages
- 263-270
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2148160168
- Cited by
- 185
- References
- 57
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 17 · 2020: 18 · 2019: 11 · 2018: 10 · 2017: 16 · 2016: 10 · 2015: 15 · 2014: 9 · 2013: 16 · 2012: 9
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- histone deacetylase, mood disorders, major depressive disorder, bipolar disorder, HDAC2, HDAC5, HDAC4, HDAC6, HDAC8, gene expression, peripheral blood leukocytes, leukocytes, histone acetylation, chromatin remodeling, antidepressants, mood stabilizers, first-degree relatives
- MeSH terms
- Animals, Antidepressive Agents, Clomipramine, Corticotropin-Releasing Hormone, Dexamethasone, Disease Models, Animal, Female, Gene Expression Regulation, Histone Deacetylases, Humans, Hydrocortisone, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Middle Aged, RNA, Messenger, Swimming, Paroxetine, Mood Disorders, Mice
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