Effects of Histone Modification in Major Depressive Disorder

Wu, Man-Si; Li, Xiaojuan; Liu, Chenyue; Xu, Qiuyue; Huang, Junqing; Gu, Shanqiang; Chen, Jiaxu

doi:10.2174/1570159x19666210922150043

Cited by 29 publications

(6 citation statements)

References 189 publications

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“…In addition to the drugs discussed above, drugs with more specific epigenetic actions are being investigated for the treatment of psychiatric disorders. For instance, HDAC inhibitors are being studied for treating disorders such as MDD [ 78 , 79 ]. The naturally occurring compounds L-methylfolate and S-adenosylmethionine which increase DNA methylation are being studied for treating psychiatric disorders such as MDD [ 80 , 81 ] and SZ [ 81 ].…”

Section: Reversal Of Genome–environment Interactions In the Treatment...mentioning

confidence: 99%

Genome–Environment Interactions and Psychiatric Disorders

Peedicayil

2023

Biomedicines

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Environmental factors are known to interact with the genome by altering epigenetic mechanisms regulating gene expression and contributing to the pathogenesis of psychiatric disorders. This article is a narrative review of how the major environmental factors contribute to the pathogenesis of common psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorder this way. The cited articles were published between 1 January 2000 and 31 December 2022 and were obtained from PubMed and Google Scholar. The search terms used were as follows: gene or genetic; genome; environment; mental or psychiatric disorder; epigenetic; and interaction. The following environmental factors were found to act epigenetically on the genome to influence the pathogenesis of psychiatric disorders: social determinants of mental health, maternal prenatal psychological stress, poverty, migration, urban dwelling, pregnancy and birth complications, alcohol and substance abuse, microbiota, and prenatal and postnatal infections. The article also discusses the ways by which factors such as drugs, psychotherapy, electroconvulsive therapy, and physical exercise act epigenetically to alleviate the symptoms of psychiatric disorders in affected patients. These data will be useful information for clinical psychiatrists and those researching the pathogenesis and treatment of psychiatric disorders.

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Section: Reversal Of Genome–environment Interactions In the Treatment...mentioning

confidence: 99%

Genome–Environment Interactions and Psychiatric Disorders

Peedicayil

2023

Biomedicines

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“…Studies on the direct association between histone phosphorylation and depression are limited. These studies have focused on the stress response and have detected that H3 phosphorylation is increased in the hippocampus and prefrontal cortex of mice and rats, respectively that have been subjected to stress (83). Research on histone ubiquitination and its role in depression is also limited.…”

Section: Epigenetics and Depressionmentioning

confidence: 99%

Biological mechanisms underlying depression, epigenetics and their interplay (Review)

2023

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Depression is a prevalent mood disorder that heavily affects the quality of life of affected individuals. The pathogenesis of depression is relatively complex, with the existing hypotheses focusing on alterations in monoamine signaling, the dysfunction of the hypothalamus-pituitary-adrenal glands axis, and a deregulated immune response. Moreover, the effectiveness of currently used pharmacotherapy, which is mostly based on the monoamine hypothesis, is not satisfactory. The study of epigenetics, i.e., heritable, and stable structural and biochemical alterations of the chromosome that are not associated with DNA sequence alterations, may help to elucidate the molecular mechanisms underlying depression and the response of patients to antidepressants. Epigenetic mechanisms, such as DNA methylation, histone modifications and regulation by non-coding RNAs appear to affect the disease pathogenesis and appear to play a crucial role in the functions of antidepressants. Therefore, research on the influence of epigenetics on depression may prove to be fruitful. The present review aims to accumulate all known information regarding the biological mechanisms underlying depression, epigenetics and the response of patients to antidepressants.

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“…Traditionally researched for their role in deacetylating histones and thereby silencing gene transcription [2,3], some of these enzymes, mainly class II HDACs, deacetylate non-histone proteins, thereby regulating the activity of proteins whose localization or function may depend on posttranslational acetylation [4][5][6][7][8]. Altered HDAC expression has long been linked to carcinogenesis [9], and more recent studies have linked it to depressive episodes [10,11]. Sodium butyrate, which inhibits various HDACs, exerts therapeutic effects in a mouse model of depression [12].…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation

Dai,

Wei,

Huang

et al. 2023

Cell. Mol. Life Sci.

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Major depressive disorder (MDD) is a pervasive and devastating mental disease. Broad spectrum histone deacetylase (HDAC) inhibitors are considered to have potential for the treatment of depressive phenotype in mice. However, due to its non-specific inhibition, it has extensive side effects and can not be used in clinical treatment of MDD. Therefore, finding specific HDAC subtypes that play a major role in the etiology of MDD is the key to develop corresponding specific inhibitors as antidepressants in the future. Copy number variation in HDAC9 gene is thought to be associated with the etiology of some psychiatric disorders. Herein, we found that HDAC9 was highly expressed in the hippocampus of chronic restraint stress (CRS) mouse model of depression. Upregulation of HDAC9 expression in hippocampal neurons of mice induced depression-like phenotypes, including anhedonia, helplessness, decreased dendritic spine density, and neuronal hypoexcitability. Moreover, knockdown or knockout of HDAC9 in hippocampal neurons alleviated depression-like phenotypes caused by chronic restraint stress (CRS) in WT mice. Importantly, using immunoprecipitation–mass spectrometry (IP–MS), we further found that Annexin A2 (ANXA2) was coupled to and deacetylated by HDAC9. This coupling resulted in the inhibition of ubiquitinated ANXA2 degradation and then mediates depression-like behavior. Overall, we discovered a previously unrecognized role for HDAC9 in hippocampal neurons in the pathogenesis of depression, indicating that inhibition of HDAC9 might be a promising clinical strategy for the treatment of depressive disorders.

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Effects of Histone Modification in Major Depressive Disorder

Cited by 29 publications

References 189 publications

Genome–Environment Interactions and Psychiatric Disorders

Genome–Environment Interactions and Psychiatric Disorders

Biological mechanisms underlying depression, epigenetics and their interplay (Review)

Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation

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