A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings.
Journal of Genetics and Genomics = Yi Chuan Xue Bao
The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders.
Over the last several years proteins involved in base excision repair (BER) have been implicated in active DNA demethylation. We review the literature supporting BER as a means of active DNA demethylation, and explain how the various components function and cooperate to remove the potentially most enduring means of epigenetic gene regulation. Recent evidence indicates that the same pathways implicated during periods of widespread DNA demethylation, such as the erasure of methyl marks in the paternal pronucleus soon after fertilization, are operational in post-mitotic neurons.
INTRODUCTION: Suicide is a major health problem, and depression is a major psychiatric cause of suicide. Suicide is influenced by the multifactorial interaction of many risk factors. Therefore, epigenetic research may lead to understandings that are applicable to suicide. This study investigated whether epigenetic changes are associated with suicidal behavior and evaluated the treatment outcome of suicidal ideation in depressive patients. METHODS: In 108 patients with major depression, the promoter methylation of the gene encoding brain-derived neurotrophic factor (BDNF) was measured.
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry
OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been considered a risk factor for suicidal behavior in adult populations. BDNF secretion is influenced by epigenetic (DNA promoter methylation) and genetic (val66met polymorphism) profiles. We investigated the independent and interactive effects of BDNF methylation status and val66met polymorphisms on late-life suicidal ideation. METHODS: In total, 732 Korean community residents aged 65+ years were evaluated; of 639 without suicidal ideation, 579 (90.6%) were followed up 2 years later.
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics
Brain-derived neurotrophic factor (BDNF) is involved in the survival, development, and synaptic plasticity of neurons. BDNF is believed to be associated with the pathophysiology of psychiatric disorders. Several studies have suggested the relevance of DNA methylation in its promoter region with depression. Here, we report different methylation statuses in groups with different depressive scores or undergoing different levels of job-stress.
The BDNF is required for the development and proper function of the central nervous system, where it is involved in a variety of neural and molecular events relevant to cognition, learning, and memory processes. Although only a functional mature protein is synthesized, the human BDNF gene possesses an extensive structural complexity, including the presence of multiple promoters, splicing events, and 3¥UTR poly-adenylation sites, resulting in an intricate transcriptional regulation and numerous messengers RNA. Recent data support specific cellular roles of these transcripts.
Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders.
Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are currently being investigated in animal models and clinical studies. However, very little is currently known about the mechanisms that deregulate BDNF gene expression in these disorders. The BDNF gene structure and tissue expression pattern is complex, controlled in humans by 9 different gene promoters.
Proceedings of the National Academy of Sciences of the United States of America
Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue.