Association between DNA Methylation Levels in Brain Tissue and Late-Life Depression in Community-Based Participants

Hüls, Anke; Robins, Chloe; Conneely, Karen N.; Jager, Philip L. De; Bennett, David A.; Epstein, Michael P.; Wingo, Thomas S.; Wingo, Aliza P.

doi:10.1101/2020.04.21.20074021

Cited by 3 publications

(2 citation statements)

References 51 publications

(76 reference statements)

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“…In depression, a discordant monozygotic twin study based on peripheral blood, found 39 DMRs associated to a lifetime history of MDD, which were significantly enriched in biological pathways associated to cytokine secretion (Zhu et al, 2020). Another EWAS on post-mortem brain of people with late-MDD (Hüls et al, 2020), found altered DNAm in the YOD1 locus, which is dysregulated in depression (Howren, Lamkin, & Suls, 2009) and its implicated in the regulation of inflammatory processes (Schimmack et al, 2017).…”

Section: Evidence Of Epigenetic Processes In Major Transdiagnostic Pa...mentioning

confidence: 99%

Can epigenetics shine a light on the biological pathways underlying major mental disorders?

et al. 2022

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A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the development of novel pharmacological treatments. Epigenetic mechanisms have emerged as mediators of environmental and genetic risk factors which might play a role in disease onset, including childhood adversity (CA) and cannabis use (CU). Particularly, human research exploring DNA methylation has provided new and promising insights into the role of biological pathways implicated in the aetio-pathogenesis of psychiatric conditions, including: monoaminergic (Serotonin and Dopamine), GABAergic, glutamatergic, neurogenesis, inflammatory and immune response and oxidative stress. While these epigenetic changes have been often studied as disease-specific, similarly to the investigation of environmental risk factors, they are often transdiagnostic. Therefore, we aim to review the existing literature on DNA methylation from human studies of psychiatric diseases (i) to identify epigenetic modifications mapping onto biological pathways either transdiagnostically or specifically related to psychiatric diseases such as Eating Disorders, Post-traumatic Stress Disorder, Bipolar and Psychotic Disorder, Depression, Autism Spectrum Disorder and Anxiety Disorder, and (ii) to investigate a convergence between some of these epigenetic modifications and the exposure to known risk factors for psychiatric disorders such as CA and CU, as well as to other epigenetic confounders in psychiatry research.

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Section: Evidence Of Epigenetic Processes In Major Transdiagnostic Pa...mentioning

confidence: 99%

Can epigenetics shine a light on the biological pathways underlying major mental disorders?

et al. 2022

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“…We further assessed over-representation for differentially expressed genes (DEGs) and genes proximal to differentially methylated CpG islands (DMGs) in the dorsolateral prefrontal cortex of patients with SCZ 21,22 and patients with MDD 7,23,24 and for loss of function intolerant genes (LoF) 25 .…”

Section: Biological and Functional Enrichment Analysis Of Sda Componentsmentioning

confidence: 99%

Prefrontal Interneuron Genes Underlie Neurobiological Processes Shared Between Psychiatric Disorders

Sportelli

Nagy²,

Weinberger³

et al. 2022

European Neuropsychopharmacology

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Prefrontal interneuron genes underlie neurobiological processes shared between psychiatric disorders

Pergola

Sportelli²,

Nagy³

et al. 2022

Preprint

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Previous reports on brain co-expression networks, mostly applied to tissue homogenates, have utilized cluster-based strategies for assigning genes to a unique co-expression cluster. This feature is incompatible with the diversity of cell populations and cellular components involved. Single-cell RNA-sequencing provides a finer-grained resolution than bulk tissue when interrogating brain cell types, dynamic states, and functional processes. We uncovered co-expression patterns across different brain cell types by applying tensor decomposition to single-nucleus transcriptomes from the prefrontal cortex of male patients with depression who died by suicide. We identified a gene set differentially co-expressed in inhibitory neurons between patients and controls and enriched for genes associated with major depression and schizophrenia.

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Association between DNA Methylation Levels in Brain Tissue and Late-Life Depression in Community-Based Participants

Cited by 3 publications

References 51 publications

Can epigenetics shine a light on the biological pathways underlying major mental disorders?

Can epigenetics shine a light on the biological pathways underlying major mental disorders?

Prefrontal Interneuron Genes Underlie Neurobiological Processes Shared Between Psychiatric Disorders

Prefrontal interneuron genes underlie neurobiological processes shared between psychiatric disorders

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