Neuroepigenetics of Neuropsychiatric Disease – Hope, Success and Obstacles for Translational Findings and Applications

Graphical abstract shows mechanisms for development of neuropsychiatric diseases.

Editorial

01 April 2022

Editorial: Neuroepigenetics of Neuropsychiatric Disease—Hope, Success and Obstacles for Translational Findings and Applications

Yan Jiang

Julia M. Schulze-Hentrich

and

Mira Jakovcevski

2,628 views

2 citations

Editors

Mira Jakovcevski

Max Planck Institute of Psychiatry (MPI)

Julia Maria Schulze-Hentrich

Saarland University

Yan Jiang

Fudan University

Impact

Review

13 May 2021

Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Jiaqi Zhou

, 7 more and

Chao Chen

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.

10,056 views

32 citations

Review

07 December 2020

The Way to a Human’s Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder

Janine Aly

and

Olivia Engmann

Globally, more than 250 million people are affected by depression (major depressive disorder; MDD), a serious and debilitating mental disorder. Currently available treatment options can have substantial side effects and take weeks to be fully effective. Therefore, it is important to find safe alternatives, which act more rapidly and in a larger number of patients. While much research on MDD focuses on chronic stress as a main risk factor, we here make a point of exploring dietary factors as a somewhat overlooked, yet highly promising approach towards novel antidepressant pathways. Deficiencies in various groups of nutrients often occur in patients with mental disorders. These include vitamins, especially members of the B-complex (B6, B9, B12). Moreover, an imbalance of fatty acids, such as omega-3 and omega-6, or an insufficient supply with minerals, including magnesium and zinc, are related to MDD. While some of them are relevant for the synthesis of monoamines, others play a crucial role in inflammation, neuroprotection and the synthesis of growth factors. Evidence suggests that when deficiencies return to normal, changes in mood and behavior can be, at least in some cases, achieved. Furthermore, supplementation with dietary factors (so called “nutraceuticals”) may improve MDD symptoms even in the absence of a deficiency. Non-vital dietary factors may affect MDD symptoms as well. For instance, the most commonly consumed psychostimulant caffeine may improve behavioral and molecular markers of MDD. The molecular structure of most dietary factors is well known. Hence, dietary factors may provide important molecular tools to study and potentially help treat MDD symptoms. Within this review, we will discuss the role of dietary factors in MDD risk and symptomology, and critically discuss how they might serve as auxiliary treatments or preventative options for MDD.

10,684 views

24 citations

Analysis of apoptosis and proliferation of oligodendroglial lineage cells after Met treatment. (A) Representative images showing immunofluorescence staining of TUNEL and Olig2 in the frontal white matter of mice. White arrows indicate representative TUNEL and Olig2 duoble-labling cells. The left bar graph shows the quantification of density of TUNEL positive cells (n = 5 for each group). The right bar graph shows the density of Olig2/TUNEL double-labeling cells (n = 5 for each group). (B) Representative images showing immunofluorescence staining of Ki67 and Olig2 in the frontal white matter of mice. The white dashed line indicates the edge of frontal white matter. The left bar graph shows the quantification of density of Olig2 positive cells (n = 5 for each group). The right bar graph shows the percentage of Olig2/Ki67 double-labeling cells to Olig2 positive cells (n = 5 for each group). Scale bars = 50 μm. The data are expressed as the mean ± SEM. *P < 0.05; **P < 0.01; ns, no significant difference.

Original Research

20 April 2021

DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice

Xianjun Chen

, 5 more and

Lan Xiao

3,566 views

7 citations

Review

12 November 2020

Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders

Zhilian Jia

and

Qiang Wu

The clustered protocadherins (cPcdhs) are a subfamily of type I single-pass transmembrane cell adhesion molecules predominantly expressed in the brain. Their stochastic and combinatorial expression patterns encode highly diverse neural identity codes which are central for neuronal self-avoidance and non-self discrimination in brain circuit formation. In this review, we first briefly outline mechanisms for generating a tremendous diversity of cPcdh cell-surface assemblies. We then summarize the biological functions of cPcdhs in a wide variety of neurodevelopmental processes, such as neuronal migration and survival, dendritic arborization and self-avoidance, axonal tiling and even spacing, and synaptogenesis. We focus on genetic, epigenetic, and 3D genomic dysregulations of cPcdhs that are associated with various neuropsychiatric and neurodevelopmental diseases. A deeper understanding of regulatory mechanisms and physiological functions of cPcdhs should provide significant insights into the pathogenesis of mental disorders and facilitate development of novel diagnostic and therapeutic strategies.

9,137 views

38 citations