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Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (5 January 2021) | Viewed by 42239

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Special Issue Editors

Prof. Dr. Piotr Galecki

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Guest Editor

Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland
Interests: clinical psychiatry; neuroimmunology; epigenetics; depression
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Kuan-Pin Su

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Guest Editor

Department of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
Interests: immunopsychiatry; nutritional psychiatry; depression; omega-3 fatty acids; translational medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Depressive disorders are one of the most common mental disorders worldwide, with more than 264 million people affected. They are a leading cause of disability. Despite their high prevalence, the etiopathogenesis of depressive disorders is not yet fully understood. The aim of recent studies in the field of psychiatry is to seek consistent theory that would exhaustively explain the aetiology of depression. Neuroimmunology, epigenetics, and their correlations seem to play an important role in this matter.

We would like to invite experts from all over the world to participate in our common project, a Special Issue of the Journal of Personalized Medicine, titled Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders, in which we would like to focus on the biological background of depressive disorders. Nowadays, when one third of the patients suffer from treatment resistant depression, seeking for new therapeutic targets is especially important. Since depression also has a significant impact on socioeconomics, scientists are also seeking methods of its primary prevention.

Original research papers, brief scientific reports, as well as review papers, regarding the given topic, will be considered for publication in this Special Issue ‘’Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders’’.

Prof. Dr. Piotr Galecki
Prof. Dr. Kuan-Pin Su
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Depression
Major depressive disorder
Neuroimmunology
Epigenetics
Prevention

Published Papers (11 papers)

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Editorial

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2 pages, 177 KiB

Open AccessEditorial

Neuroimmunology and (Epi)Genetics in Depressive Disorders

by Piotr Gałecki, Katarzyna Bliźniewska-Kowalska, Michael Maes and Kuan-Pin Su

J. Pers. Med. 2021, 11(7), 670; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11070670 - 16 Jul 2021

Cited by 2 | Viewed by 1525

Abstract

Depression causes individual suffering, loss of productivity, increased health care costs and high suicide risk [...] Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

Research

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12 pages, 1181 KiB

Open AccessArticle

Is NRXN1 Gene Expression an Important Marker of Treatment of Depressive Disorders? A Pilot Study

by Aleksandra Skiba, Monika Talarowska, Janusz Szemraj and Piotr Gałecki

J. Pers. Med. 2021, 11(7), 637; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11070637 - 06 Jul 2021

Cited by 2 | Viewed by 2608

Abstract

Aim: Due to the fact that NRXN1 is associated with neurodevelopmental disorders, the aim of this study was to investigate the role of the NRXN1 gene in the etiology and epigenetics of depression by comparison of NRXN1 mRNA expression and NRXN1 protein level expression in patients suffering from depression versus healthy controls, as well as to search for clinical variables related to expression of the analyzed gene. Material and Methods: A total of 180 people aged 19–64 qualified for the study. The experimental group consisted of 97 people who were psychiatrically hospitalized, diagnosed with recurrent depressive disorders (F33) or who met the diagnostic criteria of a depressive episode (F32) according to ICD-10. The control group included 83 healthy people who volunteered to participate in the study. A sample of peripheral blood was obtained from people who were positively qualified to participate in the study—twice in the experimental group and once in the control group for genetic testing. Sociodemographic variables and data on the course of the disorder were also gathered. Patients were examined on study entry and at the end of the hospitalization with the Hamilton Depression Scale. Obtained data were analyzed statistically. The study was approved by the University’s Bioethics Committee. Results: The gene expression of NRXN1 at both mRNA and protein level significantly differs and it is lower in the experimental group compared to expression in healthy people. The difference in gene expression of NRXN1 at both the mRNA and protein levels between the first and second measurement in the experimental group is also significant. The result demonstrates a higher expression level in the first measurement and lower expression level in the second measurement when reported depression symptoms are less severe. Conclusions: Results concerning expression of NRXN1 may play an important role in further researches about the etiopathogenesis of depressive disorders such as looking for depression biomarkers and identifying evidence which may be relevant to personalize treatment for depression. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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11 pages, 1639 KiB

Open AccessFeature PaperArticle

Maternal Separation Followed by Chronic Mild Stress in Adulthood Is Associated with Concerted Epigenetic Regulation of AP-1 Complex Genes

by Lene Lundgaard Donovan, Kim Henningsen, Anne Flou Kristensen, Ove Wiborg, John Dirk Nieland and Jacek Lichota

J. Pers. Med. 2021, 11(3), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11030209 - 16 Mar 2021

Cited by 5 | Viewed by 2188

Abstract

Depression is one of the most prevalent mental diseases worldwide. Patients with psychiatric diseases often have a history of childhood neglect, indicating that early-life experiences predispose to psychiatric diseases in adulthood. Two strong models were used in the present study: the maternal separation/early deprivation model (MS) and the chronic mild stress model (CMS). In both models, we found changes in the expression of a number of genes such as Creb and Npy. Strikingly, there was a clear regulation of expression of four genes involved in the AP-1 complex: c-Fos, c-Jun, FosB, and Jun-B. Interestingly, different expression levels were observed depending on the model, whereas the combination of the models resulted in a normal level of gene expression. The effects of MS and CMS on gene expression were associated with distinct histone methylation/acetylation patterns of all four genes. The epigenetic changes, like gene expression, were also dependent on the specific stressor or their combination. The obtained results suggest that single life events leave a mark on gene expression and the epigenetic signature of gene promoters, but a combination of different stressors at different life stages can further change gene expression through epigenetic factors, possibly causing the long-lasting adverse effects of stress. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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10 pages, 278 KiB

Open AccessArticle

Predictive Genetic Variations in the Kynurenine Pathway for Interferon-α-Induced Depression in Patients with Hepatitis C Viral Infection

by Szu-Wei Cheng, Jing-Xing Li, Daniel Tzu-Li Chen, Yu-Chuan Chien, Jane Pei-Chen Chang, Shih-Yi Huang, Piotr Galecki and Kuan-Pin Su

J. Pers. Med. 2021, 11(3), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11030192 - 11 Mar 2021

Cited by 4 | Viewed by 1996

Abstract

Importance: The high incidence of major depressive episodes during interferon-α (IFN-α) therapy is considered the most powerful supportive evidence for the inflammation theory of depression. As the kynurenine pathway plays an important role connecting inflammation and depression, it is plausible to investigate this pathway for predictive genetic markers for IFN-α-induced depression. Methods: In this prospective case-control study, we assessed 291 patients with chronic hepatitis C viral infection taking IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes in the kynurenine pathway. Our case group contained patients who developed IFN-α-induced depression during the treatment, and others were defined as the control group. Genomic DNA was extracted from leukocytes in the peripheral blood and analyzed by Affymetrix TWB array. We first tested allelic, dominant, and recessive models on each of our SNPs using Fisher’s exact test. We then conducted 5000 gene-wide max(T) permutations based on the best model of each SNP to provide strong gene-wide family-wise error rate control. Finally, we preformed logistic regression for the significant SNPs acquired in previous procedures, with sex and education level as covariates to build predictive models. Additional haplotype analyses were conducted with Haploview 4.2 to investigate the combining effect of multiple significant SNPs within a gene. Results: With sex and education level as covariates, rs8082252 (p = 0.0015, odds ratio = 2.716), rs8082142 (p = 0.0031, odds ratio = 2.499) in arylformamidase (AFMID), and rs12477181 (p = 0.0004, odds ratio = 0.3478) in kynureninase (KYNU) were significant in logistic regression models with dominant modes of inheritance. Haplotype analyses showed the two significant SNPs in AFMID to be in the same haploblock and highly correlated (r² = 0.99). There were two significant haplotypes (by the sequence of rs8082252, rs8082142): AT (χ2 = 7.734, p = 0.0054) and GC (χ2 = 6.874, p = 0.0087). Conclusions: This study provided supportive evidence of the involvement of the kynurenine pathway in IFN-α-induced depression. SNPs in this pathway were also predictive of this disease. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

15 pages, 790 KiB

Open AccessArticle

Expression of Selected Genes Involved in Neurogenesis in the Etiopathogenesis of Depressive Disorders

by Katarzyna Bliźniewska-Kowalska, Piotr Gałecki, Janusz Szemraj and Monika Talarowska

J. Pers. Med. 2021, 11(3), 168; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11030168 - 01 Mar 2021

Cited by 6 | Viewed by 1990

Abstract

(1) Background: The neurogenic theory suggests that impaired neurogenesis within the dentate gyrus of the hippocampus is one of the factors causing depression. Immunology also has an impact on neurotrophic factors. The aim of the study was to assess the importance of selected genes involved in the process of neurogenesis i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and neuron-restrictive silencer factor (REST gene) in the etiopathogenesis of depressive disorders. (2) Methods: A total of 189 subjects took part in the study (95 depressed patients, 94 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). RT-PCR was used to assess gene expression at the mRNA levels, while Enzyme-Linked Immunosorbent Assay (ELISA) was used to assess gene expression at the protein level. (3) Results: Expression of NGF, BDNF, REST genes is lower in depressed patients than in the control group, whereas the expression of GDNF gene is higher in patients with depressive disorders than in the group of healthy volunteers. (4) Conclusions: The expression of selected genes might serve as a biomarker of depression. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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14 pages, 917 KiB

Open AccessArticle

Inflammatory versus Anti-Inflammatory Profiles in Major Depressive Disorders—The Role of IL-17, IL-21, IL-23, IL-35 and Foxp3

by Małgorzata Gałecka, Katarzyna Bliźniewska-Kowalska, Agata Orzechowska, Janusz Szemraj, Michael Maes, Michael Berk, Kuan-Pin Su and Piotr Gałecki

J. Pers. Med. 2021, 11(2), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11020066 - 23 Jan 2021

Cited by 29 | Viewed by 3052

Abstract

Background: The authors of this research study intended to verify whether there are any changes in gene expression in depressed patients without coexisting inflammatory diseases for selected immune-inflammatory factors that are particularly important in autoimmune disease pathogenesis (IL-17, IL-21, IL-23, IL-35, Foxp3). Methods: The study was carried out on a group of 190 patients with depression and 100 healthy volunteers. The severity of depressive symptoms was assessed using the Hamilton Depression Scale. RT-PCR was used to evaluate mRNA expression and ELISA was used to measure protein expression of these genes. Results: The level of gene expression for IL-17, IL-21, IL-23, and IL-35 was substantially higher in the group of patients with depression compared to the control group. The mean mRNA expression of Foxp3 was considerably reduced in patients suffering from depressive disorders. There was a statistically significant correlation between the number of hospitalizations and the expression of specific inflammatory factors. Conclusions: Expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. The duration of the disease seems to be more important for the expression of the genes in question than the severity of depression. These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain as well as be a marker and a new potential therapeutic target for recurrent depressive disorders. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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14 pages, 825 KiB

Open AccessArticle

Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals

by Cheng-Hao Tu, Chun-Ming Chen, Chuan-Chih Yang, Piotr Gałecki and Kuan-Pin Su

J. Pers. Med. 2020, 10(4), 283; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm10040283 - 16 Dec 2020

Cited by 7 | Viewed by 2696

Abstract

N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical compounds, we recruited 24 MDD subjects in this double-blind, head-to-head study with a 12-week EPA or DHA treatment (clinical trial registration number: NCT03871088). The depression severity was assessed by Hamilton depression rating scale (HAM-D). Brain responses to emotional stimuli were measured by a 3-Tesla MRI. The correlation between HAM-D scores and brain responses also were tested. Compared to 18 healthy controls, the brain responses of untreated 24 MDD patients mainly revealed hypoactivity in the regions associated with emotion perception and emotion control when processing positive emotion. After treatment, more remitted MDD patients have been observed in the EPA as compared to the DHA groups. In addition, the EPA, but not DHA, treatment revealed increased activity in the regions associated with emotion perception and cognitive control when processing positive emotion. The correlation analysis further revealed negative correlation between HAM-D scores and brain responses in cognitive control regions. The results of this study may imply the compensatory brain responses of cognitive and emotion controls by EPA but not DHA and underpin personalized medicine with anti-inflammatory nutraceuticals toward depression treatments. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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Review

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19 pages, 689 KiB

Open AccessFeature PaperReview

Diet, Obesity, and Depression: A Systematic Review

by Olivia Patsalos, Johanna Keeler, Ulrike Schmidt, Brenda W. J. H. Penninx, Allan H. Young and Hubertus Himmerich

J. Pers. Med. 2021, 11(3), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11030176 - 03 Mar 2021

Cited by 48 | Viewed by 7833

Abstract

Background: Obesity and depression co-occur in a significant proportion of the population. Mechanisms linking the two disorders include the immune and the endocrine system, psychological and social mechanisms. The aim of this systematic review was to ascertain whether weight loss through dietary interventions has the additional effect of ameliorating depressive symptoms in obese patients. Methods: We systematically searched three databases (Pubmed, Medline, Embase) for longitudinal clinical trials testing a dietary intervention in people with obesity and depression or symptoms of depression. Results: Twenty-four longitudinal clinical studies met the eligibility criteria with a total of 3244 included patients. Seventeen studies examined the effects of calorie-restricted diets and eight studies examined dietary supplements (two studies examined both). Only three studies examined people with a diagnosis of both obesity and depression. The majority of studies showed that interventions using a calorie-restricted diet resulted in decreases in depression scores, with effect sizes between ≈0.2 and ≈0.6. The results were less clear for dietary supplements. Conclusions: People with obesity and depression appear to be a specific subgroup of depressed patients in which calorie-restricted diets might constitute a promising personalized treatment approach. The reduction of depressive symptoms may be related to immunoendocrine and psychosocial mechanisms. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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32 pages, 693 KiB

Open AccessFeature PaperReview

The Importance of Epigenetics in Diagnostics and Treatment of Major Depressive Disorder

by Piotr Czarny, Katarzyna Białek, Sylwia Ziółkowska, Justyna Strycharz, Gabriela Barszczewska and Tomasz Sliwinski

J. Pers. Med. 2021, 11(3), 167; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11030167 - 01 Mar 2021

Cited by 15 | Viewed by 4576

Abstract

Recent studies imply that there is a tight association between epigenetics and a molecular mechanism of major depressive disorder (MDD). Epigenetic modifications, i.e., DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA), are able to influence the severity of the disease and the outcome of the therapy. This article summarizes the most recent literature data on this topic, i.e., usage of histone deacetylases as therapeutic agents with an antidepressant effect and miRNAs or lncRNAs as markers of depression. Due to the noteworthy potential of the role of epigenetics in MDD diagnostics and therapy, we have gathered the most relevant data in this area. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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28 pages, 1845 KiB

Open AccessReview

Treatment-Resistant Depression Revisited: A Glimmer of Hope

by Angelos Halaris, Emilie Sohl and Elizabeth A. Whitham

J. Pers. Med. 2021, 11(2), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11020155 - 23 Feb 2021

Cited by 42 | Viewed by 9445

Abstract

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, and remission is obtained in approximately 30% of patients. This is known as Treatment-Resistant Depression (TRD). The burden of TRD exponentially increases the longer it persists, with a higher risk of impaired functional and social functioning, vast losses in quality of life and significant risk of somatic morbidity and suicidality. Different approaches have been suggested and utilized, but the results have not been encouraging. In this review article, we present new approaches to identify and correct potential causes of TRD, thereby reducing its prevalence and with it the overall burden of this disease entity. We will address potential contributory factors to TRD, most of which can be investigated in many laboratories as routine tests. We discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and thyroid and gonadal dysfunction. We address the role of Vitamin D in contributing to depression. Pharmacogenomic testing is being increasingly used to determine Single Nucleotide Polymorphisms in Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As the role of immune system dysregulation is being recognized as potentially a major contributory factor to TRD, the measurement of C-reactive protein (CRP) and select immune biomarkers, where testing is available, can guide combination treatments with anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. We focus on established and emerging test procedures, potential biomarkers and non-biologic assessments and interventions to apply personalized medicine to effectively manage treatment resistance in general and TRD specifically. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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14 pages, 317 KiB

Open AccessReview

Personalized Medicine Using Neuroimmunological Biomarkers in Depressive Disorders

by Suhyuk Chi and Moon-Soo Lee

J. Pers. Med. 2021, 11(2), 114; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm11020114 - 10 Feb 2021

Cited by 4 | Viewed by 2910

Abstract

Major depressive disorder (MDD) is associated with increased suicidal risk and reduced productivity at work. Neuroimmunology, the study of the immune system and nervous system, provides further insight into the pathogenesis and outcome of MDD. Cytokines are the main modulators of neuroimmunology, and their levels are somewhat entangled in depressive disorders as they affect depressive symptoms and are affected by antidepressant treatment. The use of cytokine-derived medication as a treatment option for MDD is currently a topic of interest. Although not very promising, cytokines are also considered as possible prognostic or diagnostic markers for depression. The machine learning approach is a powerful tool for pattern recognition and has been used in psychiatry for finding useful patterns in data that have translational meaning and can be incorporated in daily clinical practice. This review focuses on the current knowledge of neuroimmunology and depression and the possible use of machine learning to widen our understanding of the topic. Full article

(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)

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