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Brain Sciences
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The Biomarkers in Neuropsychiatric Disorders
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The Biomarkers in Neuropsychiatric Disorders

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Psychiatric Diseases".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 24681

Special Issue Editor

Dr. Bhaskar Roy

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Guest Editor
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Interests: MDD. Suicide; epigenomics; gene regulatory network; exosome

Special Issue Information

Dear Colleagues,

Neuropsychiatric disorders are associated with changes in brain neuronal and non-neuronal circuits. Often, changes are colinear with altered neurochemistry of the diseased brain and display a broad spectrum of behavioral maladies along with cognitive impairments. Given the complex nature of neuropsychiatric disorders, especially the symptomatic ambiguities between the disorders, it is needless to highlight the role of biomarkers in the diagnosis and prognosis of distinguishable neuropathologies between each neuropsychiatric condition. Recent advancements in understanding the varied omics biology of the psychiatric brain combined with progress in big data analysis approaches have reinvigorated the long-standing need for various biomarker discoveries in this field. With the help of recently emerging techniques such as high-resolution imaging, scanning, and blood-based fast screening tools, the list could be substantially stretched out to include exploratory biomarkers for early risk assessment and, most notably, the biomarker for predictable response to treatment. However, extreme cautionary measures should be in place to test the validity of biomarkers before they are introduced into clinical practice. This is especially warranted to underpin the right pathophysiological changes in the neuropsychiatric brain and cannot be achieved by deconstructing the behavioral manifestations of the impacted individual based on interviews and questionaries.    

This Special Issue is aimed to discuss the recent scope of biomarker discoveries and their potential use in the diagnosis and treatment of major neuropsychiatric disabilities. The issue is also focused on highlighting recent developments in imaging- and non-imaging-based biomarkers that have made significant contributions to advancing the ability of clinicians to assess patients and devising a more personalized treatment regime.    

We are looking for all kinds of original research and review articles that may help to further advance the current knowledge and understanding of biomarkers in the neuropsychiatric field. Additionally, we will appreciate expert comments and remarks on cutting-edge technologies associated with novel biomarker discovery and the path to future biomarker discovery which will possibly help in strengthening the clinical settings.

Dr. Bhaskar Roy
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 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

  • non-invasive biomarker
  • peripheral circulation
  • exosome
  • non-coding RNA
  • psychopathology
  • brain

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Published Papers (7 papers)

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Research

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16 pages, 1592 KiB  
Article
PsychArray-Based Genome Wide Association Study of Suicidal Deaths in India
by Chittaranjan Behera, Ruchika Kaushik, Deepak Ramkumar Bharti, Baibaswata Nayak, Daya Nand Bhardwaj, Dibyabhaba Pradhan and Harpreet Singh
Brain Sci. 2023, 13(1), 136; https://doi.org/10.3390/brainsci13010136 - 12 Jan 2023
Cited by 2 | Viewed by 2205
Abstract
Background: Suicide is a preventable but escalating global health crisis. Genome-wide association studies (GWAS) studies to date have been limited, and some are underpowered. In this study, we aimed to perform the PsychArray-based GWAS study to identify single nucleotide variations associated with suicide [...] Read more.
Background: Suicide is a preventable but escalating global health crisis. Genome-wide association studies (GWAS) studies to date have been limited, and some are underpowered. In this study, we aimed to perform the PsychArray-based GWAS study to identify single nucleotide variations associated with suicide in the Indian population. Methods: We recruited unrelated subjects who died by suicide as cases (N = 313) and the non-suicidal deaths as controls (N = 294). The 607 samples were genotyped, including cases and controls using the Illumina Infinium PsychArray-24 BeadChip v1.3 Results: In our study, four single nucleotide polymorphisms (SNPs) crossed the threshold of significance level <1 × 10−5. One of them is intronic at Chromosome2:rs1901851 and three are intergenic at Chromosome12:rs3847911, Chromosome8:rs2941489, Chromosome8:rs1464092. At a significance level of 5 × 10−5, we found a few more SNPs, with the majority of them being intergenic variants. The associated genes were associated with various important functions ranging from cell signaling, GTP binding, GPCR binding, and transcription factor binding. Conclusions: The SNPs identified in our study were not reported earlier. To our best knowledge, this study is one of the first GWAS for suicide in the Indian population. The results indicate few novel SNPs that may be associated with suicide and require further investigation. Their clinical significance is to be studied in the future. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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11 pages, 13771 KiB  
Article
MiR-15b-5p Expression in the Peripheral Blood: A Potential Diagnostic Biomarker of Autism Spectrum Disorder
by Rie Hosokawa, Yuta Yoshino, Yu Funahashi, Fumie Horiuchi, Jun-ichi Iga and Shu-ichi Ueno
Brain Sci. 2023, 13(1), 27; https://doi.org/10.3390/brainsci13010027 - 22 Dec 2022
Cited by 4 | Viewed by 2238
Abstract
Background: Autism spectrum disorder (ASD), is a neurodevelopmental disorder that is known to have a high degree of heritability. Diagnosis of ASD is difficult because of the high heterogeneity of the clinical symptoms. MicroRNAs (miRNAs) can potentially be diagnostic biomarkers for ASD, and [...] Read more.
Background: Autism spectrum disorder (ASD), is a neurodevelopmental disorder that is known to have a high degree of heritability. Diagnosis of ASD is difficult because of the high heterogeneity of the clinical symptoms. MicroRNAs (miRNAs) can potentially be diagnostic biomarkers for ASD, and several studies have shown the relationship between miRNAs and ASD pathogenesis. In this study, we investigated ten miRNA and mRNA expression of target genes in peripheral blood to explore a diagnostic biomarker for ASD. Methods: We recruited control and ASD subjects for the discovery cohort (n = 6, each) and replication cohort (n = 20, each). Using qPCR, miRNA and mRNA expression was measured using the SYBR green and probe methods, respectively. In-silico prediction was used for identifying target genes of miRNAs. An in vitro experiment using HEK293 cells was conducted to investigate whether miR-15b-5p modulates the predicted target genes (TGFBR3 and MYBL1). Results: miR-15b-5p expression indicated an increased trend in the discovery cohort (p = 0.052) and a significant upregulation in the replication cohort (p = 0.021). In-silico analysis revealed that miR-15b-5p is relevant to cell development and Wnt signaling. The decreased trends of TGFBR3 and MYBL expression were the same as in previous RNA-seq data. MiR-15b-5p positively regulated TGFBR3 expression in in vitro experiments. Conclusions: Upregulated miR-15b-5p expression may represent a useful diagnostic marker of ASD subjects, and it may regulate TGFBR3 mRNA expression. These findings indicate a new perspective in the understanding of the pathogenesis of ASD. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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16 pages, 885 KiB  
Article
Occupational Burnout Is Linked with Inefficient Executive Functioning, Elevated Average Heart Rate, and Decreased Physical Activity in Daily Life - Initial Evidence from Teaching Professionals
by Mia Pihlaja, Pipsa P. A. Tuominen, Jari Peräkylä and Kaisa M. Hartikainen
Brain Sci. 2022, 12(12), 1723; https://doi.org/10.3390/brainsci12121723 - 16 Dec 2022
Cited by 11 | Viewed by 5926
Abstract
Burnout is becoming a global pandemic jeopardizing brain health, with a huge impact on quality of life, available workforce, and the economy. Knowledge of the impact of burnout on cognition, physiology, and physical activity (PA) in daily life allows for an improved understanding [...] Read more.
Burnout is becoming a global pandemic jeopardizing brain health, with a huge impact on quality of life, available workforce, and the economy. Knowledge of the impact of burnout on cognition, physiology, and physical activity (PA) in daily life allows for an improved understanding of the health consequences and everyday ramifications of burnout. Twenty-eight volunteers participated in a three-day recording of daily physiology and PA, including heart rate (HR) and daily steps, with a wearable device. They filled in questionnaires screening for burnout (BBI-15), depression (BDI), and executive functions (EFs) in daily life (BRIEF-A). The subjects with burnout had more challenges in EFs, higher average HRs and lower numbers of steps in daily life than those without it. The BBI-15 scores correlated positively with the BDI scores and BRIEF-A indices and negatively with the awake HR variability (HRV) and daily steps. The metacognition index correlated negatively with the HRV. In conclusion, burnout is linked with compromised EFs along with alterations in cardiac physiology and PA in daily life. Such alterations may be easily detected with wearable devices, opening possibilities for novel biomarkers of burnout and other neuropsychiatric disorders. We suggest that physical activity and heart and brain health are intimately intertwined and that burnout interacts with each of them bidirectionally. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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9 pages, 268 KiB  
Article
White Blood Cell and Platelet Counts Are Not Suitable as Biomarkers in the Differential Diagnostics of Dementia
by Sebastian Schröder, Johannes Heck, Adrian Groh, Helge Frieling, Stefan Bleich, Kai G. Kahl, Jacobus J. Bosch, Benjamin Krichevsky and Martin Schulze-Westhoff
Brain Sci. 2022, 12(11), 1424; https://doi.org/10.3390/brainsci12111424 - 23 Oct 2022
Cited by 8 | Viewed by 2031
Abstract
Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood [...] Read more.
Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet counts, as well as C-reactive protein (CRP), have emerged as biomarkers. Their clinical relevance in dementia, however, is currently only insufficiently investigated. In the present study, hematological and inflammatory parameters were measured in the peripheral blood of 97 patients admitted to the gerontopsychiatric ward of Hannover Medical School, a university hospital in Germany, for dementia assessment. The study population comprised 20 non-demented, depressed patients (control group) and 77 demented patients who were assigned to five different groups based on their underlying dementia etiology: AD, n = 33; vascular dementia, n = 12; mixed dementia, n = 21; FTD, n = 5; and Korsakoff syndrome, n = 6. We observed neither statistically significant differences regarding total WBC populations, platelet counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, nor CRP levels between the control group and the five dementia groups. CRP levels tended to be higher in patients with Korsakoff syndrome than in the control group and in AD patients. Thus, CRP could possibly play a role in the differential diagnosis of dementia. This should be investigated further in future prospective studies with larger sample sizes. WBC and platelet counts, by contrast, do not appear to be suitable biomarkers in the differential diagnosis of dementia. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
12 pages, 1054 KiB  
Article
Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammatory Index in Different States of Bipolar Disorder
by Katerina Dadouli, Michel B. Janho, Apostolia Hatziefthimiou, Ioanna Voulgaridi, Konstantina Piaha, Lemonia Anagnostopoulos, Panagiotis Ntellas, Varvara A. Mouchtouri, Konstantinos Bonotis, Nikolaos Christodoulou, Matthaios Speletas and Christos Hadjichristodoulou
Brain Sci. 2022, 12(8), 1034; https://doi.org/10.3390/brainsci12081034 - 4 Aug 2022
Cited by 26 | Viewed by 4535
Abstract
The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We [...] Read more.
The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We conducted a case-control study recruiting 180 BD patients and 407 healthy controls. BD patients who met the inclusion criteria and were hospitalized due to BD at the psychiatry clinic of the University General Hospital of Larisa, Greece, until September 2021 were included in the study. Among them, 111 patients experienced a manic episode and 69 patients experienced a depressive episode. Data including a complete blood count were retrieved from their first admission to the hospital. Bipolar patients had a higher NLR, MLR and SII index compared to healthy controls when they were experiencing a manic episode (p < 0.001) and a depressive episode (p < 0.001). MLR was increased with large effect size only in patients expressing manic episodes. Neutrophils and NLR had the highest area under the curve with a cutoff of 4.38 and 2.15 in the ROC curve, respectively. Gender-related differences were mainly observed in the SII index, with males who were expressing manic episodes and females expressing depressive episodes having an increased index compared to healthy controls. The NLR, MLR and SII index were significantly higher in patients with BD than in healthy controls, which implies a higher grade of inflammation in BD patients. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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Review

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16 pages, 719 KiB  
Review
Biomarkers of Relapse in Cocaine Use Disorder: A Narrative Review
by Margaux Poireau, Thomas Milpied, Angéline Maillard, Christine Delmaire, Emmanuelle Volle, Frank Bellivier, Romain Icick, Julien Azuar, Cynthia Marie-Claire, Vanessa Bloch and Florence Vorspan
Brain Sci. 2022, 12(8), 1013; https://doi.org/10.3390/brainsci12081013 - 30 Jul 2022
Cited by 9 | Viewed by 3674
Abstract
Introduction: Cocaine use disorder is a chronic disease with severe consequences and a high relapse rate. There is a critical need to explore the factors influencing relapse in order to achieve more efficient treatment outcomes. Furthermore, there is a great need for easy-to-measure, [...] Read more.
Introduction: Cocaine use disorder is a chronic disease with severe consequences and a high relapse rate. There is a critical need to explore the factors influencing relapse in order to achieve more efficient treatment outcomes. Furthermore, there is a great need for easy-to-measure, repeatable, and valid biomarkers that can predict treatment response or relapse. Methods: We reviewed the available literature on the Pubmed database concerning the biomarkers associated with relapse in CUD, including central nervous system-derived, genetic, immune, oxidative stress, and “other” biomarkers. Results: Fifty-one articles were included in our analysis. Twenty-five imaging brain anatomic and function assessment studies, mostly using fMRI, examined the role of several structures such as the striatum activity in abstinence prediction. There were fewer studies assessing the use of neuropsychological factors, neurotrophins, or genetic/genomic factors, immune system, or oxidative stress measures to predict abstinence. Conclusion: Several biomarkers have been shown to have predictive value. Prospective studies using combined multimodal assessments are now warranted. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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15 pages, 294 KiB  
Review
Prognostic Significance of Blood-Based Baseline Biomarkers in Treatment-Resistant Depression: A Literature Review of Available Studies on Treatment Response
by Theano Gkesoglou, Stavroula I. Bargiota, Eleni Iordanidou, Miltiadis Vasiliadis, Vasilios-Panteleimon Bozikas and Agorastos Agorastos
Brain Sci. 2022, 12(7), 940; https://doi.org/10.3390/brainsci12070940 - 18 Jul 2022
Cited by 8 | Viewed by 3143
Abstract
Major depressive disorder is a leading cause of disability worldwide and a major contributor to the overall global burden of disease. While there are several options for antidepressant treatment, only about 40–60% of patients respond to initial monotherapy, while 30–40% of patients may [...] Read more.
Major depressive disorder is a leading cause of disability worldwide and a major contributor to the overall global burden of disease. While there are several options for antidepressant treatment, only about 40–60% of patients respond to initial monotherapy, while 30–40% of patients may even show resistance to treatment. This article offers a narrative review of those studies evaluating the predictive properties of various blood-based baseline biomarkers regarding treatment responses to the pharmacological, stimulation, or behavioral treatment of patients with treatment-resistant depression (TRD). Our results show that overall, there is only a very limited number of studies assessing baseline peripheral biomarkers regarding treatment response in TRD. Although there is some evidence for the predictive significance of particular biomarkers (e.g., IL-6, CRP, BDNF), the majority of the results are either single-study reports or studies with conflicting results. This may contribute to the wide variety of treatment protocols and different TRD definition criteria, the small number of patients included, and the existence of different biological phenotypes of the disorder used within the various studies. Taken together, there does not yet appear to be any specific baseline peripheral biomarker with sufficient discriminative predictive validity that can be used in the routine clinical practice of TRD. The discovery of new biomarkers and the better clinical characterization of known biomarkers could support the better classification and staging of TRD, the development of personalized treatment algorithms with higher rates of remission and fewer side effects, and the development of new precision drugs for specific subgroups of patients. Full article
(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)
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