Special Issue "Advances in Markers of Psychiatric Disorders"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Psychiatry".

Deadline for manuscript submissions: 31 March 2021.

Special Issue Editor

Prof. Dr. Napoleon Waszkiewicz
Website
Guest Editor
Medical University of Białystok
Interests: Behavioral Pharmacology; Clinical Neurophysiology; Neuropsychopharmacology; Psychopharmacology; Sleep Disorders; Alcohol Addiction; Smoking; Eating Disorders; Glycoconjugates; Epidemiology

Special Issue Information

Dear Colleagues,

Psychiatric disorders (mental illness) constitute a wide group of disorders, including depression, bipolar disorder, schizophrenia and other psychoses, anxiety disorders, substance-related disorders, dementia, and developmental disorders, e.g., autism. They have a specific behavioral and mental pattern, and characterized by a combination of abnormal thoughts, perceptions, emotions, behaviour, and relationships with others. They can be persistent, relapsing/remitting, or can occur as a single episode. Psychiatric disorders significantly worsen the lives of the people suffering from them. Up to one third of world’s population has some kind of a psychiatric disorder in a given year. These disorders affect the entire structure of people's lives, and cause significant distress or impairment of personal functioning, deteriorating quality of life and the course of somatic diseases. The diagnosis of mental disorders at an early stage allows for early treatment and/or psychotherapy, before the maximum severity of symptoms and hospitalization occur. With the current rapid social development and technology, we have many diagnostic options, such as biochemical, neuroimaging, neurophysiological, neurocognitive and the most commonly used: clinical. Biochemical tests are carried out using many body fluids. Currently, salivary diagnostics in psychiatry is increasing, as saliva contains a wide array of compounds which sensitively respond to biochemical changes in the organism, reflecting the real-time level of these markers, and can be taken in a non-invasive way, which reduces the patient’s stress. Biomarkers are tools used to more accurately identify high-risk individuals, speed up diagnosis, and help increase the likelihood of successful treatment and prognosis determination. The goal of this Special Issue is to summarize new advances in the markers of psychiatric disorders, including depression, bipolar disorder, schizophrenia and other psychoses, anxiety disorders, substance-related disorders, dementia, and developmental disorders such as autism. Original research and review articles are both welcome in order to best understand the importance of different markers of psychiatric illness. Potential topics include but are not limited to the following: advances in clinical markers of psychiatric disorders, advances in molecular and biochemical markers of psychiatric disorders, advances in (neuro)imaging markers of psychiatric disorders, advances in neurophysiological markers of psychiatric disorders, advances in neurocognitive markers of psychiatric disorders, and advances in markers of successful treatment in psychiatry.

Prof. Dr. Napoleon Waszkiewicz
Guest Editor

Manuscript Submission Information

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Keywords

  • psychiatric disorders
  • markers
  • biochemical
  • neuroimaging
  • neurophysiological
  • neurocognitive
  • clinical

Published Papers (11 papers)

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Editorial

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Open AccessEditorial
Mentally Sick or Not—(Bio)Markers of Psychiatric Disorders Needed
J. Clin. Med. 2020, 9(8), 2375; https://doi.org/10.3390/jcm9082375 - 25 Jul 2020
Cited by 4
Abstract
Psychiatric disorders, also called mental illnesses or mental disorders, constitute a wide group of disorders including major depression disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ) and other psychoses, anxiety disorders (ANX), substance-related disorders (SRD), dementia, developmental disorders e [...] Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Research

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Open AccessArticle
Salivary Carbohydrate-Deficient Transferrin in Alcohol- and Nicotine-Dependent Males
J. Clin. Med. 2020, 9(12), 4054; https://doi.org/10.3390/jcm9124054 - 15 Dec 2020
Abstract
Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be [...] Read more.
Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessArticle
Is Interleukin 17 (IL-17) Expression A Common Point in the Pathogenesis of Depression and Obesity?
J. Clin. Med. 2020, 9(12), 4018; https://doi.org/10.3390/jcm9124018 - 12 Dec 2020
Abstract
(1) Background: Activated immune-inflammatory pathways play an important role in the pathogenesis of depression and pathological obesity. Obesity might promote production of cytokine interleukin 17, which plays a significant role in neuro-immune reactions. The study aimed at assessing the relationship between Body Mass [...] Read more.
(1) Background: Activated immune-inflammatory pathways play an important role in the pathogenesis of depression and pathological obesity. Obesity might promote production of cytokine interleukin 17, which plays a significant role in neuro-immune reactions. The study aimed at assessing the relationship between Body Mass Index (BMI) and IL-17 expression, taking into account the clinical psychiatric variables in patients with depression. (2) Methods: A total of 125 participants took part in the study (95 depressed patients, 30 healthy controls). Data concerning the course of depressive disorders and BMI were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Reverse transcription polymerase chain reaction (RT-PCR) was used to assess IL-17 gene expression at the mRNA levels, while enzyme-linked immunosorbent assay (ELISA) was used to assess IL-17 expression at the protein level. (3) Results: Patients with more hospitalizations showed significantly higher IL-17 mRNA expression levels and higher BMI. However, no correlation between BMI and IL-17 expression was found in depressed patients. (4) Conclusions: Our study revealed that BMI does not affect IL-17 expression in patients with depression. However, further studies should be conducted to evaluate the effects of IL-17 inhibition on adipose tissue and vice versa. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessFeature PaperArticle
Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study
J. Clin. Med. 2020, 9(12), 3918; https://doi.org/10.3390/jcm9123918 - 02 Dec 2020
Abstract
In people with depression, immune dysfunctions have been linked with treatment non-response, but examinations of psychological therapy outcomes, particularly longitudinal biomarker studies, are rare. This study investigated relationships between inflammation, depressive subtypes and clinical outcomes to psychological therapy. Adults with depression (n [...] Read more.
In people with depression, immune dysfunctions have been linked with treatment non-response, but examinations of psychological therapy outcomes, particularly longitudinal biomarker studies, are rare. This study investigated relationships between inflammation, depressive subtypes and clinical outcomes to psychological therapy. Adults with depression (n = 96) were assessed before and after a course of naturalistically-delivered psychological therapy. In total, 32 serum inflammatory proteins were examined alongside therapy outcomes and depressive subtypes (somatic/cognitive symptom subtype, and bipolar/unipolar depression). Overall, 49% of participants responded to treatment. High levels of tumour necrosis factor (TNFα), interleukin-6 (IL-6) and soluble intracellular adhesion molecule-1 (sICAM1), and low interferon-γ (IFNγ), preceded a poorer response to therapy. After therapy, non-responders had elevated c-reactive protein (CRP), thymus and activation-regulated chemokine (TARC) and macrophage chemoattractant protein-4 (MCP4), and attenuated IFNy. Non-somatic depressive symptoms were universally not associated with proteins, while somatic-depressive symptom severity was positively correlated with several pro-inflammatory markers. In the somatic subgroup only, IL-6 and serum amyloid alpha (SAA) decreased between pre- and post-therapy timepoints. Regardless of treatment response, IL-7, IL-8, IL-15 and IL-17 increased over time. These results suggest that inflammation is associated with somatic symptoms of depression and non-response to psychological therapy. Future work may enhance the prospective prediction of treatment-response by examining larger samples of individuals undertaking standardised treatment programmes. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessArticle
The Effect of Smartphone-Based Cognitive Training on the Functional/Cognitive Markers of Schizophrenia: A One-Year Randomized Study
J. Clin. Med. 2020, 9(11), 3681; https://doi.org/10.3390/jcm9113681 - 16 Nov 2020
Abstract
Background: Cognitive impairment is associated with long-term disability that results in the deterioration of both the social and professional status of individuals with schizophrenia. The impact of antipsychotic therapy on cognitive function is insufficient. Cognitive training is therefore proposed as a tool for [...] Read more.
Background: Cognitive impairment is associated with long-term disability that results in the deterioration of both the social and professional status of individuals with schizophrenia. The impact of antipsychotic therapy on cognitive function is insufficient. Cognitive training is therefore proposed as a tool for cognitive rehabilitation in schizophrenia. In this study we investigated the effect of self-administered cognitive training using a smartphone-based application on the cognitive function of paranoid schizophrenia patients focusing on response time, correct answer rate, incorrect answer rate, and fatigability to check, if these functions can be functional markers of successful cognitive-smartphone rehabilitation. Methods: 1-year multicenter, open-label randomized study was conducted on 290 patients in a state of symptomatic remission. 191 patients were equipped with the full version of the application and conducted cognitive training twice a week. Reference group (n = 99) was provided with a version of the application having only limited functionality, testing the cognitive performance of patients every 6 months. Results: Statistically significant improvement was observed in both the rate of correct answers (by 4.8%, p = 0.0001), and cognitive fatigability (by 2.9%, p = 0.0001) in the study group, along with a slight improvement in the rate of incorrect answers (by 0.9%, p = 0.15). In contrast, the reference group, who performed cognitive training every 6 months, demonstrated no significant changes in any cognitive activities. Conclusions: Cognitive trainings facilitated by a smartphone-based application, performed regularly for a longer period of time are feasible and may have the potential to improve the cognitive functioning of individuals with schizophrenia. Correct answers and cognitive fatigability have potential to be functional markers of successful smartphone-based psychiatric rehabilitations in schizophrenia patients. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessArticle
The Activity of N-acetyl-β-hexosaminidase in the Blood, Urine, Cerebrospinal Fluid and Vitreous Humor Died People Due to Alcohol Intoxication
J. Clin. Med. 2020, 9(11), 3636; https://doi.org/10.3390/jcm9113636 - 12 Nov 2020
Abstract
Background: The article aimed to assess the activity of the hexosaminidase (HEX) and its HEX A and HEX B isoenzymes in persons who suddenly died due to ethanol poisoning and explain the cause of their death. Methods: The research involved two groups of [...] Read more.
Background: The article aimed to assess the activity of the hexosaminidase (HEX) and its HEX A and HEX B isoenzymes in persons who suddenly died due to ethanol poisoning and explain the cause of their death. Methods: The research involved two groups of the deceased group A—22 people (20 males, 2 females; the average age 46 years) who died due to alcohol intoxication (with the blood alcohol content of 4‰ and above in all biological materials at the time of death—blood, urine, cerebrospinal fluid, and vitreous humor), and group B—30 people (22 males, 8 females; the average age 54 years), who died suddenly due to other reasons than alcohol. Results: The highest activity of the HEX was found in the serum of A and B groups. A significantly lower activity of HEX, HEX A, and HEX B was observed in the urine of group A in comparison to the sober decedents. Conclusion: The lower activity of HEX and its isoenzymes in the dead’s urine due to ethanol poisoning may suggest its usefulness as a potential marker of harmful alcohol drinking. Damage done to the kidneys by ethanol poisoning may be one of the possible mechanisms leading to death. Kidneys may be damaged intravitally via the inflammatory agent. Thus, it is necessary to conduct further research to evaluate the diagnostic usefulness of exoglycosidases while determining the death mechanisms of people who lost their lives due to ethanol poisoning. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessArticle
The Relationship between Suicide and Oxidative Stress in a Group of Psychiatric Inpatients
J. Clin. Med. 2020, 9(11), 3462; https://doi.org/10.3390/jcm9113462 - 28 Oct 2020
Abstract
Diagnosis of suicide risk is a clinical challenge requiring an interdisciplinary therapeutic approach. Except for psychological explanation of the suicidal mechanism, there is evidence that it is associated with brain chemistry disturbances as oxidative stress. The objective of this study was to explore [...] Read more.
Diagnosis of suicide risk is a clinical challenge requiring an interdisciplinary therapeutic approach. Except for psychological explanation of the suicidal mechanism, there is evidence that it is associated with brain chemistry disturbances as oxidative stress. The objective of this study was to explore the role of oxidative stress components in suicidality comparing subjects at different stages of suicide. The study included psychiatric inpatients aged 18–64 (n = 48) with different psychiatric diagnoses. Blood specimens were collected from subjects and tested for oxidative stress biomarkers: superoxide dismutase (SOD), dityrozine (DT), oxidative stress index (OSI), glutathione peroxidase (GPx), total antioxidant capacity (TAC trolox), ferric reducing ability of plasma (FRAP), total oxidant status (TOS), catalase (CAT), advanced glycoxidation end products (AGE), NADPH oxidase (NOX), and advanced oxidation protein products (AOPP). The Columbia Severity Suicide Scale (C-SSRS) was used for suicidality assessment. Subjects with a history of suicide ideations over the last three months had significantly higher levels of NOX, AOPP, and OSI. There was no significant relationship to any oxidative stress component levels either with a history of suicide behaviors or with suicide attempts over the last three months. The levels of NOX and AOPP were both positively correlated to the intensity of suicidal thoughts. Moreover, there was a positive correlation between a number of suicide attempts during a lifetime with AGE and DT and negative with CAT. Similarly, the subjects with a history of suicide attempts had significantly higher AGE and DT levels and lower CAT values. The study confirmed that oxidative stress plays an important role in the pathophysiology of suicide and specific oxidative stress measures vary in suicidal and non-suicidal psychiatric inpatients. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessArticle
Differentiating Females with Rett Syndrome and Those with Multi-Comorbid Autism Spectrum Disorder Using Physiological Biomarkers: A Novel Approach
J. Clin. Med. 2020, 9(9), 2842; https://doi.org/10.3390/jcm9092842 - 02 Sep 2020
Abstract
This study explored the use of wearable sensor technology to investigate autonomic function in children with autism spectrum disorder (ASD) and Rett syndrome (RTT). We aimed to identify autonomic biomarkers that can correctly differentiate females with ASD and Rett Syndrome using an innovative [...] Read more.
This study explored the use of wearable sensor technology to investigate autonomic function in children with autism spectrum disorder (ASD) and Rett syndrome (RTT). We aimed to identify autonomic biomarkers that can correctly differentiate females with ASD and Rett Syndrome using an innovative methodology that applies machine learning approaches. Our findings suggest that we can predict (95%) the status of ASD/Rett. We conclude that physiological biomarkers may be able to assist in the differentiation between patients with RTT and ASD and could allow the development of timely therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Review

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Open AccessReview
Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis
J. Clin. Med. 2020, 9(12), 3840; https://doi.org/10.3390/jcm9123840 - 26 Nov 2020
Abstract
Objective: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor [...] Read more.
Objective: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD. Methods: We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I2 statistic. Moderators of effects were explored using metaregression. Results: Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, p < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = −0.1203, p = 0.0004). Conclusions: Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessReview
Peripheral Markers of Depression
J. Clin. Med. 2020, 9(12), 3793; https://doi.org/10.3390/jcm9123793 - 24 Nov 2020
Abstract
Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has [...] Read more.
Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers—C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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Open AccessReview
Diagnostic Utility of Selected Serum Dementia Biomarkers: Amyloid β-40, Amyloid β-42, Tau Protein, and YKL-40: A Review
J. Clin. Med. 2020, 9(11), 3452; https://doi.org/10.3390/jcm9113452 - 27 Oct 2020
Abstract
Introduction: Dementia is a group of disorders that causes dysfunctions in human cognitive and operating functions. Currently, it is not possible to conduct a fast, low-invasive dementia diagnostic process with the use of peripheral blood biomarkers, however, there is a great deal of [...] Read more.
Introduction: Dementia is a group of disorders that causes dysfunctions in human cognitive and operating functions. Currently, it is not possible to conduct a fast, low-invasive dementia diagnostic process with the use of peripheral blood biomarkers, however, there is a great deal of research in progress covering this subject. Research on dementia biomarkers in serum validates anticipated health and economic benefits from early screening tests. Biomarkers are also essential for improving the process of developing new drugs. Methods: The result analysis, of current studies on selected biomarker concentrations (Aβ40, Aβ42, t-tau, and YKL-40) and their combination in the serum of patients with dementia and mild cognitive disorders, involved a search for papers available in Medline, PubMed, and Web of Science databases published from 2000 to 2020. Results: The results of conducted cross-sectional studies comparing Aβ40, Aβ42, and Aβ42/Aβ40 among people with cognitive disorders and a control group are incoherent. Most of the analyzed papers showed an increase in t-tau concentration in diagnosed Alzheimer’s disease (AD) patients’ serum, whereas results of mild cognitive impairment (MCI) groups did not differ from the control groups. In several papers on the concentration of YKL-40 and t-tau/Aβ42 ratio, the results were promising. To date, several studies have only covered the field of biomarker concentrations in dementia disorders other than AD. Conclusions: Insufficient amyloid marker test repeatability may result either from imperfection of the used laboratorial techniques or inadequate selection of control groups with their comorbidities. On the basis of current knowledge, t-tau, t-tau/Aβ42, and YKL-40 seem to be promising candidates as biomarkers of cognitive disorders in serum. YKL-40 seems to be a more useful biomarker in early MCI diagnostics, whereas t-tau can be used as a marker of progress of prodromal states in mild AD. Due to the insignificant number of studies conducted to date among patients with dementia disorders other than AD, it is not possible to make a sound assessment of their usefulness in dementia differential diagnostics. Full article
(This article belongs to the Special Issue Advances in Markers of Psychiatric Disorders)
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