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Brain Sciences
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Anxious Brain: Stress Influence on the Nervous System
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Anxious Brain: Stress Influence on the Nervous System

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 12176

Special Issue Editor

Prof. Dr. Drozdstoi Stoyanov

E-Mail Website1 Website2
Guest Editor
Department of Psychiatry and Medical Psychology and Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
Interests: psychopathology; psychological assessment; neurobiology; neuroimaging; genetics; immunology; DSM; mental illness; treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Anxiety disorders, including generalized anxiety, panic disorder, and posttraumatic stress, constitute the most frequent mental disorders, and occur in about 14–18% of the overall population. They can greatly affect quality of life, especially in young adults. In this Special Issue, we aim to examine the interrelations between environmental stress factors, such as psychological, and biological (oxidative) and substance misuse, and their impact on the brain structure and function. We will also consider the pivotal role of shifting forms of stress in modern society, due to dynamic changes in lifestyle.

It is clear that anxiety and mood disorders also share some clinical features and underlying mechanisms, notably depressive and anxiety disorders which occur as a consequence of adaptation challenges and in response to critical stressful life events. This raises questions about endogenic conditions and “psychogenic” psychopathological reactions, according to Carl Jaspers.

Therefore, our Special Issue is open to contributions explaining the mechanisms and stress–diathesis interactions across the whole spectrum of affective disorders and their comorbidities.

Prof. Dr. Drozdstoy Stoyanov
Guest Editor

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. Brain Sciences 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 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

  • anxiety
  • depression
  • stress
  • post-traumatic stress
  • neuroscience

Published Papers (8 papers)

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11 pages, 734 KiB  
Article
Conversion and Obsessive–Phobic Symptoms Predict IL-33 and IL-28A Levels in Individuals Diagnosed with COVID-19
by Kristina Stoyanova, Drozdstoy Stoyanov, Steliyan Petrov, Alexandra Baldzhieva, Martina Bozhkova, Mariana Murdzheva, Teodora Kalfova, Hristina Andreeva, Hristo Taskov, Petar Vassilev and Angel Todev
Brain Sci. 2023, 13(9), 1271; https://doi.org/10.3390/brainsci13091271 - 31 Aug 2023
Viewed by 830
Abstract
The first epidemiological wave of the incidence of COVID-19 in Bulgaria was registered in June 2020. After the wave peak, we conducted a study in persons diagnosed with COVID-19 (N = 52). They were assessed with the anxiety–depressive scale (ADS), including basic (BS), [...] Read more.
The first epidemiological wave of the incidence of COVID-19 in Bulgaria was registered in June 2020. After the wave peak, we conducted a study in persons diagnosed with COVID-19 (N = 52). They were assessed with the anxiety–depressive scale (ADS), including basic (BS), vegetative (VS), conversion (CS), obsessive–phobic (OPS), and depressive (DS) symptoms. ADS assessment of individuals diagnosed with SARS-CoV-2 indicated a correlation between OPS and IL-33 values. IL-10 levels were higher than reference ranges in all patients. Multiple linear regression analyses demonstrated that combination of CS and OPS explained 28% of IL-33 levels, while combination of symptoms from all ADS dimensions explained 24% of IL-33 levels. It was also found that 21% of IL-28A levels was explained from the combination by all ADS dimensions, whereas OPS was the predictor for lower concentrations. The obtained results revealed meaningful correlations between psycho neuro–immunological factors in pathogenesis of illness from the coronavirus infection. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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17 pages, 1744 KiB  
Article
Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness
by Michael Maes, Muanpetch Rachayon, Ketsupar Jirakran, Pimpayao Sodsai and Atapol Sughondhabirom
Brain Sci. 2023, 13(7), 1090; https://doi.org/10.3390/brainsci13071090 - 18 Jul 2023
Viewed by 1119
Abstract
Major depressive disorder (MDD) and its severe subtype, major dysmood disorder (MDMD), are distinguished by activation of inflammatory and growth factor subnetworks, which are associated with recurrence of illness (ROI) and adverse childhood experiences (ACEs). Nerve growth factor (NGF) plays a crucial role [...] Read more.
Major depressive disorder (MDD) and its severe subtype, major dysmood disorder (MDMD), are distinguished by activation of inflammatory and growth factor subnetworks, which are associated with recurrence of illness (ROI) and adverse childhood experiences (ACEs). Nerve growth factor (NGF) plays a crucial role in facilitating neuro-immune communications and may regulate the inflammatory response. Methods: The present study examined the effects of ACEs and ROI on culture supernatant NGF, stem cell factor (SCF), stem cell GF (SCGF), hepatocyte GF (HGF), and macrophage colony-stimulating factor (M-CSF), in relation to a neurotoxicity (NT) cytokine profile. Results: NGF levels are lower in MDD (p = 0.003), particularly MDMD (p < 0.001), as compared with normal controls. ROI and ACE were significantly and inversely associated with NGF (≤0.003) and the NGF/NT ratio (≤0.001), whereas there are no effects of ACEs and ROI on SCF, SCGF, HGF, or M-CSF. Lowered NGF (p = 0.003) and the NGF/NT ratio (p < 0.001) are highly significantly and inversely associated with the severity of the current depression phenome, conceptualized as a latent vector extracted from the current severity of depression, anxiety, and suicidal behaviors. We found that one validated and replicable latent vector could be extracted from NGF, ROI, and the depression phenome, which therefore constitutes a novel ROI-NGF-pathway-phenotype. ACEs explained 59.5% of the variance in the latter pathway phenotype (p < 0.001). Conclusions: The imbalance between decreased NGF and increased neurotoxic cytokines during the acute phase of severe depression may contribute to decreased neuroprotection, increased neuro-affective toxicity, and chronic mild inflammation. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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20 pages, 1095 KiB  
Article
Mood Symptoms and Chronic Fatigue Syndrome Due to Relapsing-Remitting Multiple Sclerosis Are Associated with Immune Activation and Aberrations in the Erythron
by Abbas F. Almulla, Al-Karrar Kais Abdul Jaleel, Ali Abbas Abo Algon, Chavit Tunvirachaisakul, Hayder K. Hassoun, Hussein K. Al-Hakeim and Michael Maes
Brain Sci. 2023, 13(7), 1073; https://doi.org/10.3390/brainsci13071073 - 14 Jul 2023
Cited by 1 | Viewed by 1865
Abstract
Background: Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, [...] Read more.
Background: Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. Objectives: The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. Material and Methods: We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables, and used a bio-plex assay to measure 27 serum cytokines. Results: A significant proportion of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, and T helper (Th)1 and Th17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. Conclusions: Around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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15 pages, 954 KiB  
Article
The Cytokine, Chemokine, and Growth Factor Network of Prenatal Depression
by Michael Maes, Yoshiko Abe, Wandee Sirichokchatchawan, Junpen Suwimonteerabutr, Ussanee Sangkomkamhangd, Abbas F. Almulla and Sirina Satthapisit
Brain Sci. 2023, 13(5), 727; https://doi.org/10.3390/brainsci13050727 - 26 Apr 2023
Cited by 3 | Viewed by 1532
Abstract
Background: Neuro-immune pathways are engaged in antenatal and postpartum depression. Aims: To determine if immune profiles influence the severity of prenatal depression above and beyond the effects of adverse childhood experiences (ACE), premenstrual syndrome (PMS), and current psychological stressors. Methods: Using the Bio-Plex [...] Read more.
Background: Neuro-immune pathways are engaged in antenatal and postpartum depression. Aims: To determine if immune profiles influence the severity of prenatal depression above and beyond the effects of adverse childhood experiences (ACE), premenstrual syndrome (PMS), and current psychological stressors. Methods: Using the Bio-Plex Pro human cytokine 27-plex test kit, we assayed M1 macrophage, T helper (Th)-1, Th-2, Th-17, growth factor, chemokine, and T cell growth immune profiles as well as indicators of the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in 120 pregnant females in the early (<16 weeks) and late (>24 weeks) pregnancy. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess severity of antenatal depression. Results: Cluster analyses showed that the combined effects of ACE, relationship dissatisfaction, unwanted pregnancy, PMS, and upregulated M1, Th-1, Th-2, and IRS immune profiles and the ensuing early depressive symptoms shape a stress-immune-depression phenotypic class. Elevated IL-4, IL-6, IL-8, IL-12p70, IL-15, IL-17, and GM-CSF are the cytokines associated with this phenotypic class. All immune profiles (except CIRS) were significantly associated with the early EPDS score, independent of the effects of psychological variables and PMS. There was a shift in immune profiles from early to late pregnancy, with an increase in the IRS/CIRS ratio. The late EPDS score was predicted by the early EPDS score, adverse experiences, and immune profiles, mainly the Th-2 and Th-17 phenotypes. Conclusions: Activated immune phenotypes contribute to early and late perinatal depressive symptoms above and beyond the effects of psychological stressors and PMS. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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20 pages, 2172 KiB  
Article
Research and Diagnostic Algorithmic Rules (RADAR) and RADAR Plots for the First Episode of Major Depressive Disorder: Effects of Childhood and Recent Adverse Experiences on Suicidal Behaviors, Neurocognition and Phenome Features
by Michael Maes and Abbas F. Almulla
Brain Sci. 2023, 13(5), 714; https://doi.org/10.3390/brainsci13050714 - 24 Apr 2023
Cited by 7 | Viewed by 1658
Abstract
Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine [...] Read more.
Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine whether adverse childhood experiences (ACE) and negative life events (NLE) are associated with suicidal behaviors (SB), cognitive impairment, and phenome RADAR scores. This study recruited 90 patients with major depressive disorder (MDD) in an acute phase, of whom 71 showed a first-episode MDD (FEM), and 40 controls. We constructed RADAR scores for ACE; NLE encountered in the last year; SB; and severity of depression, anxiety, chronic fatigue, and physiosomatic symptoms using the Hamilton Depression and Anxiety Rating Scales and the FibroFatigue scale. The partial least squares analysis showed that in FEM, one latent vector (labeled the phenome of FEM) could be extracted from depressive, anxiety, fatigue, physiosomatic, melancholia, and insomnia symptoms, SB, and cognitive impairments. The latter were conceptualized as a latent vector extracted from the Verbal Fluency Test, the Mini-Mental State Examination, and ratings of memory and judgement, indicating a generalized cognitive decline (G-CoDe). We found that 60.8% of the variance in the FEM phenome was explained by the cumulative effects of NLE and ACE, in particular emotional neglect and, to a lesser extent, physical abuse. In conclusion, the RADAR scores and plots constructed here should be used in research and clinical settings, rather than the binary diagnosis of MDD based on the DSM-5 or ICD. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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10 pages, 3647 KiB  
Case Report
Tic Cough in an Adolescent with Organic Brain Pathology—A Case Report and Literature Review
by Agnese Grinevica, Agnese Udre, Arturs Balodis and Ilze Strumfa
Brain Sci. 2024, 14(1), 79; https://doi.org/10.3390/brainsci14010079 - 13 Jan 2024
Viewed by 1059
Abstract
Chronic cough in children and adolescents can be troublesome both to the patient and the whole family. The most common causes of chronic cough in children are protracted bacterial bronchitis and bronchial asthma. However, differential diagnostic workup and treatment can become complicated when [...] Read more.
Chronic cough in children and adolescents can be troublesome both to the patient and the whole family. The most common causes of chronic cough in children are protracted bacterial bronchitis and bronchial asthma. However, differential diagnostic workup and treatment can become complicated when a cough of different etiology is encountered, especially in a child having a complex medical history for an unrelated pathology. A cough lacking any identified somatic cause and response to medical treatment in combination with core clinical features of tics that include suppressibility, distractibility, suggestibility, variability, and the presence of a premonitory sensation is labeled tic cough. Here we discuss a case of an adolescent who had atrophy of the corpus callosum and a history of ventriculoperitoneal shunting due to hydrocephalus caused by stenosis of the sylvian aqueduct, but now presented with a debilitating dry cough lasting for several months. After physical causes of cough were ruled out, the diagnosis of tic cough was reached, and multidisciplinary treatment ensured complete recovery. To the best of our knowledge, this is the first reported case showing coincidence of tic cough and hydrocephalus. The co-occurrence of non-syndromic corpus callosum atrophy and tic cough might hypothetically suggest a predisposing pathogenetic link via reduced signaling through cortical inhibitory neurons; further studies are needed. The importance of careful assessment of medical history, clinical picture, and features of the cough itself are emphasized in order to reach the correct diagnosis. Increased awareness of medical society is mandatory to recognize tic cough and to distinguish it from the neurologic manifestations of organic brain pathology. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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18 pages, 1801 KiB  
Systematic Review
Gene Expression Analysis in Postmortem Brains from Individuals Who Died by Suicide: A Systematic Review
by Thelma Beatriz González-Castro, Alma Delia Genis-Mendoza, María Lilia López-Narváez, Isela Esther Juárez-Rojop, Miguel Angel Ramos-Méndez, Carlos Alfonso Tovilla-Zárate and Humberto Nicolini
Brain Sci. 2023, 13(6), 906; https://doi.org/10.3390/brainsci13060906 - 03 Jun 2023
Cited by 1 | Viewed by 1448
Abstract
Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an increase in gene expression studies has been in development. Through a systematic review, we aimed to find a [...] Read more.
Around the world, more the 700,000 individuals die by suicide every year. It is necessary to understand the mechanisms associated with suicidal behavior. Recently, an increase in gene expression studies has been in development. Through a systematic review, we aimed to find a candidate gene in gene expression studies on postmortem brains of suicide completers. Databases were systematically searched for published studies. We performed an online search using PubMed, Scopus and Web of Science databases to search studies up until May 2023. The terms included were “gene expression”, “expressed genes”, “microarray”, “qRT–PCR”, “brain samples” and “suicide”. Our systematic review included 59 studies covering the analysis of 1450 brain tissues from individuals who died by suicide. The majority of gene expression profiles were obtained of the prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, ventral prefrontal cortex and orbital frontal cortex area. The most studied mRNAs came of genes in glutamate, γ-amino-butyric acid and polyamine systems. mRNAs of genes in the brain-derived neurotrophic factor, tropomyosin-related kinase B (TrkB), HPA axis and chemokine family were also studied. On the other hand, psychiatric comorbidities indicate that suicide by violent death can alter the profile of mRNA expression. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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18 pages, 668 KiB  
Systematic Review
Neuroimaging Correlates of Treatment Response to Transcranial Magnetic Stimulation in Bipolar Depression: A Systematic Review
by Ahmad Shamabadi, Hanie Karimi, Giulia Cattarinussi, Hossein Sanjari Moghaddam, Shahin Akhondzadeh, Fabio Sambataro, Giandomenico Schiena and Giuseppe Delvecchio
Brain Sci. 2023, 13(5), 801; https://doi.org/10.3390/brainsci13050801 - 15 May 2023
Cited by 1 | Viewed by 1721
Abstract
Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions [...] Read more.
Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions for studies investigating neuroimaging biomarkers, through structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT), in association with response to TMS in patients with BD. Eleven studies were included (fMRI = 4, MRI = 1, PET = 3, SPECT = 2, and MRS = 1). Important fMRI predictors of response to repetitive TMS (rTMS) included higher connectivity of emotion regulation and executive control regions. Prominent MRI predictors included lower ventromedial prefrontal cortex connectivity and lower superior frontal and caudal middle frontal volumes. SPECT studies found hypoconnectivity of the uncus/parahippocampal cortex and right thalamus in non-responders. The post-rTMS changes using fMRI mostly showed increased connectivity among the areas neighboring the coil. Increased blood perfusion was reported post-rTMS in PET and SPECT studies. Treatment response comparison between unipolar depression and BD revealed almost equal responses. Neuroimaging evidence suggests various correlates of response to rTMS in BD, which needs to be further replicated in future studies. Full article
(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)
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