Crosstalk between Depression, Anxiety, Dementia, and Chronic Pain: Comorbidity in Behavioral Neurology and Neuropsychiatry Volume III

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 11214

Special Issue Editors


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Guest Editor
Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
Interests: depression; anxiety; dementia pain; their comorbidities nature; translational research in neurological diseases and psychiatric disorders
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Guest Editor
1. Department of Psychology, University of Turin, Turin, Italy
2. Center for Studies and Research in Cognitive Neuroscience, Department of Psychology, University of Bologna, Bologna, Italy
Interests: NIBS techniques; TMS; skin conductance; heart rate variability; fear conditioning; fear learning; learning; neuropsychology; prefrontal cortex; amygdala; hippocampus; anxiety; depression; working memory; PTSD; skin conductance responses; psychophysiology; error-related negativity; EEG; tDCS; Alzheimer’s disease; PIT; stress-related disorders; Parkinson’s disease; resilience; memory; neurologic patients; cognitive decisions; fMRI; translational and molecular psychiatry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This is the third volume of the Special Issue "Crosstalk between Depression, Anxiety, and Dementia: Comorbidity in Behavioral Neurology and Neuropsychiatry".

In the realm of neurodegenerative and psychiatric diseases, symptoms such as depression, anxiety, dementia, and chronic pain span a spectrum and commonly coexist among patients. These illnesses pose significant research challenges due to their polygenic etiologies, multifactorial causative factors, heterogeneous pathogenesis, and diverse mental and behavioral manifestations. The range of diseases exhibiting these symptoms includes Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease and amyotrophic lateral sclerosis, infectious prion disease, stroke sequelae, and psychiatric disorders such as depressive disorder, substance abuse disorder, bipolar disorder, anxiety disorder, schizophrenia, somatic symptom disorder, autism spectrum disorder, post-traumatic stress disorder, and hyperactive attention deficit disorder.

This Special Issue aims to shed light on the latest research pertaining to the comorbidity of depression, anxiety, dementia, and chronic pain in various diseases. We cordially invite authors to contribute original research articles focusing on, but not limited to the following:

  • Etiology, pathogenesis, and progression mechanisms;
  • Early diagnosis including the use of biomarkers, bio-imaging, and biosensors;
  • Prophylactic, disease-modifying, and therapeutic strategies, as well as novel targets;
  • Novel drug discovery and development, naturally driven biomedicines, natural bioactive molecules, and vaccines;
  • Antidepressants, anti-anxiolytics, cognitive enhancers, and analgesics;
  • Nanobiotechnology, nanosimilars, and nanobiosimilars;
  • Preclinical in vitro models and animal models;
  • Bench-to-bedside translational research;
  • Bedside-to-bench translational research.

Review articles including expert opinions, systematic analysis, metanalysis, and other statistical and analytical methods are also welcome.

Dr. Masaru Tanaka
Dr. Simone Battaglia
Guest Editors

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Related Special Issue

Published Papers (6 papers)

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Research

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14 pages, 1210 KiB  
Article
From Mild Cognitive Impairment to Dementia: The Impact of Comorbid Conditions on Disease Conversion
by Federico Menegon, Fabiola De Marchi, Davide Aprile, Iacopo Zanelli, Greta Decaroli, Cristoforo Comi and Giacomo Tondo
Biomedicines 2024, 12(8), 1675; https://doi.org/10.3390/biomedicines12081675 - 26 Jul 2024
Viewed by 931
Abstract
The conversion from mild cognitive impairment (MCI) to dementia is influenced by several factors, including comorbid conditions such as metabolic and vascular diseases. Understanding the impact of these comorbidities can help in the disease management of patients with a higher risk of progressing [...] Read more.
The conversion from mild cognitive impairment (MCI) to dementia is influenced by several factors, including comorbid conditions such as metabolic and vascular diseases. Understanding the impact of these comorbidities can help in the disease management of patients with a higher risk of progressing to dementia, improving outcomes. In the current study, we aimed to analyze data from a large cohort of MCI (n = 188) by principal component analysis (PCA) and cluster analysis (CA) to classify patients into distinct groups based on their comorbidity profile and to predict the risk of conversion to dementia. From our analysis, four clusters emerged. CA showed a significantly higher rate of disease progression for Cluster 1, which was predominantly characterized by extremely high obesity and diabetes compared to other clusters. In contrast, Cluster 3, which was defined by a lower prevalence of all comorbidities, had a lower conversion rate. Cluster 2, mainly including subjects with traumatic brain injuries, showed the lowest rate of conversion. Lastly, Cluster 4, including a high load of hearing loss and depression, showed an intermediate risk of conversion. This study underscores the significant impact of specific comorbidity profiles on the progression from MCI to dementia, highlighting the need for targeted interventions and management strategies for individuals with these comorbidity profiles to potentially delay or prevent the onset of dementia. Full article
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15 pages, 3323 KiB  
Article
Blood Plasma Markers in Depressed Mice under Chronic Social Defeat Stress
by Dmitry A. Smagin, Dmitry V. Bezryadnov, Maria G. Zavialova, Anastasia Yu. Abramova, Sergey S. Pertsov and Natalia N. Kudryavtseva
Biomedicines 2024, 12(7), 1485; https://doi.org/10.3390/biomedicines12071485 - 5 Jul 2024
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Abstract
It has previously been shown that, in mice, chronic social defeat stress in daily agonistic interactions leads to a depression-like state similar to that in depressive patients. With this model, it has become obvious that it is possible to study peripheral markers of [...] Read more.
It has previously been shown that, in mice, chronic social defeat stress in daily agonistic interactions leads to a depression-like state similar to that in depressive patients. With this model, it has become obvious that it is possible to study peripheral markers of the depression-like state in an experiment. This paper was aimed at searching for protein markers in the blood plasma of depressed mice in the chronic social conflict model, which allows for us to obtain male mice with repeated experiences of defeat. Proteomic analysis of blood plasma samples was conducted to identify proteins differentially expressed in this state. There were changes in the expression levels of the amyloid proteins SAA1, SAA4, and SAMP and apolipoproteins APOC3, APOD, and ADIPO in the blood plasma of depressed mice compared with controls (unstressed mice). Changes in the expression of serine protease inhibitors and/or proteins associated with lipid metabolism, inflammation, or immune function [ITIH4, SPA3, A1AT5, HTP (HP), CO9, and A2MG] were also found. Here, we showed that chronic social stress is accompanied by increased levels of amyloid proteins and apolipoproteins in blood plasma. A similarity was noted between the marker protein expression changes in the depressed mice and those in patients with Alzheimer’s disease. These data indicate a psychopathogenic role of chronic social stress, which can form a predisposition to neurodegenerative and/or psychoemotional disorders. Full article
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16 pages, 1040 KiB  
Article
Predictive Models for the Transition from Mild Neurocognitive Disorder to Major Neurocognitive Disorder: Insights from Clinical, Demographic, and Neuropsychological Data
by Anna Tsiakiri, Christos Bakirtzis, Spyridon Plakias, Pinelopi Vlotinou, Konstantinos Vadikolias, Aikaterini Terzoudi and Foteini Christidi
Biomedicines 2024, 12(6), 1232; https://doi.org/10.3390/biomedicines12061232 - 1 Jun 2024
Cited by 1 | Viewed by 1043
Abstract
Neurocognitive disorders (NCDs) are progressive conditions that severely impact cognitive function and daily living. Understanding the transition from mild to major NCD is crucial for personalized early intervention and effective management. Predictive models incorporating demographic variables, clinical data, and scores on neuropsychological and [...] Read more.
Neurocognitive disorders (NCDs) are progressive conditions that severely impact cognitive function and daily living. Understanding the transition from mild to major NCD is crucial for personalized early intervention and effective management. Predictive models incorporating demographic variables, clinical data, and scores on neuropsychological and emotional tests can significantly enhance early detection and intervention strategies in primary healthcare settings. We aimed to develop and validate predictive models for the progression from mild NCD to major NCD using demographic, clinical, and neuropsychological data from 132 participants over a two-year period. Generalized Estimating Equations were employed for data analysis. Our final model achieved an accuracy of 83.7%. A higher body mass index and alcohol drinking increased the risk of progression from mild NCD to major NCD, while female sex, higher praxis abilities, and a higher score on the Geriatric Depression Scale reduced the risk. Here, we show that integrating multiple factors—ones that can be easily examined in clinical settings—into predictive models can improve early diagnosis of major NCD. This approach could facilitate timely interventions, potentially mitigating the progression of cognitive decline and improving patient outcomes in primary healthcare settings. Further research should focus on validating these models across diverse populations and exploring their implementation in various clinical contexts. Full article
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13 pages, 285 KiB  
Article
Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients
by Alessandra Della Vecchia, Ciro De Luca, Lucrezia Becattini, Letizia Curto, Elena Ferrari, Gabriele Siciliano, Sara Gori and Filippo Baldacci
Biomedicines 2024, 12(3), 677; https://doi.org/10.3390/biomedicines12030677 - 18 Mar 2024
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Abstract
The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study [...] Read more.
The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief. Full article
24 pages, 16786 KiB  
Article
Preclinical Evidence for the Role of the Yin/Yang Angiotensin System Components in Autism Spectrum Disorder: A Therapeutic Target of Astaxanthin
by Ayat I. Samra, Ahmed S. Kamel, Dalaal M. Abdallah, Mai A. Abd El Fattah, Kawkab A. Ahmed and Hanan S. El-Abhar
Biomedicines 2023, 11(12), 3156; https://doi.org/10.3390/biomedicines11123156 - 27 Nov 2023
Cited by 2 | Viewed by 1636
Abstract
Autism spectrum disorder (ASD) prevalence is emerging with an unclear etiology, hindering effective therapeutic interventions. Recent studies suggest potential renin–angiotensin system (RAS) alterations in different neurological pathologies. However, its implications in ASD are unexplored. This research fulfills the critical gap by investigating dual [...] Read more.
Autism spectrum disorder (ASD) prevalence is emerging with an unclear etiology, hindering effective therapeutic interventions. Recent studies suggest potential renin–angiotensin system (RAS) alterations in different neurological pathologies. However, its implications in ASD are unexplored. This research fulfills the critical gap by investigating dual arms of RAS and their interplay with Notch signaling in ASD, using a valproic acid (VPA) model and assessing astaxanthin’s (AST) modulatory impacts. Experimentally, male pups from pregnant rats receiving either saline or VPA on gestation day 12.5 were divided into control and VPA groups, with subsequent AST treatment in a subset (postnatal days 34–58). Behavioral analyses, histopathological investigations, and electron microscopy provided insights into the neurobehavioral and structural changes induced by AST. Molecular investigations of male pups’ cortices revealed that AST outweighs the protective RAS elements with the inhibition of the detrimental arm. This established the neuroprotective and anti-inflammatory axes of RAS (ACE2/Ang1-7/MasR) in the ASD context. The results showed that AST’s normalization of RAS components and Notch signaling underscore a novel therapeutic avenue in ASD, impacting neuronal integrity and behavioral outcomes. These findings affirm the integral role of RAS in ASD and highlight AST’s potential as a promising treatment intervention, inviting further neurological research implications. Full article
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Review

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22 pages, 1338 KiB  
Review
Advancements in Understanding and Classifying Chronic Orofacial Pain: Key Insights from Biopsychosocial Models and International Classifications (ICHD-3, ICD-11, ICOP)
by Federica Canfora, Giulia Ottaviani, Elena Calabria, Giuseppe Pecoraro, Stefania Leuci, Noemi Coppola, Mattia Sansone, Katia Rupel, Matteo Biasotto, Roberto Di Lenarda, Michele Davide Mignogna and Daniela Adamo
Biomedicines 2023, 11(12), 3266; https://doi.org/10.3390/biomedicines11123266 - 9 Dec 2023
Cited by 2 | Viewed by 3052
Abstract
In exploring chronic orofacial pain (COFP), this review highlights its global impact on life quality and critiques current diagnostic systems, including the ICD-11, ICOP, and ICHD-3, for their limitations in addressing COFP’s complexity. Firstly, this study outlines the global burden of chronic pain [...] Read more.
In exploring chronic orofacial pain (COFP), this review highlights its global impact on life quality and critiques current diagnostic systems, including the ICD-11, ICOP, and ICHD-3, for their limitations in addressing COFP’s complexity. Firstly, this study outlines the global burden of chronic pain and the importance of distinguishing between different pain types for effective treatment. It then delves into the specific challenges of diagnosing COFP, emphasizing the need for a more nuanced approach that incorporates the biopsychosocial model. This review critically examines existing classification systems, highlighting their limitations in fully capturing COFP’s multifaceted nature. It advocates for the integration of these systems with the DSM-5’s Somatic Symptom Disorder code, proposing a unified, multidisciplinary diagnostic approach. This recommendation aims to improve chronic pain coding standardization and acknowledge the complex interplay of biological, psychological, and social factors in COFP. In conclusion, here, we highlight the need for a comprehensive, universally applicable classification system for COFP. Such a system would enable accurate diagnosis, streamline treatment strategies, and enhance communication among healthcare professionals. This advancement holds potential for significant contributions to research and patient care in this challenging field, offering a broader perspective for scientists across disciplines. Full article
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