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Mental Disorders and Translational Psychiatry: From Neurobiology to Therapeutic Perspective

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 9761

Special Issue Editors


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Guest Editor
1. Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
2. Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: biochemistry; clinical biochemistry; biomarkers of disease; biomarkers of mental disorders

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Guest Editor
Department of Mental Health and Addiction, Azienda Usl Toscana-Centro, 50134 Florence, Italy
Interests: clinical psychiatry; biochemistry; biomarkers of mental disorders

Special Issue Information

Dear Colleagues,

Mental disorders exert a huge burden on global human health and healthcare programs. Recent epidemiological data from health organizations report that about 40–50% of people worldwide may develop mental distress in their lifetime. Furthermore, mental disorders in their full-blown and severe forms can lead to inadequate lifestyles, high disability, social isolation and even discrimination, causing a reduction in life expectancy, and serious damage to those affected, to their family and, ultimately, to the entire community.

As a matter of fact, one of the main characteristics of psychiatric conditions is their prominent heterogeneity in the presentation of symptoms, as well as their tendency to become chronic and relapse from therapies. A consequent and increasingly emergent feature of mental diseases is also related to the frequent description of psychiatric comorbidity, or the presence in a single patient of more than one disorder. Additionally, mental illness may considerably increase vulnerability to somatic disorders such as diabetes, cardiovascular diseases, obesity, autoimmune and/or inflammatory diseases, as well as, in some cases, to neurodegeneration. Based on these assumptions, the urgency and usefulness of identifying potential risk factors that can explain how and when these highly disabling conditions can arise and/or negatively progress is topical, especially for developing ever-more targeted, tailored and refined therapeutic interventions. In the attempt to reach these aims, unraveling the neurobiological bases of mental disorders is fundamental. The development of neuroscience research in this field and the evolution of psychiatric diagnostic criteria, extending to the formulation of the concept of mental spectrum disorder, have suggested that these disabilities can derive from a variable gene as defined through genomic studies. These investigations have often revealed common polygenic correlates and genetic variants impacting human behavioral traits. Evidence has also shown that mental disorders may underlie dysfunctional neural circuits and molecular and metabolic alterations in the brain. Such variations involve not only the originally identified monoamine neurotransmission impairment, but also, to changing degrees, other interacting neurotransmitter systems such as the glutamate/GABA circuitries, catecholamine-related signaling, the activity of endocannabinoid-sensitive synapses, neuromodulators as neuropeptides and neurotrophins, neuroendocrine axes of stress adaptation/resilience (allostatic response), danger (damage)- associated molecular patterns (DAMPS), immunity, inflammasomes, purinergic and amino acid metabolism/sensing and mitochondrial functions, as well as epigenetic modifications, RNA transcriptomics, metabotropic/ionotropic receptor signal paths, protein kinases/phosphatase regulation and redox-buffer reactions. Even if it appears still premature to attest to the precise cause–effect relationships between these molecular patterns in the pathogenesis of mental disorders, the detection of neuroendocrine imbalance and a dysregulated brain-to-periphery communication in patients suffering from a specific mental disorder is thought to reveal their molecular signatures and vulnerabilities, following an integrated vision of disease. Under this prism, the present Special Issue will consider full-research articles, narrative or systematic reviews and metanalyses focused on new findings in the search of neurobiological alterations of mental diseases, as well as the detection of peripheral biomarkers in translational psychiatry, with particular reference to mood disorders (depressive disorders; bipolar Disorders), psychotic disorders, autism spectrum disorders (ASD) and post-traumatic stress disorder (PTSD), by highlighting aspects linked to phenotypic heterogeneity, psychiatric and somatic comorbidities, lifestyle and nutritional aspects, resistance to pharmacological treatment and therapeutic perspectives.

This special issue is led by Dr. Lionella Palego, Dr. Valerio Dell’Oste and assisted by our Topical Advisory Panel Member Dr. Kristina Mlinac-Jerković (University of Zagreb).

Dr. Lionella Palego
Dr. Valerio Dell’Oste
Guest Editors

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Keywords

  • mental disorders
  • illness heterogeneity
  • comorbidity
  • treatment resistance
  • neurobiology
  • applied neuroscience
  • translational psychiatry
  • peripheral biomarkers

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Published Papers (4 papers)

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Research

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18 pages, 2067 KiB  
Article
Plasma and Platelet Brain-Derived Neurotrophic Factor (BDNF) Levels in Bipolar Disorder Patients with Post-Traumatic Stress Disorder (PTSD) or in a Major Depressive Episode Compared to Healthy Controls
by Valerio Dell’Oste, Lionella Palego, Laura Betti, Sara Fantasia, Davide Gravina, Andrea Bordacchini, Virginia Pedrinelli, Gino Giannaccini and Claudia Carmassi
Int. J. Mol. Sci. 2024, 25(6), 3529; https://doi.org/10.3390/ijms25063529 - 20 Mar 2024
Cited by 3 | Viewed by 2175
Abstract
Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study [...] Read more.
Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD (n = 20) or in a major depressive episode (n = 20) were rigorously recruited together with unrelated healthy controls (n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets’ role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients. Full article
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36 pages, 1094 KiB  
Review
Changes in Concentration of Selected Biomarkers of Exposure in Users of Classic Cigarettes, E-Cigarettes, and Heated Tobacco Products—A Narrative Review
by Justyna Śniadach, Aleksandra Kicman, Anna Michalska-Falkowska, Kamila Jończyk and Napoleon Waszkiewicz
Int. J. Mol. Sci. 2025, 26(5), 1796; https://doi.org/10.3390/ijms26051796 - 20 Feb 2025
Viewed by 1105
Abstract
Currently, the number of e-cigarette and heated tobacco product (HTP) users are steadily increasing, while the number of classic cigarette users are decreasing. The effects of smoking classic cigarettes on human health have been thoroughly described in the literature, but the negative health [...] Read more.
Currently, the number of e-cigarette and heated tobacco product (HTP) users are steadily increasing, while the number of classic cigarette users are decreasing. The effects of smoking classic cigarettes on human health have been thoroughly described in the literature, but the negative health effects of e-cigarettes and HTPs on the human body are not clearly defined. Among users of different forms of tobacco, those at a particularly high risk of developing particular disease entities should be identified, allowing for the faster implementation of potential treatments, including psychotherapeutic ones. Biomarkers are used for this purpose. This paper summarizes the potential of these compounds from the different exposure groups of classic cigarettes, e-cigarettes, and HTPs, and presents changes in their concentrations in the body fluids of different tobacco users. This review discusses the impact of tobacco use in relation to levels of the following biomarkers: TNF-α, IL-1β, IL-6, IL-8, IL-17, IFN-γ, IL-10, IL-4, Il-13, TGF-β, VEGF EGF, HGF, BDNF, MMP-9, CRP, microplastics, and selected parameters of oxidative stress. This review also includes suggested forms of treatment, including Tobacco Product Use Reduction Programs, to minimize the potential negative effects of the above-mentioned products. Full article
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21 pages, 1495 KiB  
Review
Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder
by Borna Puljko, Marija Štracak, Svjetlana Kalanj-Bognar, Ivana Todorić Laidlaw and Kristina Mlinac-Jerkovic
Int. J. Mol. Sci. 2025, 26(3), 1322; https://doi.org/10.3390/ijms26031322 - 4 Feb 2025
Viewed by 1166
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation. Diagnosing ASD is complex, and the criteria for diagnosis, as well as the term ASD, have changed during the last decades. Diagnosis is made based on observation and accomplishment of specific [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation. Diagnosing ASD is complex, and the criteria for diagnosis, as well as the term ASD, have changed during the last decades. Diagnosis is made based on observation and accomplishment of specific diagnostic criteria, while a particular biomarker of ASD does not yet exist. However, studies universally report a disequilibrium in membrane lipid content, pointing to a unique neurolipid signature of ASD. This review sheds light on the possible role of cholesterol and gangliosides, complex membrane glycosphingolipids, in the development of ASD. In addition to maintaining membrane integrity, neuronal signaling, and synaptic plasticity, these lipids play a role in neurotransmitter release and calcium signaling. Evidence linking ASD to lipidome changes includes low cholesterol levels, unusual ganglioside levels, and unique metabolic profiles. ASD symptoms may be mitigated with therapeutic interventions targeting the lipid composition of membranes. However, restoring membrane equilibrium in the central nervous system remains a challenge. This review underscores the need for comprehensive research into lipid metabolism to uncover practical insights into ASD etiology and treatment as lipidomics emerges as a major area in ASD research. Full article
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22 pages, 1128 KiB  
Review
Insights into the Medical Evaluation of Ekbom Syndrome: An Overview
by Florina Madalina Mindru, Andrei-Flavius Radu, Adrian Gheorghe Bumbu, Ada Radu and Simona Gabriela Bungau
Int. J. Mol. Sci. 2024, 25(4), 2151; https://doi.org/10.3390/ijms25042151 - 10 Feb 2024
Cited by 4 | Viewed by 4542
Abstract
Ekbom syndrome, also known as delusional parasitosis (DP) or delusional infestation, is an uncommon psychiatric disorder distinguished by an enduring conviction of parasitic infestation, persisting notwithstanding the presence of medical evidence to the contrary. Primarily affecting middle-aged women, DP can manifest either as [...] Read more.
Ekbom syndrome, also known as delusional parasitosis (DP) or delusional infestation, is an uncommon psychiatric disorder distinguished by an enduring conviction of parasitic infestation, persisting notwithstanding the presence of medical evidence to the contrary. Primarily affecting middle-aged women, DP can manifest either as isolated psychological distress or as a component within a more intricate psychiatric framework, substantially influencing the quality of life for affected individuals. Its pathophysiological mechanism involves uncertain dopaminergic imbalances and dysfunction in the dopamine transporter system. Dermatologists often play a pivotal role in diagnosis, as patients first seek dermatological assessments of their signs and symptoms. However, DP frequently originates from underlying psychiatric disorders or medical variables, manifesting with neurological and infectious causative factors. The diagnostic complexity is attributed to patients’ resolute convictions, leading to delayed psychiatric intervention. First-line DP treatment involves antipsychotics, with newer agents demonstrating promising prospects, but the lack of standardized protocols poses a significant therapeutic challenge. In this narrative review, both a comprehensive approach to this uncommon pathology and an update on the state of knowledge in this medical subfield focused on optimizing the management of DP are provided. The complexity of DP underlying its uncommon nature and the incomplete understanding of its pathophysiology highlight the need for further research through multicenter studies and multidisciplinary teams to enhance therapeutic efficacy and safety. Full article
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