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Mental Disorder: Focus on Pathogenesis to Treatment
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Mental Disorder: Focus on Pathogenesis to Treatment

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 1951

Special Issue Editor

Dr. Carmen Concerto

E-Mail Website
Guest Editor
Psychiatry Unit, Policlinico University Hospital "G. Rodolico-San Marco", Catania, Italy
Interests: complementary alternative medicine; neuroplasticity; non invasive brain stimulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The etiology of mental disorders is multifactorial, involving a complex interplay of genetic, neurobiological, environmental, and psychological factors. Previous studies have identified numerous risk-conferring gene variants and polygenic risk scores associated with neurodevelopmental, neurotransmitter, and synaptic pathways. Neurobiological factors include dysregulations in neurotransmitter systems, structural/functional brain abnormalities, and neuroendocrine disturbances. Neuroimaging techniques have revealed alterations in regions like the prefrontal cortex, hippocampus, and amygdala. Prenatal insults, childhood adversity, stressful life events, and socioeconomic disadvantages increase vulnerability through mechanisms such as hypothalamic–pituitary–adrenal axis dysfunction, inflammation, and oxidative stress. Psychological factors like maladaptive coping strategies and personality traits modulate illness trajectories. Environmental exposures like toxins further exacerbate risk. Elucidating these complex pathways is crucial for developing personalized prevention, diagnostic, and therapeutic strategies tailored to individual risk profiles.

Dr. Carmen Concerto
Guest Editor

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Keywords

  • mental disorders
  • neurobiological
  • oxidative stress
  • neuroinflammation
  • gene variants

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Published Papers (4 papers)

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Research

32 pages, 1766 KiB  
Article
Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation
by Yan Zhao, Zhuoming Zhao, Qianqian Sun, Hang Su, Tianzhen Chen, Xiaomin Xu, Xiaotong Li, Sai Shi, Jiang Du, Haifeng Jiang and Min Zhao
Curr. Issues Mol. Biol. 2025, 47(7), 479; https://doi.org/10.3390/cimb47070479 - 20 Jun 2025
Abstract
The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed [...] Read more.
The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway. Full article
(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)
16 pages, 865 KiB  
Article
Association of TNF-α and IL-6 Concentrations with Depression in Patients with Rheumatoid Arthritis
by Jelena Mrđa, Ljiljana Tadić-Latinović, Ljubinka Božić Majstorović, Vladimir Mrđa, Bosa Mirjanić-Azarić, Irma Ovčina, Semir Vranić and Snježana Popović-Pejičić
Curr. Issues Mol. Biol. 2025, 47(6), 419; https://doi.org/10.3390/cimb47060419 - 5 Jun 2025
Viewed by 355
Abstract
Background/Aim: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, characterized by the production of numerous pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which lead to pathophysiological changes in innate and acquired immunity. The existing evidence shows [...] Read more.
Background/Aim: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, characterized by the production of numerous pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), which lead to pathophysiological changes in innate and acquired immunity. The existing evidence shows that pro-inflammatory cytokines in rheumatoid arthritis impact monoaminergic neurotransmission, neurotropic factors, and synaptic activity, which may lead to the development of depression. Materials and Methods: In our study, we explored the association between TNF-α and IL-6, disease activity, and the degree of depression in patients with RA. The association between TNF-α and IL-6 and the Beck and Hamilton depression scales was analyzed in a group of 116 RA patients with depression. We investigated the same correlation in 45 patients with primary depression who represented the control group. Results: A Spearman test showed that IL-6 levels had a positive association with the Beck and Hamilton scales (p < 0.05) and that TNF-α had a positive association with the Hamilton scale (p < 0.05). Also, the Hamilton depression scale was the more sensitive scale in the detection of depressive symptoms. Conclusions: Our study indicates that elevated values of pro-inflammatory cytokines are associated with the degree of depression in patients with RA. Future preclinical and clinical studies will contribute to a better understanding of the pathophysiological mechanism of depression in patients with RA and may serve as the basis for new treatment modalities. By detecting depression promptly, with the help of the HAM-D as the more sensitive scale, we could influence the future modality of treatment, and with a multidisciplinary approach, we could ensure an improvement in the quality of life of patients with RA. Full article
(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)
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15 pages, 4488 KiB  
Article
Exploration of the Mechanisms of Acorus tatarinowii in the Treatment of Major Depressive Disorder Based on Network Pharmacology and Molecular Docking Techniques
by Li Han, Siwen Wei, Rong Wang, Yiran Liu, Yi Zhong and Huaiqing Luo
Curr. Issues Mol. Biol. 2025, 47(5), 342; https://doi.org/10.3390/cimb47050342 - 9 May 2025
Viewed by 449
Abstract
Objective: To elucidate the molecular targets and mechanisms by which Acorus tatarinowii exerts therapeutic effects in major depressive disorder (MDD) using network pharmacology and molecular docking approaches. Methods: Bioactive compounds of Acorus tatarinowii were identified from comprehensive pharmacological databases. MDD-related targets were sourced [...] Read more.
Objective: To elucidate the molecular targets and mechanisms by which Acorus tatarinowii exerts therapeutic effects in major depressive disorder (MDD) using network pharmacology and molecular docking approaches. Methods: Bioactive compounds of Acorus tatarinowii were identified from comprehensive pharmacological databases. MDD-related targets were sourced from extensive genomic repositories. Overlapping targets were determined and subjected to network topology and protein–protein interaction (PPI) analyses to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal pertinent biological processes and signaling pathways. Molecular docking simulations validated the interactions between key bioactive compounds and core targets. Results: A total of 57 bioactive compounds were identified in Acorus tatarinowii, including apigenin, heterotropan, and isoelemicin. Integrative analysis revealed 700 compound-related targets and 2590 MDD-associated targets, with 150 intersecting targets. Network analyses pinpointed five core targets: TP53, STAT3, AKT1, PIK3CA, and PIK3R1. GO enrichment identified 858 significant biological processes, while KEGG pathway analysis highlighted 155 enriched pathways, notably the PI3K-Akt, cAMP, and MAPK signaling pathways. Molecular docking studies demonstrated strong binding affinities between key compounds and their respective targets. Conclusions: This study delineates the multifaceted polypharmacological mechanisms through which Acorus tatarinowii may confer protective effects against major depressive disorder, underscoring its potential as a promising therapeutic agent. Full article
(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)
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14 pages, 274 KiB  
Article
A Comparison of the Treatment Effects of a Risperidone Solution, an Equal Ratio of DHA/ARA, and a Larger Ratio of Omega-6 PUFA Added to Omega-3 PUFA: An Open-Label Clinical Trial
by Kunio Yui and George Imataka
Curr. Issues Mol. Biol. 2025, 47(3), 184; https://doi.org/10.3390/cimb47030184 - 12 Mar 2025
Viewed by 673
Abstract
We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each [...] Read more.
We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each n = 13): RIS-OS; equal doses of 240 mg of omega-3 PUFA docosahexaenoic acid and omega-6 PUFA arachidonic acid (1:1) (aravita); and omega-6 precursor linoleic acid (480 mg) and omega-3 precursor alpha-linolenic acid (120 mg) (4:1) (awake). The primary outcome was the Autism Diagnostic Interview—Revised score. The secondary outcomes were the Social Responsiveness Scale (SRS) and Aberrant Behavior Check scores. The results of the linear mixed-effects model revealed that the RIS-OS group exhibited significant improvement in the SRS subscale scores of social motivation at weeks 8, 12, and 16 compared with the aravita and awake groups, as well as in the SRS subscale score of social mannerisms at weeks 12 and 16 compared with the aravita group. Moreover, the RIS-OS group showed a trend towards significantly lower plasma ceruloplasmin (Cp) levels. Their plasma insulin-like growth factor (IGF) levels were significantly higher at week 8 than in the subsequent weeks. The high Cp and IGF levels may be attributed to reduced neuroinflammation. These findings demonstrate, firstly, that reduced inflammation through increased anti-inflammatory proteins such as Cp and IGF has clinical effects on the motivation–reward system and mannerisms in patients with ASD through the amelioration of dopamine D2, 5-HT2a, and 5-HT2b dysfunction. Full article
(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)
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