Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 8039

Special Issue Editors


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Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; cannabinoids
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Interests: pharmacology; pharmacodynamics; neuroscience; preclinical studies; mood disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Mental disorders are a major public health concern and a leading contributor to the global disease burden. There are many limitations of ongoing pharmacotherapy, especially in severe mental disorders such as affective disorders (depression, bipolar disorder, and anxiety disorders) and schizophrenia. The complex pathomechanisms of these mental disorders imply that medication responses vary across patients. The importance of the problem of mental illnesses is also emphasized by the fact of their co-occurrence, which significantly hinders proper treatment. This is why it is so important to know the pathomechanisms associated with these diseases. Depression and schizophrenia represent some of the most prevalent and highly comorbid psychiatric conditions; thus, increased effective therapeutic attention to both symptoms—mood and psychosis—is needed to improve outcomes and support prevention. Currently, the use of antipsychotic drugs, as monotherapy or as adjuncts to antidepressants and mood-stabilizing medicines, is also common practice for mood disorders that are not necessarily associated with psychosis. Furthermore, the use of many antipsychotic drugs carries a risk of serious adverse effects that may not only significantly affect a patient's quality of life but also shorten its duration. These problems are indications of the need to search for new treatments for mental diseases that are characterized by beneficial pharmacological effects and suitable safety profile actions.

Thus, this Special Issue aims to address the pressing need for the development of new drugs to treat affective disorders and/or schizophrenia. The aim of this project is to bring together international experts to provide a comprehensive overview of this research field. Therefore, I invite you to participate with either an original article or a review focused on some aspects of the subject.

Dr. Jolanta Orzelska-Górka
Dr. Marta Kruk-Słomka
Dr. Ewa Kędzierska
Dr. Ewa Gibuła-Tarłowska
Guest Editors

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Keywords

  • depression
  • anxiety
  • bipolar disorders
  • schizophrenia
  • mental disorders

Published Papers (5 papers)

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Research

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15 pages, 2507 KiB  
Article
Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression
by Veronika Kovacova, Andrea Macejova, Ingrid Tonhajzerova, Zuzana Visnovcova, Nikola Ferencova, Zuzana Mlyncekova, Tomas Kukucka, Ivan Farsky, Slavomir Nosal and Igor Ondrejka
Pharmaceuticals 2024, 17(3), 358; https://doi.org/10.3390/ph17030358 - 10 Mar 2024
Viewed by 767
Abstract
Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal [...] Read more.
Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1–10, total score), and CDI (items A–E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD. Full article
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14 pages, 1823 KiB  
Article
Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study
by Jia-Ru Li, Ling-Ling Yeh, Ji-Yu Lin and Yi-Ju Pan
Pharmaceuticals 2024, 17(1), 78; https://doi.org/10.3390/ph17010078 - 08 Jan 2024
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Abstract
As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative [...] Read more.
As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the ‘no exposure’ category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS. Full article
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15 pages, 323 KiB  
Article
Biopsychosocial Variables in Male Schizophrenic Patients: A Comprehensive Comparison with Healthy Controls
by Krzysztof Krysta, Beata Trędzbor, Ewa Martyniak, Aleksandra Cieślik, Agnieszka Koźmin-Burzyńska, Katarzyna Piekarska-Bugiel, Katarzyna Skałacka, Rafał Bieś and Marek Krzystanek
Pharmaceuticals 2023, 16(12), 1633; https://doi.org/10.3390/ph16121633 - 21 Nov 2023
Viewed by 1040
Abstract
Objective: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). Methods: participants underwent a battery of neuropsychological tests including the Trail [...] Read more.
Objective: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). Methods: participants underwent a battery of neuropsychological tests including the Trail Making Test (TMT), Stroop Color-Word Interference Test, and Verbal Fluency Test. Psychopathological symptoms in the SZ group were evaluated using the Positive and Negative Syndrome Scale (PANSS). Anthropometric measurements such as body weight, height, BMI, and waist circumference were taken. Biochemical markers measured included fasting glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and fasting insulin. Lifestyle factors were assessed through a questionnaire for the study of views and eating habits of people aged 16 to 65. Results: the HC group outperformed the SZ group in the TMT_A test and the Stroop test, but no significant differences were observed in the TMT_B test or in phonemic fluency tests. No correlation was found between age and PANSS scores within the SZ group. Anthropometrically, the SZ group had higher body weight, waist circumference, and BMI, with no difference in height. Biochemically, the HC group had higher HDL cholesterol levels but lower insulin and insulin resistance indices. Pharmacological assessment showed a more significant impact on body weight among SZ patients taking second-generation antipsychotics. Lifestyle factors such as diet and screen time were comparable between groups, but the SZ group reported longer sleep duration and lower leisure time activity. Conclusions: our study highlights distinct neuropsychological, pharmacological, anthropometric, and biochemical differences between male schizophrenic patients and healthy controls. The results underscore the complexity of schizophrenia and point toward the need for a multi-faceted approach to its management and understanding. Full article

Review

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11 pages, 1764 KiB  
Review
Involvement of the Expression of G Protein-Coupled Receptors in Schizophrenia
by Raluka Kalinovic, Andrei Pascariu, Gabriela Vlad, Diana Nitusca, Andreea Sălcudean, Ioan Ovidiu Sirbu, Catalin Marian and Virgil Radu Enatescu
Pharmaceuticals 2024, 17(1), 85; https://doi.org/10.3390/ph17010085 - 09 Jan 2024
Cited by 1 | Viewed by 971
Abstract
The expression of GPCRs has been associated with schizophrenia, and their expression may induce morphological changes in brain regions responsible for schizophrenia and disease-specific behavioral changes. The articles included in this review were selected using keywords and databases of scientific research websites. The [...] Read more.
The expression of GPCRs has been associated with schizophrenia, and their expression may induce morphological changes in brain regions responsible for schizophrenia and disease-specific behavioral changes. The articles included in this review were selected using keywords and databases of scientific research websites. The expressions of GPRs have different involvements in schizophrenia, some increase the risk while others provide protection, and they may also be potential targets for new treatments. Proper evaluation of these factors is essential to have a better therapeutic response with a lower rate of chronicity and thus improve the long-term prognosis. Full article
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23 pages, 1322 KiB  
Review
Research in the Field of Drug Design and Development
by Grazyna Biala, Ewa Kedzierska, Marta Kruk-Slomka, Jolanta Orzelska-Gorka, Sara Hmaidan, Aleksandra Skrok, Jakub Kaminski, Eva Havrankova, Dominika Nadaska and Ivan Malik
Pharmaceuticals 2023, 16(9), 1283; https://doi.org/10.3390/ph16091283 - 11 Sep 2023
Cited by 4 | Viewed by 3693
Abstract
The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and [...] Read more.
The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and well-tolerated compounds, as well as the ineffectiveness of existing therapies, and society’s insufficient knowledge concerning the prophylactics and pharmacotherapy of the most common diseases today, comprise a serious challenge. This can influence not only the quality of human life, but also the health of whole societies, which became evident during the COVID-19 pandemic. In general, the process of drug development consists of three main stages: drug discovery, preclinical development using cell-based and animal models/tests, clinical trials on humans and, finally, forward moving toward the step of obtaining regulatory approval, in order to market the potential drug. In this review, we will attempt to outline the first three most important consecutive phases in drug design and development, based on the experience of three cooperating and complementary academic centers of the Visegrád group; i.e., Medical University of Lublin, Poland, Masaryk University of Brno, Czech Republic, and Comenius University Bratislava, Slovak Republic. Full article
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