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

Deadline for manuscript submissions: closed (5 February 2023) | Viewed by 48109

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Special Issue Editors

Dr. Marcin Siwek

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Guest Editor

Department of Affective Disorders, Jagiellonian University Medical College, Krakow, Poland
Interests: clinical psychopharmacology; clinical psychiatry; psychopharmacotherapy; drug interactions; drug resistant depression; bipolar disorder; laboratory markers of affective disorders and schizophrenia; neuropsychiatry; fibromyalgia

Dr. Adrian Andrzej Chrobak

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Guest Editor

Department of Adult Psychiatry, Jagiellonian University Medical College, Kraków, Poland
Interests: clinical psychopharmacology; clinical psychiatry; psychopharmacotherapy; drug in-teractions; drug resistant depression; bipolar disorder; schizophrenia; neuropsychia-try; chronobiology

Dr. Bernadeta Szewczyk

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Guest Editor

Maj Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
Interests: neuropsychopharmacology; psychiatric disorders; neurobiology; drug interactions; biomarkers of psychiatric disorders; biometals; receptors; cell signaling

Special Issue Information

Dear Colleagues,

Psychotic disorders (including schizophrenia and schizophrenia-related disorders) cover a wide group of mental illnesses, with a total incidence rate estimated at approximately 4/1000/year. Due to the significant heterogeneity, research into the biological mechanisms of these disorders is a huge challenge, and we are far from understanding their detailed etiology and pathophysiology. While there is significant progress in the field of psychopharmacotherapy, still, only about half of patients with a diagnosis of schizophrenia achieve symptomatic remission, and only a quarter of them have adequate social functioning after a long period of treatment. In addition, approximately one-third of patients are drug-resistant. A significant problem in the pharmacotherapy of psychoses is their multidimensional nature (the need to simultaneously influence positive, negative, and affective symptoms, as well as cognitive and behavioral disorders), treatment nonadherence, side effects of antipsychotic drugs, somatic consequences of their use and general medical comorbidity. In this Special Issue, our aim will be to focus on the challenges of psychopharmacology and biological studies of psychosis.

Dr. Marcin Siwek
Dr. Adrian Andrzej Chrobak
Dr. Bernadeta Szewczyk
Guest Editors

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Keywords

psychosis
schizophrenia
antipsychotics
drug interactions
pathophysiology
treatment-resistance
functional recovery
negative symptoms
positive symptoms
cognitive impairment

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Published Papers (13 papers)

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Editorial

Jump to: Research, Review

3 pages, 190 KiB

Open AccessEditorial

Psychopharmacology and Biological Studies of Psychosis

by Marcin Siwek, Bernadeta Szewczyk and Adrian Andrzej Chrobak

Brain Sci. 2023, 13(6), 854; https://doi.org/10.3390/brainsci13060854 - 25 May 2023

Cited by 1 | Viewed by 1304

Abstract

In most cases, psychotic episodes occur in the course of chronic mental illnesses, e [...] Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

Research

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18 pages, 351 KiB

Open AccessEditor’s ChoiceArticle

Oxidative Stress Biomarkers among Schizophrenia Inpatients

by Magdalena Więdłocha, Natalia Zborowska, Piotr Marcinowicz, Weronika Dębowska, Marta Dębowska, Anna Zalewska, Mateusz Maciejczyk, Napoleon Waszkiewicz and Agata Szulc

Brain Sci. 2023, 13(3), 490; https://doi.org/10.3390/brainsci13030490 - 14 Mar 2023

Cited by 14 | Viewed by 2347

Abstract

Background. Finding the associations between schizophrenia symptoms and the biomarkers of inflammation, oxidative stress and the kynurenine pathway may lead to the individualization of treatment and increase its effectiveness. Methods. The study group included 82 schizophrenia inpatients. The Positive and Negative Symptoms Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS) and the Calgary Depression in Schizophrenia Scale were used for symptom evaluation. Biochemical analyses included oxidative stress parameters and brain-derived neurotrophic factor (BDNF). Results. Linear models revealed the following: (1) malondiadehyde (MDA), N-formylkynurenine (N-formKYN), advanced oxidation protein products (AOPP), advanced glycation end-products of proteins (AGE) and total oxidative status (TOS) levels are related to the PANSS-total score; (2) MDA, reduced glutathione (GSH) and BDNF levels are related to the PANSS-negative score; (3) TOS and kynurenine (KYN) levels are related to the PANSS-positive score; (4) levels of total antioxidant status (TAS) and AOPP along with the CDSS score are related to the BACS-total score; (5) TAS and N-formKYN levels are related to the BACS-working memory score. Conclusions. Oxidative stress biomarkers may be associated with the severity of schizophrenia symptoms in positive, negative and cognitive dimensions. The identification of biochemical markers associated with the specific symptom clusters may increase the understanding of biochemical profiles in schizophrenia patients. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

12 pages, 1206 KiB

Open AccessArticle

Lurasidone Augmentation of Clozapine in Schizophrenia—Retrospective Chart Review

by Marcin Siwek, Adrian Andrzej Chrobak, Aleksandra Gorostowicz, Patrycja Król and Dominika Dudek

Brain Sci. 2023, 13(3), 445; https://doi.org/10.3390/brainsci13030445 - 4 Mar 2023

Cited by 4 | Viewed by 3068

Abstract

The aim of our study was to evaluate the effectiveness of lurasidone augmentation of clozapine in treatment-resistant schizophrenia (SZ) in a retrospective chart review. From the medical records of 916 SZ patients, we identified 16 individuals treated with a combination of clozapine and lurasidone. The detailed clinical data are described separately for each patient. We compared the Clinical Global Impression—Severity (CGI-S) scores between three points of observation: before the treatment and one month and two months after its initiation. CGI Improvement (CGI-I) scores were used to evaluate the treatment response between the first and last points of observation. The vast majority of patients (14/16, 87.5%) responded to lurasidone augmentation of clozapine (CGI-I scores 1 or 2). Therapeutic effects were observable after 3–12 weeks of treatment (median 6 (4–6)). A reduction in CGI-S scores was observed after the first month of observation. There was an observable reduction in positive, depressive and anxiety symptoms, as well as an improvement in psychosocial functioning. Two patients discontinued treatment due to side effects. Our study suggests that lurasidone augmentation of clozapine may lead to improvements in a broad range of SZ symptom dimensions. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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22 pages, 3566 KiB

Open AccessArticle

A Comparative Study of the Impact of NO-Related Agents on MK-801- or Scopolamine-Induced Cognitive Impairments in the Morris Water Maze

by Paulina Cieślik, Magdalena Borska and Joanna Monika Wierońska

Brain Sci. 2023, 13(3), 410; https://doi.org/10.3390/brainsci13030410 - 27 Feb 2023

Cited by 6 | Viewed by 2173

Abstract

Learning and memory deficits accompany numerous brain dysfunctions, including schizophrenia and Alzheimer’s disease (AD), and many studies point to the role of nitric oxide (NO) in these processes. The present investigations constitute the follow-up of our previous research, in which we investigated the activity of NO releasers and a selective inhibitor of neuronal NO synthase (nNOS) to prevent short-term memory deficits in novel object recognition and T-maze. Here, the ability of the compounds to prevent the induction of long-term memory deficits by MK-801 or scopolamine administration was investigated. The Morris Water Maze test, a reliable and valid test of spatial learning and memory, was used, in which escape latency in the acquisition phase and nine different parameters in the retention phase were measured. A fast NO releaser (spermine NONOate), a slow NO releaser (DETA NONOate), and a nNOS inhibitor, N(ω)-propyl-L-arginine (NPLA), were used. The compounds were administered i.p. at a dose range of 0.05–0.5 mg/kg. All compounds prevented learning deficits in the acquisition phase and reversed reference memory deficits in the retention phase of the scopolamine-treated mice. Spermine NONOate was the least effective. In contrast, the drugs poorly antagonised MK-801-induced deficits, and only the administration of DETA NONOate induced some improvements in the retention trial. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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9 pages, 265 KiB

Open AccessArticle

THINC-Integrated Tool (THINC-it): A Brief Measurement of Changes in Cognitive Functioning and Its Correlation with the Life Quality of Patients with Schizophrenia and Related Disorders—A Pilot Study

by Joanna K. Szmyd, Karol Lewczuk, Kayla M. Teopiz, Roger S. McIntyre and Adam Wichniak

Brain Sci. 2023, 13(3), 389; https://doi.org/10.3390/brainsci13030389 - 24 Feb 2023

Cited by 2 | Viewed by 2548

Abstract

Background: This pilot study aimed to assess patients’ cognitive functioning with the Polish version of the THINC-it tool and to analyze its association with self-reported quality of life (QOL). Methods: Twenty-one patients (mean age: 37.8 ± 10.4) were assessed at baseline and after six weeks of a standard therapeutic outpatient program. Participants completed the World Health Organization QOL Questionnaire (WHOQOL-BREF) and the THINC-it tool at both visits. The tool consists of tasks evaluating working memory (SYMBOL CHECK), attention (SPOTTER), executive functions (TRIALS), and cognitive skills (CODEBREAKER). Results: During the second visit, patients showed significant improvements in mean latency of correct responses of SPOTTER: p = 0.021, Cohen’s d = 0.38 and in the Physical health domain: p = 0.007, Cohen’s d = 0.37. The number of correct responses for CODEBREAKER was positively associated with the Physical health domain at visit 1 (r = 0.53, p = 0.014) and visit 2 (r = 0.42, p = 0.058). The number of correct responses at SYMBOL CHECK was positively related to QOL in the Environment domain only at visit 2 (r = 0.45, p = 0.042). Conclusions: These results suggest the THINC-it tool has utility as a cognitive measure in adults with schizophrenia in both clinical and research settings. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

14 pages, 849 KiB

Open AccessArticle

Benzodiazepines and Mood Stabilizers in Schizophrenia Patients Treated with Oral versus Long-Acting Injectable Antipsychotics—An Observational Study

by Ana Aliana Miron, Paula Simina Petric, Andreea Teodorescu, Petru Ifteni, Gabriela Chele and Andreea Silvana Szalontay

Brain Sci. 2023, 13(2), 173; https://doi.org/10.3390/brainsci13020173 - 20 Jan 2023

Cited by 4 | Viewed by 5170

Abstract

Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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9 pages, 238 KiB

Open AccessArticle

Ketamine as Add-On Treatment in Psychotic Treatment-Resistant Depression

by Maria Gałuszko-Węgielnik, Zuzanna Chmielewska, Katarzyna Jakuszkowiak-Wojten, Mariusz S. Wiglusz and Wiesław J. Cubała

Brain Sci. 2023, 13(1), 142; https://doi.org/10.3390/brainsci13010142 - 13 Jan 2023

Cited by 8 | Viewed by 5313

Abstract

Psychotic treatment-resistant depression is a complex and challenging manifestation of mood disorders in the clinical setting. Psychotic depression is a subtype of major depressive disorder characterized by mood-consistent hallucinations and/or delusions. Psychotic depression is often underdiagnosed and undertreated. Ketamine appears to have rapid and potent antidepressant effects in clinical studies, and the Federal Drug Agency approved the use of ketamine enantiomer esketamine-nasal spray for treatment-resistant depression pharmacotherapy in 2019. This study aimed to assess the usage of ketamine for major depressive disorder with psychotic features as an add-on treatment to the standard of care. Here we present four inpatients suffering from treatment-resistant depression with psychotic features, including one with severe suicidal crisis, all treated with 0.5 mg/kg intravenous infusion of ketamine. Subsequent monitoring revealed no exacerbation of psychotic symptoms in short and long-term observation, while stable remission was observed in all cases with imminent antisuicidal effect. Results suggest ketamine may benefit individuals with treatment-resistant depression with psychotic features. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

16 pages, 329 KiB

Open AccessArticle

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders

by Mirko Manchia, Ulker Isayeva, Roberto Collu, Diego Primavera, Luca Deriu, Edoardo Caboni, Maria Novella Iaselli, Davide Sundas, Massimo Tusconi, Federica Pinna, Pasquale Paribello, Maria Scherma, Claudia Pisanu, Anna Meloni, Clement C. Zai, Donatella Congiu, Alessio Squassina, Walter Fratta, Paola Fadda and Bernardo Carpiniello

Brain Sci. 2022, 12(12), 1666; https://doi.org/10.3390/brainsci12121666 - 4 Dec 2022

Cited by 13 | Viewed by 2755

Abstract

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

14 pages, 458 KiB

Open AccessArticle

Deficit Symptomatology of Schizophrenia Is Associated with Attenuated Taste Identification: Findings from a Cross-Sectional Study

by Michał Wroński, Jerzy Samochowiec, Justyna Pełka-Wysiecka, Paweł Liśkiewicz, Przemysław Bieńkowski and Błażej Misiak

Brain Sci. 2022, 12(11), 1520; https://doi.org/10.3390/brainsci12111520 - 9 Nov 2022

Cited by 2 | Viewed by 1963

Abstract

Schizophrenia is the subject of many studies. There have been reports of taste disturbances in mental disorders. We found a possible relationship between deficit symptoms of schizophrenia and the dysgeusia of monosodium glutamate (MSG). Dysgeusia is a disorder that distorts the sense of taste. People describe all foods as tasting sweet, sour, bitter, or metallic. We aimed to verify whether the level of MSG taste perception may be related to the severity of deficit symptoms. MSG detection threshold was assessed via sublingual administration of three fluid samples containing MSG or water. The MSG samples had different concentrations in each sample. The task was to indicate which of the samples contained MSG, determine the intensity of the taste, and assess the taste as pleasant, unpleasant, or neutral. The study group included 200 patients diagnosed with paranoid schizophrenia according to ICD-10. We found a significant negative correlation between mean intensity of taste and the number of deficit symptoms. The symptoms of taste disturbances reported by the patient should be monitored by clinicians and differentiated between the actual deficits in the field of taste perception and the taste hallucinations as a symptom of psychosis. It is important to continue research in this area. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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Review

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19 pages, 976 KiB

Open AccessReview

Exploring a Possible Interplay between Schizophrenia, Oxytocin, and Estrogens: A Narrative Review

by Danae Papadea, Christina Dalla and Despina A. Tata

Brain Sci. 2023, 13(3), 461; https://doi.org/10.3390/brainsci13030461 - 8 Mar 2023

Cited by 6 | Viewed by 4023

Abstract

Schizophrenia is characterized by symptoms of psychosis and sociocognitive deficits. Considering oxytocin’s antipsychotic and prosocial properties, numerous clinical, and preclinical studies have explored the neuropeptide’s therapeutic efficacy. Sex differences in the clinical course of schizophrenia, as well as in oxytocin-mediated behaviors, indicate the involvement of gonadal steroid hormones. The current narrative review aimed to explore empirical evidence on the interplay between schizophrenia psychopathology and oxytocin’s therapeutic potential in consideration of female gonadal steroid interactions, with a focus on estrogens. The review was conducted using the PubMed and PsychINFO databases and conforms to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. The results suggest a potential synergistic effect of the combined antipsychotic effect of oxytocin and neuroprotective effect of estrogen on schizophrenia. Consideration of typical menstrual cycle-related hormonal changes is warranted and further research is needed to confirm this assumption. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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21 pages, 383 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Targets in Schizophrenia Development and Therapy

by Agnieszka Wawrzczak-Bargieła, Wiktor Bilecki and Marzena Maćkowiak

Brain Sci. 2023, 13(3), 426; https://doi.org/10.3390/brainsci13030426 - 1 Mar 2023

Cited by 13 | Viewed by 5045

Abstract

Schizophrenia is regarded as a neurodevelopmental disorder with its course progressing throughout life. However, the aetiology and development of schizophrenia are still under investigation. Several data suggest that the dysfunction of epigenetic mechanisms is known to be involved in the pathomechanism of this mental disorder. The present article revised the epigenetic background of schizophrenia based on the data available in online databases (PubMed, Scopus). This paper focused on the role of epigenetic regulation, such as DNA methylation, histone modifications, and interference of non-coding RNAs, in schizophrenia development. The article also reviewed the available data related to epigenetic regulation that may modify the severity of the disease as a possible target for schizophrenia pharmacotherapy. Moreover, the effects of antipsychotics on epigenetic malfunction in schizophrenia are discussed based on preclinical and clinical results. The obtainable data suggest alterations of epigenetic regulation in schizophrenia. Moreover, they also showed the important role of epigenetic modifications in antipsychotic action. There is a need for more data to establish the role of epigenetic mechanisms in schizophrenia therapy. It would be of special interest to find and develop new targets for schizophrenia therapy because patients with schizophrenia could show little or no response to current pharmacotherapy and have treatment-resistant schizophrenia. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

14 pages, 312 KiB

Open AccessEditor’s ChoiceReview

Application of Antipsychotic Drugs in Mood Disorders

by Janusz K. Rybakowski

Brain Sci. 2023, 13(3), 414; https://doi.org/10.3390/brainsci13030414 - 27 Feb 2023

Cited by 14 | Viewed by 5407

Abstract

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

14 pages, 584 KiB

Open AccessEditor’s ChoiceReview

Brexpiprazole—Pharmacologic Properties and Use in Schizophrenia and Mood Disorders

by Marcin Siwek, Krzysztof Wojtasik-Bakalarz, Anna Julia Krupa and Adrian Andrzej Chrobak

Brain Sci. 2023, 13(3), 397; https://doi.org/10.3390/brainsci13030397 - 25 Feb 2023

Cited by 14 | Viewed by 5377

Abstract

In 2002, the first III generation antipsychotic drug was registered—aripiprazole. Its partial dopaminergic agonism underlies its unique mechanism of action and the potentially beneficial influence on the positive, negative, or cognitive symptoms. Due to its relatively high intrinsic activity, the drug could often cause agitation, anxiety, or akathisia. For this reason, efforts were made to develop a drug which would retain the positive favorable actions of aripiprazole but present a more advantageous clinical profile. This turned out to be brexpiprazole, which was registered in 2015. Its pharmacodynamic and pharmacokinetic profile (similarly to the other most recent antipsychotics, i.e., lurasidone or cariprazine) shows promise of increasing the effectiveness of schizophrenia treatment in the dimensions in which the previous antipsychotics were not sufficiently effective, including negative, depressive, or cognitive symptoms. Like other new antipsychotics, it can also be useful in the treatment of mood disorders, for instance drug-resistant depression. Previous reviews focused on the use of brexpiprazole in specific diagnostic groups. The aim of this article is to provide the readers with an overview of data on the mechanism of action, clinical effectiveness in all studied diagnostic groups, as well as potential drug–food interactions, and the safety of brexpiprazole. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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