Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders

A special issue of Healthcare (ISSN 2227-9032).

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 21749

Special Issue Editor


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Guest Editor
1. Department of Mental Health, Mutua Terrassa University Hospital, University of Barcelona, 08221 Terrassa, Spain
2. Neurosciences Institute, Universitat Autònoma de Barcelona, CIBERSAM, 08221 Terrassa, Spain
Interests: schizophrenia; psychosis; affective disorder; psychoneuroendocrinology
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Special Issue Information

Dear Colleagues,

For several decades, the dopamine hypothesis of schizophrenia has appeared to explain the neurobiology of the disorder, the biological underpinnings of treatment response, and the main mechanism of action of antipsychotic responses. However, a high amount of research points to the implication of other biological and neurotransmitter systems. Patients with schizophrenia exhibit marked positive and negative symptoms, as well as present cognitive symptoms and affective domains. Although antipsychotics are considered the gold standard, preclinical and clinical studies report that almost one-third of patients with schizophrenia fail to respond to standard antipsychotic treatment.

The present Special Issue aims to summarize new evidence on the role of biological systems interacting with dopamine and other neurotransmitters implicated in the occurrence of psychotic symptoms and treatment responses. The role of stress hormones and other hormonals compounds in the clinical presentation (phenotype) and response to treatment will also be explored. Evidence for the effectiveness of pharmacological and non-pharmacological interventions to treat schizophrenia and related disorders is also welcome, with a special emphasis on treatments targeting emotions and cognitive symptoms. The impact of physical health on psychotic symptoms and vice versa is also a topic of interest in psychotic populations.

Dr. Jose Antonio Monreal
Guest Editor

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Keywords

  • psychosis
  • neurobiology
  • clinical phenotypes
  • treatment outcomes

Published Papers (10 papers)

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Editorial

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2 pages, 189 KiB  
Editorial
Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders: New Challenges
by José Antonio Monreal and Alexandre González-Rodríguez
Healthcare 2022, 10(9), 1806; https://doi.org/10.3390/healthcare10091806 - 19 Sep 2022
Viewed by 1242
Abstract
For several decades, it has been postulated that dopaminergic pathways explain the neurobiology of schizophrenia, the biological underpinnings of treatment responses and the main mechanisms of action of antipsychotics [...] Full article

Research

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15 pages, 1054 KiB  
Article
A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences
by Marina Soler-Andrés, Alexandre Díaz-Pons, Víctor Ortiz-García de la Foz, Nancy Murillo-García, Sara Barrio-Martínez, Margarita Miguel-Corredera, Angel Yorca-Ruiz, Rebeca Magdaleno Herrero, Jorge Moya-Higueras, Esther Setién-Suero and Rosa Ayesa-Arriola
Healthcare 2023, 11(13), 1902; https://doi.org/10.3390/healthcare11131902 - 30 Jun 2023
Viewed by 1133
Abstract
Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a [...] Read more.
Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients’ cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors. Full article
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13 pages, 1940 KiB  
Article
Heterogeneity in Response to MCT and Psychoeducation: A Feasibility Study Using Latent Class Mixed Models in First-Episode Psychosis
by Marta Ferrer-Quintero, Daniel Fernández, Raquel López-Carrilero, Luciana Díaz-Cutraro, Marina Verdaguer-Rodríguez, Helena García-Mieres, Elena Huerta-Ramos, Juana Gómez-Benito, Trini Peláez, Irene Birulés, Ana Barajas, Esther Pousa, Marisa Barrigón, Alfonso Gutiérrez-Zotes, Eva Grasa, Isabel Ruiz-Delgado, Esther Lorente-Rovira, Jordi Cid, on behalf of the Spanish Metacognition Study Group and Susana Ochoa
Healthcare 2022, 10(11), 2155; https://doi.org/10.3390/healthcare10112155 - 28 Oct 2022
Viewed by 1584
Abstract
Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models [...] Read more.
Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatments. Full article
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Review

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11 pages, 839 KiB  
Review
Systematic Review of the Apomorphine Challenge Test in the Assessment of Dopaminergic Activity in Schizophrenia
by Fabrice Duval
Healthcare 2023, 11(10), 1487; https://doi.org/10.3390/healthcare11101487 - 19 May 2023
Viewed by 986
Abstract
So far, neuroendocrine studies conducted in schizophrenic patients have yielded conflicting results. Many of these discrepancies may be explained by the diversity of factors that influence the hormonal levels (at baseline and in response to pharmacological stimuli), the heterogeneity of the populations studied, [...] Read more.
So far, neuroendocrine studies conducted in schizophrenic patients have yielded conflicting results. Many of these discrepancies may be explained by the diversity of factors that influence the hormonal levels (at baseline and in response to pharmacological stimuli), the heterogeneity of the populations studied, the absence of standardization of test challenges and the confounding and long-lasting effects of previous treatments. Numerous studies have used apomorphine (APO) in the evaluation of dopaminergic (DA) function in schizophrenic patients. APO, a direct acting DA receptor agonist, decreases prolactin (PRL) and stimulates growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion. Therefore, the magnitude of hormonal responses to APO is an indirect assessment of the functionality of DA receptors at the hypothalamic–pituitary level. This review provides an update on the applications of the APO test in schizophrenia in clinical, pathophysiological and therapeutic fields. Full article
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31 pages, 871 KiB  
Review
Neurological Soft Signs in Schizophrenia, a Picture of the Knowledge in the Last Decade: A Scoping Review
by Cristian Petrescu, Diana M. Petrescu, Gabriela Marian, Brindusa E. Focseneanu, Floris Petru Iliuta, Constantin Alexandru Ciobanu, Serban Papacocea and Adela M. Ciobanu
Healthcare 2023, 11(10), 1471; https://doi.org/10.3390/healthcare11101471 - 18 May 2023
Cited by 3 | Viewed by 1735
Abstract
(1) Background: Neurological Soft Signs (NSS) are subtle neurological abnormalities that are more common in schizophrenia patients than in healthy individuals and have been regularly observed in neuroleptic-naive first-episode patients, supporting the hypothesis that they are an intrinsic component of schizophrenia. (2) Methods: [...] Read more.
(1) Background: Neurological Soft Signs (NSS) are subtle neurological abnormalities that are more common in schizophrenia patients than in healthy individuals and have been regularly observed in neuroleptic-naive first-episode patients, supporting the hypothesis that they are an intrinsic component of schizophrenia. (2) Methods: a review of articles published in the last ten years (from January 2013 to January 2023) was carried out on articles published in ScienceDirect and PubMed, by following the PRISMA Statement extension for scoping reviews (PRISMA-ScR), which evaluated the impact of NSS in correlation with the symptomatology, neuroleptic treatment, and the cerebral structural changes of patients with schizophrenia. (3) Results: thirty articles were included, among them twelve included MRI structural evaluation and four studies with a longitudinal design. (4) Conclusions: interest in researching NSS has increased in recent years, but questions remain about their origin and relationship to schizophrenia symptoms, thus this study aims to fill in information gaps in the hope that future research will help provide individualized treatment. It is suggested that NSS in schizophrenia might have an inherited genetic relationship pattern, thus being in line with a trait viewpoint. Most of the research revealed that schizophrenia patients had higher NSS scores than healthy controls, however, they were rather similar to their first-degree relatives, thus, also arguing in favor of a trait perspective. The greatest improvement in scores is seen in those with a remitting course, as shown by declining NSS ratings concurrent with symptomatology. Full article
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11 pages, 279 KiB  
Review
Critical Issues in the Management of Agitation, Aggression, and End-of-Life in Delusional Disorder: A Mini-Review
by Alexandre González-Rodríguez, Mary V. Seeman, Eloïsa Román, Mentxu Natividad, Carmen Pagés, Camila Ghigliazza, Laura Ros and José A. Monreal
Healthcare 2023, 11(4), 458; https://doi.org/10.3390/healthcare11040458 - 05 Feb 2023
Viewed by 1772
Abstract
Background: Compared to other psychotic disorders, there is little information about staging care in delusional disorder (DD). Unlike schizophrenia, this is a disorder that begins in middle age, a time at which chronic medical comorbidities have already begun to impact global functioning. [...] Read more.
Background: Compared to other psychotic disorders, there is little information about staging care in delusional disorder (DD). Unlike schizophrenia, this is a disorder that begins in middle age, a time at which chronic medical comorbidities have already begun to impact global functioning. With age, the combination of psychological and somatic conditions leads to new behaviours, e.g., agitation, aggression, and behaviours that require specific preventive and interventive measures. With further age, knowledgeable end-of-life care becomes necessary for this population. Aim: The aim of this article was to review existing evidence on the management of these successive phases. Methods: We conducted a narrative review using PubMed and ClinicalTrials.gov and searched for the following terms: (agitation OR aggressivity OR aggression OR palliative OR “end-of-life”) AND (“delusional disorder”). Results: We found that the literature was sparse. Existing evidence suggests that medical causes are frequently at the root of agitation and aggression. With respect to management, de-escalation strategies are generally preferred over pharmacotherapy. Specific delusional syndromes, e.g., de Clérambault, Othello, Capgras, Fregoli, as well as folie à deux, are associated with aggression. The somatic subtype of DD is the one most often requiring palliative care at the end of life. Conclusions: We conclude that insufficient attention has been given to the care needs of the accelerated aging process in DD. Full article
14 pages, 497 KiB  
Review
Telephone-Delivered Interventions for Suicide Prevention in Schizophrenia and Related Disorders: A Systematic Review
by Laura Comendador, Ana Isabel Cebrià, Antoni Sanz, Víctor Pérez and Diego Palao
Healthcare 2023, 11(3), 432; https://doi.org/10.3390/healthcare11030432 - 02 Feb 2023
Viewed by 1581
Abstract
Background: Suicide is a health problem among patients diagnosed with schizophrenia. Telehealth technology has become an emerging intervention that may offer opportunities to reach this at-risk group. However, to consider the implementation of telehealth systems in the prevention of suicidal behaviors in patients [...] Read more.
Background: Suicide is a health problem among patients diagnosed with schizophrenia. Telehealth technology has become an emerging intervention that may offer opportunities to reach this at-risk group. However, to consider the implementation of telehealth systems in the prevention of suicidal behaviors in patients diagnosed with schizophrenia, a review of the evidence is required. The present aim was to explore the effectiveness of telephone-based suicide prevention programs among patients with schizophrenia and related disorders. Methods: A bibliographic search was carried out in the PubMed, PsycInfo, Scopus and Web of Science electronic databases following PRISMA guidelines. Two reviewers performed the selection, data extraction and methodological quality assessment. A total of 352 articles were retrieved, of which five studies met the eligibility criteria. Results: Globally, an adherence was observed ranging from 78 to 100%. Three studies reported a reduction in suicidal ideation and two studies showed a reduction in the risk of relapse observed in the intervention group compared to a control group. Conclusions: In accordance with the limited data available, the use of a telephone contact approach appears to be feasible and effective in schizophrenia patients with suicidal behaviors. The preliminary evidence also suggests that this system appears to reduce suicidal ideation. Further research is required to design evidence-based future interventions and to determine whether this approach can improve patient outcomes. Full article
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17 pages, 463 KiB  
Review
Collaboration between Psychiatrists and Other Allied Medical Specialists for the Treatment of Delusional Disorders
by Alexandre González-Rodríguez, José Antonio Monreal, Mentxu Natividad and Mary V. Seeman
Healthcare 2022, 10(9), 1729; https://doi.org/10.3390/healthcare10091729 - 08 Sep 2022
Cited by 2 | Viewed by 1845
Abstract
Background: There is increasing evidence that individuals with psychosis are at increased risk for cardiovascular disease, diabetes, metabolic syndrome, and several other medical comorbidities. In delusional disorder (DD), this is particularly so because of the relatively late onset age. Aims: The aim of [...] Read more.
Background: There is increasing evidence that individuals with psychosis are at increased risk for cardiovascular disease, diabetes, metabolic syndrome, and several other medical comorbidities. In delusional disorder (DD), this is particularly so because of the relatively late onset age. Aims: The aim of this narrative review is to synthesize the literature on the necessity for medical collaboration between psychiatrists and other specialists. Methods: A non-systematic narrative review was carried out of papers addressing referrals and cooperation among specialists in the care of DD patients. Results: Psychiatrists, the primary care providers for DD patients, depend on neurology to assess cognitive defects and rule out organic sources of delusions. Neurologists rely on psychiatry to help with patient adherence to treatment and the management of psychotropic drug side effects. Psychiatrists require ophthalmology/otolaryngology to treat sensory deficits that often precede delusions; reciprocally, psychiatric consults can help in instances of functional sensory impairment. Close collaboration with dermatologists is essential for treating delusional parasitosis and dysmorphophobia to ensure timely referrals to psychiatry. Conclusions: This review offers many other examples from the literature of the extent of overlap among medical specialties in the evaluation and effective treatment of DD. Optimal patient care requires close collaboration among specialties. Full article
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19 pages, 734 KiB  
Review
Dopamine, Psychosis, and Symptom Fluctuation: A Narrative Review
by Gabriela Novak and Mary V. Seeman
Healthcare 2022, 10(9), 1713; https://doi.org/10.3390/healthcare10091713 - 07 Sep 2022
Cited by 3 | Viewed by 2215
Abstract
It has been hypothesized since the 1960s that the etiology of schizophrenia is linked to dopamine. In the intervening 60 years, sophisticated brain imaging techniques, genetic/epigenetic advances, and new experimental animal models of schizophrenia have transformed schizophrenia research. The disease is now conceptualized [...] Read more.
It has been hypothesized since the 1960s that the etiology of schizophrenia is linked to dopamine. In the intervening 60 years, sophisticated brain imaging techniques, genetic/epigenetic advances, and new experimental animal models of schizophrenia have transformed schizophrenia research. The disease is now conceptualized as a heterogeneous neurodevelopmental disorder expressed phenotypically in four symptom domains: positive, negative, cognitive, and affective. The aim of this paper is threefold: (a) to review recent research into schizophrenia etiology, (b) to review papers that elicited subjective evidence from patients as to triggers and repressors of symptoms such as auditory hallucinations or paranoid thoughts, and (c) to address the potential role of dopamine in schizophrenia in general and, in particular, in the fluctuations in schizophrenia symptoms. The review also includes new discoveries in schizophrenia research, pointing to the involvement of both striatal neurons and glia, signaling pathway convergence, and the role of stress. It also addresses potential therapeutic implications. We conclude with the hope that this paper opens up novel avenues of research and new possibilities for treatment. Full article
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Other

6 pages, 229 KiB  
Viewpoint
Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis
by Riccardo Bortoletto and Marco Colizzi
Healthcare 2022, 10(8), 1553; https://doi.org/10.3390/healthcare10081553 - 16 Aug 2022
Cited by 4 | Viewed by 6461
Abstract
Being particularly vulnerable to the pro-psychotic effects of cannabinoid exposure, autism spectrum individuals present with an increased risk of psychosis, which may be passed on to their own children. More specifically, cannabis exposure among autism spectrum individuals seems to exert disruptive epigenetic effects [...] Read more.
Being particularly vulnerable to the pro-psychotic effects of cannabinoid exposure, autism spectrum individuals present with an increased risk of psychosis, which may be passed on to their own children. More specifically, cannabis exposure among autism spectrum individuals seems to exert disruptive epigenetic effects that can be intergenerationally inherited in brain areas which play a critical role in schizophrenia pathophysiology. Additionally, because of such cannabinoid-induced epigenetic effects, autism candidate genes present with bivalent chromatin markings which make them more vulnerable to subsequent disruption, possibly leading to psychosis onset later in life. Thus, findings support a developmental trajectory between autism and psychosis, as per endocannabinoid system modulation. However, such evidence has not received the attention it deserves. Full article
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