Where Are We in Understanding Schizophrenia? From Bench to Bedside and Back

A special issue of Behavioral Sciences (ISSN 2076-328X). This special issue belongs to the section "Experimental and Clinical Neurosciences".

Deadline for manuscript submissions: closed (28 November 2021) | Viewed by 19733

Special Issue Editors


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Guest Editor
Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA
Interests: schizophrenia research; psychoneuroimmunology; psychopharmacology

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Guest Editor
University of Texas Health Science Center at Houston, Houston, USA

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Guest Editor
Touro University Nevada, Nevada, USA

Special Issue Information

Dear Colleagues,

In 1899, Emil Kraepelin first described schizophrenia as dementia praecox, primarily due to an early onset and a long course of cognitive decline. Over a century later, we are yet to discover the exact cause of schizophrenia, which explains the failure to develop curative treatments for this complex psychiatric disorder.  We have also not been able to develop valid and reliable biomarkers for schizophrenia diagnosis, which is still based on history and mental status examination, the same method employed by Kraepelin over a century ago. Moreover, a significant percentage of individuals with schizophrenia still have a deteriorating clinical course and die 15-20 years earlier than the general population. To elucidate the pathophysiological mechanisms underlying schizophrenia, develop more effective treatments with minimal side effects, and create services tailored towards the unique needs of patients, the field must incorporate data derived from studies using diverse research methods. We have therefore launched this special issue as a forum to publish studies from researchers employing a wide range of research methods and technologies to study schizophrenia. We welcome original paper, review, or meta-analysis based on animal and human studies. We will consider papers reporting observational, clinical trial, genetics, imaging, computational, health services research, ecological and in vitro data. All submitted manuscripts will be reviewed by at least two reviewers and if accepted will be subject to the article processing charges.

Dr. Olaoluwa Okusaga
Dr. Consuelo Walss-Bass
Dr. Mujeeb Shad
Guest Editors

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Keywords

  • Schizophrenia
  • basic science
  • clinical science
  • in vitro studies, population studies, ecological studies

Published Papers (5 papers)

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Review

11 pages, 460 KiB  
Review
The Association of the Gut Microbiota with Clinical Features in Schizophrenia
by Annamarie Nocera and Henry A. Nasrallah
Behav. Sci. 2022, 12(4), 89; https://0-doi-org.brum.beds.ac.uk/10.3390/bs12040089 - 25 Mar 2022
Cited by 6 | Viewed by 6221
Abstract
The connection between gut microbiota and schizophrenia has become a fertile area of research. The relationship is bidirectional and quite complex, but is likely to lead to practical clinical applications. For example, commensal microbiota have been shown to produce inflammatory metabolites that can [...] Read more.
The connection between gut microbiota and schizophrenia has become a fertile area of research. The relationship is bidirectional and quite complex, but is likely to lead to practical clinical applications. For example, commensal microbiota have been shown to produce inflammatory metabolites that can cross the blood–brain barrier—a possible neurobiological precursor of psychosis. Antipsychotics that treat these individuals have been shown to alter gut microbiota. On the other hand, life style in schizophrenia, such as diet and decreased exercise, can be disruptive to the normal microbiome diversity. In the present paper, we conduct a review of PubMed literature focusing on the relationship of gut microbiota with clinical symptoms of schizophrenia, which, to our knowledge, has not yet been reviewed. Numerous clinical characteristics were identified correlating to gut microbial changes, such as violence, negative symptoms, treatment resistance, and global functioning. The most consistently demonstrated correlations to gut microbial changes across studies were for the overall symptom severity and negative symptom severity. Although numerous studies found changes in these domains, there is much variability between the bacteria that change in abundance between studies, likely due to the regional and methodological differences between studies. The current literature shows promising correlations between gut microbiota profiles and several clinical features of schizophrenia, but initial studies require replication. Full article
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13 pages, 282 KiB  
Review
The Limits between Schizophrenia and Bipolar Disorder: What Do Magnetic Resonance Findings Tell Us?
by Mirona Letitia Dobri, Alexandre Paim Diaz, Sudhakar Selvaraj, Joao Quevedo, Consuelo Walss-Bass, Jair C. Soares and Marsal Sanches
Behav. Sci. 2022, 12(3), 78; https://0-doi-org.brum.beds.ac.uk/10.3390/bs12030078 - 15 Mar 2022
Cited by 3 | Viewed by 2692
Abstract
Schizophrenia and bipolar disorder, two of the most severe psychiatric illnesses, have historically been regarded as dichotomous entities but share many features of the premorbid course, clinical profile, genetic factors and treatment approaches. Studies focusing on neuroimaging findings have received considerable attention, as [...] Read more.
Schizophrenia and bipolar disorder, two of the most severe psychiatric illnesses, have historically been regarded as dichotomous entities but share many features of the premorbid course, clinical profile, genetic factors and treatment approaches. Studies focusing on neuroimaging findings have received considerable attention, as they plead for an improved understanding of the brain regions involved in the pathophysiology of schizophrenia and bipolar disorder. In this review, we summarize the main magnetic resonance imaging findings in both disorders, aiming at exploring the neuroanatomical and functional similarities and differences between the two. The findings show that gray and white matter structural changes and functional dysconnectivity predominate in the frontal and limbic areas and the frontotemporal circuitry of the brain areas involved in the integration of executive, cognitive and affective functions, commonly affected in both disorders. Available evidence points to a considerable overlap in the affected regions between the two conditions, therefore possibly placing them at opposite ends of a psychosis continuum. Full article
15 pages, 806 KiB  
Review
Dopamine, Serotonin, and Structure/Function Brain Defects as Biological Bases for Treatment Response in Delusional Disorder: A Systematic Review of Cases and Cohort Studies
by Armand Guàrdia, Alexandre González-Rodríguez, Mary V. Seeman, Aida Álvarez, Francesc Estrada, Sidharta Acebillo, Javier Labad and José A. Monreal
Behav. Sci. 2021, 11(10), 141; https://0-doi-org.brum.beds.ac.uk/10.3390/bs11100141 - 19 Oct 2021
Cited by 5 | Viewed by 3302
Abstract
Although blockade of dopamine receptors D2 and D3 appears to be the main mechanism of antipsychotic action, treatment response variability calls for an examination of other biological systems. Our aim is to systematically review reports of treatment response in delusional disorder (DD) in [...] Read more.
Although blockade of dopamine receptors D2 and D3 appears to be the main mechanism of antipsychotic action, treatment response variability calls for an examination of other biological systems. Our aim is to systematically review reports of treatment response in delusional disorder (DD) in order to help determine its biological bases. Computerized searches of ClinicalTrials.gov, PubMed, and Scopus databases (from 1999 to September 2021) were systematically reviewed, in keeping with PRISMA directives. We used the search terms: (treat * OR therap * AND (delusional disorder)). We included all studies that explored the biological mechanisms of treatment response in DD, as diagnosed by ICD or DSM criteria. A total of 4344 records were initially retrieved, from which 14 papers were included: case reports, case series, and cohort studies. Findings point to (1) dopaminergic dysfunction (based on biochemical and genetic studies), (2) serotonergic dysfunction (based on partial agonism/antagonism of drugs), and (3) brain structure/function impairment, especially in the temporal and parietal lobes, as crucial factors in treatment response. Further studies with higher levels of evidence are needed to help clinicians determine treatment. Full article
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22 pages, 443 KiB  
Review
Genetic Testing for Antipsychotic Pharmacotherapy: Bench to Bedside
by Mujeeb U. Shad
Behav. Sci. 2021, 11(7), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/bs11070097 - 30 Jun 2021
Cited by 4 | Viewed by 2986
Abstract
There is growing research interest in learning the genetic basis of response and adverse effects with psychotropic medications, including antipsychotic drugs. However, the clinical utility of information from genetic studies is compromised by their controversial results, primarily due to relatively small effect and [...] Read more.
There is growing research interest in learning the genetic basis of response and adverse effects with psychotropic medications, including antipsychotic drugs. However, the clinical utility of information from genetic studies is compromised by their controversial results, primarily due to relatively small effect and sample sizes. Clinical, demographic, and environmental differences in patient cohorts further explain the lack of consistent results from these genetic studies. Furthermore, the availability of psychopharmacological expertise in interpreting clinically meaningful results from genetic assays has been a challenge, one that often results in suboptimal use of genetic testing in clinical practice. These limitations explain the difficulties in the translation of psychopharmacological research in pharmacogenetics and pharmacogenomics from bench to bedside to manage increasingly treatment-refractory psychiatric disorders, especially schizophrenia. Although these shortcomings question the utility of genetic testing in the general population, the commercially available genetic assays are being increasingly utilized to optimize the effectiveness of psychotropic medications in the treatment-refractory patient population, including schizophrenia. In this context, patients with treatment-refractory schizophrenia are among of the most vulnerable patients to be exposed to the debilitating adverse effects from often irrational and high-dose antipsychotic polypharmacy without clinically meaningful benefits. The primary objective of this comprehensive review is to analyze and interpret replicated findings from the genetic studies to identify specific genetic biomarkers that could be utilized to enhance antipsychotic efficacy and tolerability in the treatment-refractory schizophrenia population. Full article
15 pages, 1139 KiB  
Review
Repetitive Transcranial Magnetic Stimulation: A Potential Treatment for Obesity in Patients with Schizophrenia
by Ramey G. Monem and Olaoluwa O. Okusaga
Behav. Sci. 2021, 11(6), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/bs11060086 - 11 Jun 2021
Cited by 4 | Viewed by 3621
Abstract
Obesity is highly prevalent in patients with schizophrenia and, in association with metabolic syndrome, contributes to premature deaths of patients due to cardiovascular disease complications. Moreover, pharmacologic, and behavioral interventions have not stemmed the tide of obesity in schizophrenia. Therefore, novel effective interventions [...] Read more.
Obesity is highly prevalent in patients with schizophrenia and, in association with metabolic syndrome, contributes to premature deaths of patients due to cardiovascular disease complications. Moreover, pharmacologic, and behavioral interventions have not stemmed the tide of obesity in schizophrenia. Therefore, novel effective interventions are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for inducing weight loss in obese non-psychiatric samples but this promising intervention has not been evaluated as a weight loss intervention in patients with schizophrenia. In this narrative review, we describe three brain mechanisms (hypothalamic inflammation, dysregulated mesocorticolimbic reward system, and impaired prefrontal cortex function) implicated in the pathogenesis and pathophysiology of obesity and emphasize how the three mechanisms have also been implicated in the neurobiology of schizophrenia. We then argue that, based on the three overlapping brain mechanisms in obesity and schizophrenia, rTMS would be effective as a weight loss intervention in patients with schizophrenia and comorbid obesity. We end this review by describing how deep TMS, relative to conventional TMS, could potentially result in larger effect size for weight loss. While this review is mainly conceptual and based on an extrapolation of findings from non-schizophrenia samples, our aim is to stimulate research in the use of rTMS for weight loss in patients with schizophrenia. Full article
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