New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Antonio Ventriglio ◽  
Antonello Bellomo ◽  
Fabiana Ricci ◽  
Giuseppe Magnifico ◽  
Angelo Rinaldi ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Nmda Receptor Antagonist ◽  
Cochrane Library ◽  
First Episode ◽  
Positive Symptoms ◽  
Anti Psychotic ◽  
Residual Symptoms ◽  
Pharmacological Targets ◽  
The Cochrane Library

Background: The pharmacological treatment of schizophrenia is currently based on the employment of anti-psychotic medications showing an antagonism of dopaminergic and serotoninergic. 20-40% of patients are drug-resistant or residually symptomatic in the long-term anti-psychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. Methods: This systematic review summarized the evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, Google Scholar. Results: It has been extensively described the possible role of glutamate and its receptors as targets of the anti-psychotic mechanism of action. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. The rResults show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA:- Receptor antagonist) on cognition and psychopathology. It will be also discussed Tthe putative anti-psychotic effect of cannabidiol on positive symptoms and cognition will also be discussed, even if more evidence is required needing more evidences. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown improvements of in cognitive symptoms in schizophrenia as well as Erythropoietin. Oxytocin reported an antipsychotic-like effect and COX-2 inhibitors reported a reduction of positive symptoms of psychosis , above all in the first episode of illness. Conclusion: This narrative report suggests a promising role of new agents in the treatment of Schizophrenia, even if more research is needed to approve their clinical employment.

Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies

2021 ◽  
Vol 28 ◽  
Author(s):  
Adeleh Sahebnasagh ◽  
Fatemeh Saghafi ◽  
Sina Negintaji ◽  
Tingyan Hu ◽  
Mojtaba Shabani-Boroujeni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Cochrane Library ◽  
Signaling Molecule ◽  
No Donors ◽  
The Cochrane Library ◽  
Oxide Synthase

: In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low / moderate levels may favor tumorigenesis while higher levels would exert anti-tumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “double-edged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression, and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

New dopaminergic and non-dopaminergic theories in schizophrenia and their therapeutic impact

1997 ◽  
Vol 9 (2) ◽  
pp. 64-67
Author(s):  
R.S. Kahn
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Dopamine Neurons ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
The Core ◽  
Schizophrenic Patients ◽  
Core Symptoms ◽  
Influential Theory

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.

Epidemiology and pathobiology of bipolar disorder, and their exploration within a complete catchment area population

2000 ◽  
Vol 12 (3) ◽  
pp. 73-76 ◽  
Author(s):  
P.J. Scully ◽  
J.M. Owens ◽  
A. Kinsella ◽  
J.L. Waddington
Keyword(s):  
Bipolar Disorder ◽  
Life Events ◽  
Catchment Area ◽  
Negative Symptoms ◽  
Age At Onset ◽  
Later Life ◽  
Positive Symptoms ◽  
Left Hand ◽  
Duration Of Illness

ABSTRACTEpidemiological and pathobiological findings in bipolar disorder [BP] have often been limited by selection bias and lack of epidemiological representativeness. In a rural, circumscribed catchment area, ‘all’ patients with BP were identified and assessed. On preliminary analysis, morbid risk [MR] for BP over the area as a whole was 5.0 ± 0.6/1000. The distribution of MR for BP over geographical subregions showed no significant deviation from a statistical model for random occurrences in space by place at birth, in contrast to schizophrenia [SZ], and varied only modestly among males by place at onset. These results imply different etiological factors acting in BP in comparison with SZ, particularly with regard to the role of early versus later life events. In preliminary analyses of psychotic and cognitive features, current severity of positive symptoms was predicted in BP only by increasing dominance of the left hand; negative symptoms by duration of illness and current anticholinergic exposure; poorer general and frontal cognitive function by older age at onset of illness, increasing duration of illness, and current anticholinergic exposure. The finding on handedness suggests disturbance of cerebral asymmetry associated with positive symptoms in BP, while both negative symptoms and cognitive impairment may involve progressive processes. Further analysis of this epidemiologically complete population, including systematic comparisons of BP with schizoaffective disorder and SZ, continues.

Oral Flora and Perioperative Antimicrobial Interventions in Cleft Palate Surgery: A Review of the Literature

2020 ◽  
pp. 105566562097736
Author(s):  
Miles J. Pfaff ◽  
Leila Musavi ◽  
Maxwell M. Wang ◽  
Christos S. Haveles ◽  
Claire Liu ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Antibiotic Use ◽  
Fistula Formation ◽  
Cochrane Library ◽  
Oral Flora ◽  
Oronasal Fistula ◽  
Perioperative Antibiotics ◽  
Antimicrobial Interventions ◽  
The Cochrane Library

Background: The role of perioperative antibiotics in cleft palate remains a topic of debate. Advocates stress their importance in preventing local and systemic infections and decreasing the incidence of oronasal fistula formation. However, few studies to date have directly evaluated the role of antibiotics and other antimicrobial measures in cleft palate surgery. Objective: The aim of this review is to evaluate the evidence surrounding the use of perioperative antibiotics and other antimicrobial interventions in cleft palate surgery. Additionally, we review the literature on the oral flora unique to the cleft palate patient population. Methods: This was accomplished utilizing PubMed, Medline, and the Cochrane Library with MeSH and generic terms. Articles were selected based on predefined inclusion and exclusion criteria. Results: This review highlights the lack of higher level evidence on perioperative antibiotic use and other antimicrobial interventions in cleft palatoplasty and calls for further research on the matter. Conclusions: The literature appears to support the use of preoperative antibiotics for cleft palatoplasty, but the benefits of prolonged postoperative antibiotic use remain questionable.

Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning

2015 ◽  
Vol 45 (10) ◽  
pp. 2031-2043 ◽  
Author(s):  
J. Ventura ◽  
A. Ered ◽  
D. Gretchen-Doorly ◽  
K. L. Subotnik ◽  
W. P. Horan ◽  
...  
Keyword(s):  
Theory Of Mind ◽  
Negative Symptoms ◽  
Chronic Schizophrenia ◽  
First Episode ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Role Functioning ◽  
Recent Onset ◽  
Early Course ◽  
The Relationship

BackgroundNumerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning.MethodRecent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants’ descriptions of scenes depicting abstract visual stimuli ‘interacting’ in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed.ResultsOn the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms.ConclusionsThe ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.

scholarly journals Randomized Controlled Trial of Clozapine and CBT for First-Episode Psychosis with Enduring Positive Symptoms: A Pilot Study

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
J. Edwards ◽  
J. Cocks ◽  
P. Burnett ◽  
D. Maud ◽  
L. Wong ◽  
...  
Keyword(s):  
Pilot Study ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Treatment Phase ◽  
First Episode Psychosis ◽  
First Episode ◽  
Positive Symptoms ◽  
Treatment Groups ◽  
Episode Psychosis ◽  
Symptomatic Remission

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria () were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.

scholarly journals Aberrant effective connectivity is associated with positive symptoms in first-episode schizophrenia

2019 ◽  
Author(s):  
Martin J. Dietz ◽  
Yuan Zhou ◽  
Lotte Veddum ◽  
Christopher D. Frith ◽  
Vibeke F. Bliksted
Keyword(s):  
Social Cognition ◽  
Negative Symptoms ◽  
Effective Connectivity ◽  
Predictive Coding ◽  
First Episode ◽  
Positive Symptoms ◽  
Prediction Errors ◽  
Social Stimuli ◽  
Human Connectome Project ◽  
First Episode Schizophrenia

AbstractSchizophrenia is a tenacious psychiatric disorder thought to result from synaptic dysfunction. While symptomatology is traditionally divided into positive and negative symptoms, abnormal social cognition is now recognized a key component of schizophrenia. Nonetheless, we are still lacking a mechanistic understanding of how aberrant synaptic connectivity is expressed in schizophrenia during social perception and how it relates to positive and negative symptomatology. We used fMRI and dynamic causal modelling (DCM) to test for abnormalities in synaptic efficacy in twenty-four patients with first-episode schizophrenia (FES) compared to twenty-five matched controls performing the Human Connectome Project (HCP) social cognition paradigm. Patients had not received regular therapeutic antipsychotics, but were not completely drug naïve. Our data reveal an increase in excitatory feedforward connectivity from motion-sensitive V5 to posterior superior temporal sulcus (pSTS) in patients compared to matched controls. At the same time, were less accurate than controls in judging social stimuli from non-social stimuli. Crucially, patients with a higher degree of positive symptoms had more disinhibition within pSTS, a region computationally involved in Theory of Mind. We interpret these within a predictive coding framework where increased feedforward connectivity may encode aberrant prediction errors from V5 to hierarchically higher pSTS and local disinhibition within pSTS may reflect aberrant encoding of the precision of cortical representations about social stimuli.

scholarly journals Probiotics for the Prophylaxis of Migraine: A Systematic Review of Randomized Placebo Controlled Trials

2019 ◽  
Vol 8 (9) ◽  
pp. 1441 ◽  
Author(s):  
Malwina M. Naghibi ◽  
Richard Day ◽  
Samantha Stone ◽  
Ashton Harper
Keyword(s):  
Systematic Review ◽  
Outcome Measures ◽  
Gut Microbiome ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Qualitative Comparison ◽  
Microbiome Research ◽  
The Cochrane Library

Migraine is a common and disabling neurological condition with a complex etiology. Recent advances in the understanding of the gut microbiome have shown the role of gut micro-organisms in disease outcomes for distant organs—including the brain. Interventions targeting the gut microbiome have been shown to be effective in multiple neurological diagnoses, but there is little research into the role of the microbiome in migraine. This systematic review seeks to assess the current research landscape of randomized placebo controlled trials utilizing probiotic interventions as migraine prophylaxis. Searches were conducted of scientific databases including PubMed, MEDLINE, and the Cochrane Library, following PRISMA guidelines. Of 68 screened studies, 2 were eligible for analysis. Due to methodological differences, meta-analysis was not possible. Qualitative comparison of the studies demonstrated a dichotomy of results—one trial reported no significant change in migraine frequency and intensity, while the second trial reported highly significant improvements. No clear ‘gold standard’ currently exists for microbiome research, let alone for migraine-related microbiome research. The heterogeneity of outcome measures used in the two trials included in this systematic review shows the need for a standardization of outcome measures, therefore a series of recommendations for future probiotic–migraine research are included.

Toxic psychosis? Duration of untreated psychosis, symptomatology and cognitive deterioration in first episode psychosis

2007 ◽  
Vol 24 (4) ◽  
pp. 145-148 ◽  
Author(s):  
Richard Lawoyin ◽  
Keith Gaynor ◽  
Barbara Dooley ◽  
Elizabeth Lawlor ◽  
Mary Clarke ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
First Episode Psychosis ◽  
First Episode ◽  
Positive Symptoms ◽  
Cognitive Deterioration ◽  
Duration Of Untreated Psychosis ◽  
Episode Psychosis ◽  
The Relationship ◽  
Linear Regressions ◽  
Positive And Negative Symptoms

AbstractObjectives: To examine the relationship between cognitive deficits, the duration of untreated psychosis (DUP) and positive and negative symptoms in a first episode psychosis sample.Method: We assessed a consecutive sample of first episode psychosis participants from a catchment area service with a comprehensive neuropsychology battery, a family and service-user based measure of DUP and measures of symptomatology.Results: Using correlations and stepwise linear regressions, we found strong relationships between measures of DUP and positive symptomatology. We found that positive and negative symptoms were associated with different time periods within DUP. However, we did not find evidence of a relationship between DUP and cognitive factors.Conclusions: There was no evidence of a relationship between DUP and cognitive deterioration. However, there does appear to be evidence of a relationship between positive symptoms and aspects of DUP. These results highlight the importance of the heterogeneity of DUP and the potential to reduce positive symptoms through early intervention.

Treatment of the patient with long-term schizophrenia

1997 ◽  
Vol 3 (6) ◽  
pp. 339-346 ◽  
Author(s):  
Ann Mortimer
Keyword(s):  
Negative Symptoms ◽  
Chronic Illnesses ◽  
First Episode ◽  
Positive Symptoms ◽  
Loss Of Self ◽  
Appropriate Treatment ◽  
Community Skills ◽  
First Episode Of Schizophrenia ◽  
Over Time

At most, 15% of patients in Western countries remain free of relapse after their first episode of schizophrenia (Crow et al, 1986). Like many chronic illnesses, schizophrenia can be controlled by appropriate treatment, but there may be a gradual deterioration over time. This encompasses problems such as loss of self-care, communication and community skills; negative symptoms of poverty of affect and ideation; cognitive impairment; behaviour problems such as aggression; and poorly controlled positive symptoms.

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