scholarly journals Neuroprotective effect of hesperidin and its combination with coenzyme Q10 on an animal model of ketamine-induced psychosis: behavioral changes, mitochondrial dysfunctions, and oxidative stress

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Naresh Kumar ◽  
Monu Yadav ◽  
Anil Kumar ◽  
Monika Kadian ◽  
Sunil Kumar
Keyword(s):  
Locomotor Activity ◽  
Side Effects ◽  
Coenzyme Q10 ◽  
Negative Symptoms ◽  
Behavioral Changes ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Immobility Duration ◽  
Olanzapine Treatment ◽  
Mitochondrial Functions

Abstract Background Psychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline. Clinically available medicines are associated with some serious side effects which limit their use. Treatment with flavonoids has been associated with delayed onset and development, decreased risk, or increased improvement of various neuropsychiatric disorders including psychosis with negligible side effects. Therefore, the present study was aimed to investigate the protective effects of hesperidin (flavonoid) alone or its combination with coenzyme Q10 against ketamine-induced psychotic symptoms in mice. Results Ketamine (50 mg/kg, i.p.) was given for 21 days to induce psychosis in Laca mice of either sex. Locomotor activity and stereotypic behaviors, immobility duration (forced swim test), and increased transfer latency (elevated plus maze) were performed to test the effect of hesperidin (50 mg/kg, 100 mg/kg, 200 mg/kg, p.o.) and coenzyme Q10 (20 mg/kg, 40 mg/kg, p.o.) and combination of hesperidin + coenzyme Q10 followed by biochemical and mitochondrial complexes assays. For 21 days, ketamine (50 mg/kg, i.p.) administration significantly produced increased locomotor activity and stereotypic behaviors (positive symptoms), increased immobility duration (negative symptoms) and cognitive deficits (increases transfer latency) weakens oxidative defense and mitochondrial function. Further, 21 days’ administration of hesperidin and coenzyme Q10 significantly reversed the ketamine-induced psychotic behavioral changes and biochemical alterations and mitochondrial dysfunction in the discrete areas (prefrontal cortex and hippocampus) of mice brains. The potential effect of these drugs was comparable to olanzapine treatment. Moreover, the combination of hesperidin with coenzyme Q10 and or a combination of hesperidin + coenzyme Q10 + olanzapine treatment did not produce a significant effect compared to their per se effect in ketamine-treated animals. Conclusions The study revealed that hesperidin alone or in combination with coenzyme Q10 could reduce psychotic symptoms and improve mitochondrial functions and antioxidant systems in mice, suggesting neuroprotective effects against psychosis.

Evaluation of positive and negative symptoms in schizophrenia

1986 ◽  
Vol 1 (2) ◽  
pp. 108-122 ◽  
Author(s):  
Nancy C. Andreasen ◽  
William M. Grove
Keyword(s):  
Negative Symptoms ◽  
The United States ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
University Of Iowa ◽  
Normal Functions ◽  
Subsequent Investigation ◽  
The University ◽  
The Relationship ◽  
Positive And Negative Symptoms

SummaryMost investigators concur that schizophrenia is probably a heterogeneous group of disorders that share the common features of psychotic symptoms, partial response to neuroleptics, and a relatively poor outcome. The subdivision of schizophrenia into two subtypes, positive versus negative, has achieved wide acceptance throughout the world during recent years. This distinction has heuristic and theoretical appeal because it unites phenomenology, pathophysiology, and etiology into a single comprehensive hypothesis.In spite of its wide appeal, the distinction has a number of problems. These include the failure to distinguish between symptom syndromes and diseases; failure to deal with the mixed patient; failure to take longitudinal course into account; and failure to address conceptually and methodologically the distinction between positive and negative symptoms.This paper focuses primarily on the conceptual basis for two instruments designed to measure positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), originally described in 1982. Since their description, these scales have been used in a variety of other centers. These scales are based on the hypothesis that negative symptoms represent a deficit or diminution in normal psychological functions wliile positive symptoms represent an excess or distortion of normal functions. Reliability data are now available from Italy, Spain, and Japan which suggest that these scales can be used reliably in cultural settings outside the United States. The results of these studies are summarized in this paper. In addition, a replication study involving a new sample of 117 schizophrenics collected at the University of Iowa is described. In this second study of the SANS and SAPS, internal consistency is found to be quite high in the SANS. Thus negative symptoms appear to be more internally correlated with one another than are positive symptoms. The implications of this result are discussed. A principal components analysis is used to explore the relationship between positive and negative symptoms. While the study reported in 1982 suggested that positive and negative symptoms are negatively correlated, in the present study they appear to be uncorrelated. Overall, the results suggest that the SANS and SAPS are useful comprehensive instruments for the evaluation of positive and negative symptoms. The relationship between these symptoms and external validators such as cognitive functioning or CT scan abnormalities will be reported in a subsequent investigation.

ARE SOME TYPES OF PSYCHOTIC SYMPTOMS MORE RESPONSIVE TO COGNITIVE-BEHAVIOUR THERAPY?

2001 ◽  
Vol 29 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Nicholas Tarrier ◽  
Caroline Kinney ◽  
Ellis McCarthy ◽  
Anja Wittkowski ◽  
Lawrence Yusupoff ◽  
...  
Keyword(s):  
Cognitive Behaviour Therapy ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Chronic Schizophrenia ◽  
Routine Care ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Behaviour Therapy ◽  
Cognitive Behaviour ◽  
Supportive Counselling

Results are presented from a randomized controlled trial indicating which psychotic symptoms respond to cognitive behaviour therapy. The aim of the study was to investigate whether different types of psychotic symptoms are more or less responsive to cognitive-behaviour therapy compared to treatment received by control groups. Seventy-two patients suffering from chronic schizophrenia who experienced persistent positive psychotic symptoms were assessed at baseline and randomized to either cognitive-behaviour therapy and routine care, supportive counselling and routine care, or routine care alone and were re-assessed after 3 months of treatment (post-treatment). Independent and blind assessment of outcome indicated delusions significantly improved with both cognitive behaviour therapy and supportive counselling compared to routine care. Hallucinations significantly decreased with cognitive-behaviour therapy compared to supportive counselling. There was no difference in the percentage change of hallucinations compared to delusions in patients treated by cognitive behaviour therapy. There was little change in measures of affective symptoms but there was no evidence that a reduction in positive symptoms was associated with an increase in depres sion. In fact, a reduction in positive symptoms was positively correlated with a reduction in depression. There were significant differences in the reductions in thought disorder and negative symptoms with an advantage of cognitive-behaviour therapy compared to routine care.

The core dimensions of schizophrenia

2020 ◽  
pp. 565-573
Author(s):  
Nancy C Andreasen
Keyword(s):  
Intelligence Quotient ◽  
Negative Symptoms ◽  
Three Dimensions ◽  
Psychotic Symptoms ◽  
Outcome Predictors ◽  
Positive Symptoms ◽  
Illness Onset ◽  
Premorbid Adjustment ◽  
High Intelligence ◽  
Over Time

Schizophrenia is a devastating illness that usually affects many aspects of a person’s life. The symptoms may be divided into two groups. ‘Positive’ symptoms include a variety of psychotic symptoms such as delusions and hallucinations. Although severe, they are less handicapping than negative symptoms such as avolition or anhedonia. Positive symptoms involve the presence of things that should be absent, while negative symptoms involve the absence of things that should be present. Dimensional approaches for classifying symptoms have also become popular in current nosology, proposing three dimensions: positive, negative, and disorganized. The course of the illness evolves over time; a prodrome is often present, followed by illness onset and a variable outcome. Good outcome predictors include good premorbid adjustment, high intelligence quotient, and good social relationships. The pathophysiology of the illness includes genetic, neuropathological, and neurodevelopmental components. A possible association with creativity may suggest reasons why the illness has persisted over many centuries.

scholarly journals M216. ASSOCIATIONS OF EXTRAPYRAMIDAL SYMPTOMS WITH PSYCHOTIC SYMPTOMS IN A COHORT OF HOMELESS OR PRECARIOUSLY HOUSED PERSONS WITH OR WITHOUT SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S218-S218
Author(s):  
David Kim ◽  
Ric Procyshyn ◽  
Lik Hang Lee ◽  
William Panenka ◽  
Olga Leonova ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Extrapyramidal Symptoms ◽  
Analysis Of Covariance ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Syndrome Scale ◽  
Clinically Significant

Abstract Background There is considerable evidence supporting the association between extrapyramidal symptoms (EPS) and psychotic symptoms in patients with schizophrenia (SCZ). However, it is not well understood whether such an association exists in individuals without SCZ and how the association differs from those with SCZ. Our aim was to examine the associations of EPS with psychotic symptoms and compare them between SCZ and non-SCZ individuals. Methods We used data from a 10-year community-based study of homeless or precariously housed persons from Vancouver, Canada. Diagnosis of SCZ was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Severity of psychotic symptoms was rated using the Positive and Negative Syndrome Scale (PANSS). Severity of parkinsonism, dyskinesia, and dystonia was rated using the Extrapyramidal Symptom Rating Scale (ESRS), and akathisia using the Barnes Akathisia Rating Scale (BARS). Presence of EPS was defined as having at least moderate severity on the ESRS (i.e., ≥4 out of 8) or BARS (i.e., ≥3 out of 5) Clinical Global Impression-Severity (CGI-S) scale. Absence of EPS was defined as scoring ≤2 on the ESRS or ≤1 on the BARS CGI-S scale. Two-way analysis of covariance was performed using SCZ and EPS as independent variables and PANSS five factors (i.e., positive symptoms, negative symptoms, disorganization, excitement, and depression) as dependent variables, controlling for age, antipsychotic users, and cocaine- or methamphetamine-dependent individuals. Multiple linear regression analysis was performed for both SCZ and non-SCZ groups, controlling for the same confounding variables, to examine 1) associations of the severity of EPS subtypes with PANSS factors and 2) whether the presence of multiple EPS subtypes would be associated with increased SCZ symptoms relative to the presence of a single subtype. Results A total of 223 participants were included in this study (mean age: 44.1 ± 12.0 years; 76.1% male). Eighty-four participants met the diagnosis of SCZ, of whom 39 met our criteria for having EPS and 32 for not having EPS. The remaining 139 participants were not diagnosed with SCZ, of whom 50 had EPS and 72 did not. None of the participants had clinically significant dystonia. Overall, significant main effects of EPS were found for total symptoms (F1,182 = 24.4, p < 0.001), negative symptoms (F1,182 = 16.3, p < 0.001), disorganization (F1,181 = 16.6, p < 0.001), and excitement (F1,182 = 15.8, p < 0.001), but not positive symptoms or depression. The presence of EPS was associated with greater total symptoms and disorganization in both SCZ and non-SCZ groups. Significant interaction effects between SCZ and EPS were found for negative symptoms (F1,182 = 6.0, p = 0.015) and excitement (F1,182 = 3.9, p = 0.050), where the presence of EPS was associated with greater negative symptoms and excitement in SCZ participants, but not in non-SCZ participants. Consistent in both SCZ and non-SCZ groups, there were significant positive associations of the severity of 1) parkinsonism with negative symptoms, 2) dyskinesia with disorganization and total symptoms, and 3) akathisia with excitement. The presence of multiple EPS subtypes, relative to a single subtype, was not associated with significant increases in any SCZ symptoms, except a significant increase in excitement in non-SCZ participants. Discussion The presence of EPS is clearly associated with greater symptoms of SCZ, even in individuals without SCZ. People with SCZ may experience greater negative symptoms and excitement as a result of EPS than those without SCZ. Subtypes of EPS are distinctively associated with factors of SCZ symptoms. Future studies should elucidate the mechanisms underlying these associations.

scholarly journals Meta-analysis and Meta-regression of Cognitive Behavioral Therapy for Psychosis (CBTp) Across Time: The Effectiveness of CBTp has Improved for Delusions

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Katarzyna Sitko ◽  
Bridgette M Bewick ◽  
David Owens ◽  
Ciara Masterson
Keyword(s):  
Cognitive Behavioral Therapy ◽  
Negative Symptoms ◽  
Behavioral Therapy ◽  
Meta Analysis ◽  
Cognitive Behavioral ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Medium Effects ◽  
Treatment As Usual ◽  
Meta Analyses

Abstract Published research shows small-to-medium effects of Cognitive Behavioral Therapy for Psychosis (CBTp) on reducing psychotic symptoms. Given the on-going development of CBTp interventions, the aim of this systematic review is to examine whether the effectiveness of CBTp has changed across time. MEDLINE, EMBASE, PsycINFO, and CENTRAL were searched for randomized controlled trials examining CBTp interventions targeting positive and/or negative symptoms vs treatment as usual. Four meta-analyses were carried out to examine the effectiveness of CBTp for: positive symptoms; delusions; hallucinations; and negative symptoms. Four meta-regressions examined whether the effectiveness of CBTp changed across time for these groups of symptoms. A total of 28 studies (n = 2698) yielded a pooled g of −0.24 (95% confidence interval [CI] −0.32, −0.16, P < .001) favoring CBTp for positive symptoms, with nonsignificant heterogeneity (Q = 26.87, P = .47; I2 =0%); 13 studies (n = 890) yielded a pooled g of −0.36 (95% CI −0.59, −0.13, P = .002) for delusions, with substantial heterogeneity (Q = 31.99, P = .001; I2 =62%); 16 studies (n = 849) yielded a pooled g of −0.26 (95% CI −0.42, −0.11, P < .001) for hallucinations, with nonsignificant heterogeneity (Q = 18.10, P = .26; I2 =17%); 19 studies (n = 1761) yielded a pooled g of −0.22 (95% CI −0.33, −0.12, P < .001) for negative symptoms, with nonsignificant heterogeneity (Q = 20.32, P = .32, I2 =11%). Meta-regressions indicated a significant effect of year on the effectiveness of CBTp only for delusions (F[1, 11] = 5.99, P = .032; R2 = 0.594); methodological quality did not effect this finding. Findings indicate small-to-medium effects of CBTp for psychotic symptoms, with increasing effectiveness across time for delusions.

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.

Relationship Between Childhood Trauma and Psychotic Symptoms in Patients with Schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S269-S269
Author(s):  
E.E. Kılıçaslan ◽  
A. Esen ◽  
M. Izci Kasal ◽  
E. Ozelci ◽  
B. Murat ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Childhood Trauma ◽  
Stepwise Regression ◽  
Negative Symptoms ◽  
Depressive Symptomatology ◽  
Short Form ◽  
Depression Scale ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Childhood Trauma Questionnaire

IntroductionThe association between childhood trauma and psychotic symptoms is still not clearly understood. Findings for positive and negative symptoms are confounding. This symptomatic response may differ according to the type of childhood trauma, for example childhood abuse was associated with positive symptoms while childhood neglect was associated with negative symptoms.ObjectivesThis study examined the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality.MethodsThe childhood trauma questionnaire – short form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia, Pittsburgh sleep quality index, and the suicidality subscale of mini-international neuropsychiatric interview were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology and total symptoms of schizophrenia were dependent variables.ResultsDepressive symptomatology and childhood physical abuse (CPA) significantly contributed to positive, negative, general psychopathology and global schizophrenia symptomatology. Stepwise regression analysis results are presented in Table 1.ConclusionsOur findings suggest that CPA during childhood could have an impact on psychopathology in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Current use of atypical antipsychotics

2002 ◽  
Vol 17 (S4) ◽  
pp. 377s-384s ◽  
Author(s):  
F. Müller-Spahn
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Term Treatment ◽  
Dopamine Neurons ◽  
Positive Symptoms ◽  
Onset Of Action ◽  
Conventional Antipsychotics ◽  
Long Term Treatment ◽  
Insufficient Response

SummaryIn terms of the phenomenology of schizophrenia, there are four targets for drug treatments: positive symptoms, negative symptoms, affective dysfunction, and cognitive dysfunction. Because of the side-effects of both conventional antipsychotics and the new atypicals, there still is a need to search for better-tolerated antipsychotics. Conventional antipsychotics have two principal limitations: 30–40% of patients have an insufficient response to them, and they have a large variety of adverse effects. Side-effects will reduce patients’ compliance with treatment, as well as their immediate quality of life, and may therefore unfavorably affect rehabilitation. Four principal features differentiate atypical from conventional antipsychotics, yet have not been established for all atypicals: fewer extrapyramidal side-effects, greater efficacy in the treatment of negative symptoms, specific pharmacological receptor binding profiles, and greater selective effect on the mesolimbic dopamine neurons than on nigrostriatal neurons. The pharmacological profile of amisulpride is completely different to that of other atypical antipsychotics. It has a high selectivity for D2 and D3 dopamine receptors, and thus would be expected to be devoid of unwanted side-effects associated with action on other neurotransmitter systems. It acts preferentially on the mesocortical and mesolimbic systems. It has an earlier onset of action than haloperidol. Amisulpride is a compound with a dual mode of action. At low doses it blocks presynaptic dopamine autoreceptors, inducing an increased dopaminergic neurotransmission, and at high doses it blocks postsynaptic dopaminergic activity. It is at least as effective as haloperidol, flupenthixol, and risperidone in controlling positive symptoms, as well as having efficacy for negative symptoms. It has less propensity to induce weight gain than do other atypical antipsychotics. For the 60–80% of patients with schizophrenia who require long-term treatment, drug tolerability is crucially important, as it will improve compliance, and therefore reduce relapse rate.

The time course of psychotic symptom side effects of ketamine in the treatment of depressive disorders: a systematic review and meta-analysis

2020 ◽  
pp. 103985622096164
Author(s):  
Maryam Tashakkori ◽  
Andrew Ford ◽  
Milan Dragovic ◽  
Laura Gabriel ◽  
Flavie Waters
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Psychotic Symptom ◽  
Repeated Measures ◽  
Time Course ◽  
Meta Analysis ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Symptom Change ◽  
Repeated Measures Design

Objective: Ketamine is a potential rapid-acting treatment for depression. Studies have suggested that the side effects are minimal and temporary, but the psychotic symptom side effects have yet to be fully examined. This study investigated whether ketamine infusion in the treatment of mood disorders is associated with increases in positive symptoms and whether these symptom effects endure over time. Methods: A systematic review and meta-analysis of studies of ketamine in the treatment of depression. Embase and Medline databases were searched for studies including (a) participants with major affective disorders, (b) 0.4 or 0.5 mg intravenously administered ketamine, (c) measurement of positive symptoms using BPRS+, and (d) a within-subject repeated-measures design with participants serving as their own baseline. Results: Seventeen studies met the inclusion criteria, comprising 458 participants. The meta-analyses examined symptom change occurring within the first 4 h, after 1 day, and after 3 days. Results showed significant BPRS+ increases within the first 30–60 min in 72% of studies, followed by a return to baseline levels. Conclusion: Peak symptom change occurred within the first hour post infusion. There are limited data to determine if ketamine is safe in the longer term, but there were no indications that psychotic symptoms re-occurred after the first hour and in the days following administration.

Persistent Psychotic Symptoms at Discharge in Patients with Schizophrenia

1988 ◽  
Vol 22 (2) ◽  
pp. 166-172 ◽  
Author(s):  
I. H. Minas ◽  
S. D. Joshua ◽  
H. J. Jackson ◽  
P. M. Burgess
Keyword(s):  
Negative Symptoms ◽  
Community Care ◽  
Early Discharge ◽  
Community Services ◽  
Government Policies ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Positive And Negative Symptoms

A sample of patients with DSM-III schizophrenia was examined and rated using Andreasen's Schedule for the Assessment of Positive Symptoms (SAPS) and the Schedule for the Assessment of Negative Symptoms (SANS), soon after admission and in the week prior to discharge. A high proportion of the sample had persistent positive and negative symptoms at discharge. This finding is discussed in relation to the service demands placed on the hospital, changing government policies concerning hospital and community care, and the possible consequences of early discharge policies in the absence of adequate community services.

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