scholarly journals Cannabidiol modulation of hippocampal glutamate in early psychosis

2021 ◽  
pp. 026988112110011
Author(s):  
Aisling O’Neill ◽  
Luciano Annibale ◽  
Grace Blest-Hopley ◽  
Robin Wilson ◽  
Vincent Giampietro ◽  
...  
Keyword(s):  
Scale Score ◽  
Drug Administration ◽  
Symptom Severity ◽  
Repeated Measures ◽  
Negative Relationship ◽  
Resonance Spectroscopy ◽  
Neurochemical Mechanisms ◽  
Antipsychotic Effect ◽  
Syndrome Scale ◽  
Negative Syndrome

Background: Emerging evidence supports the antipsychotic effect of cannabidiol, a non-intoxicating component of cannabis, in people with psychosis. Preclinical findings suggest that this antipsychotic effect may be related to cannabidiol modulating glutamatergic signalling in the brain. Aim: The purpose of this study was to investigate the effects of cannabidiol on the neurochemical mechanisms underlying psychosis. Methods: We investigated the effects of a single oral dose of cannabidiol (600 mg) in patients with psychosis, using a double-blind, randomised, placebo-controlled, repeated-measures, within-subject cross-over design. After drug administration, 13 patients were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was rated using the Positive and Negative Syndrome Scale 60 min before drug administration (pre-scan), and 270 min after drug administration (post-scan). Effects of cannabidiol on hippocampal glutamate levels, symptom severity, and correlations between hippocampal glutamate and symptoms were investigated. Results: Compared to placebo, there was a significant increase in hippocampal glutamate ( p=0.035), and a significantly greater decrease in symptom severity ( p=0.032) in the psychosis patients under cannabidiol treatment. There was also a significant negative relationship between post-treatment total Positive and Negative Syndrome Scale score and hippocampal glutamate ( p=0.047), when baseline Positive and Negative Syndrome Scale score, treatment (cannabidiol vs placebo), and interaction between treatment and glutamate levels were controlled for. Conclusions: These findings may suggest a link between the increase in glutamate levels and concomitant decrease in symptom severity under cannabidiol treatment observed in psychosis patients. Furthermore, the findings provide novel insight into the potential neurochemical mechanisms underlying the antipsychotic effects of cannabidiol.

scholarly journals O5.2. CBD MODULATION OF HIPPOCAMPAL GLUTAMATE IN PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Aisling O’Neill ◽  
Luciano Annibale ◽  
Grace Blest-Hopley ◽  
Robin Wilson ◽  
Sagnik Bhattacharyya
Keyword(s):  
Drug Administration ◽  
Repeated Measures ◽  
Placebo Treatment ◽  
Psychotic Symptoms ◽  
Resonance Spectroscopy ◽  
Treatment Change ◽  
Double Blind ◽  
Antipsychotic Effect ◽  
Syndrome Scale ◽  
Dopaminergic Neurotransmitter

Abstract Background Emerging evidence supports the antipsychotic effect of cannabidiol (CBD), a non-intoxicating component of cannabis, in people with psychosis. However, how CBD might exert its antipsychotic effect remains unclear. While current antipsychotic medications typically target the dopaminergic neurotransmitter system, preclinical findings suggest that CBD may directly or indirectly affect multiple distinct modes of neural signalling, including both glutamate and dopamine. However, no study has as yet investigated the effect of CBD on brain glutamate levels in patients with psychosis as a potential mechanism underlying its antipsychotic effects. Methods We investigated the effects of a single oral dose of CBD (600mg), compared to a matched placebo, in patients within 5 years of onset of psychosis, using a double-blind, randomized, placebo-controlled, repeated-measures, within-subject cross-over design, with at least a one-week interval between scans to allow washout of CBD. After drug administration, 13 patients (mean age 27.73, 66.7% male) were scanned using proton magnetic resonance spectroscopy to measure left hippocampal glutamate levels. Symptom severity was assessed using the Positive and Negative syndrome scale (PANSS) 60mins before drug administration (T1, pre scan), and 270mins after drug administration (T2, post scan). Effects of CBD on left hippocampal glutamate levels, symptoms, and correlations between hippocampal glutamate and symptoms were investigated. Results Compared to placebo, there was a significant increase in left hippocampal glutamate in the psychosis patients under CBD treatment (z= -1.80; p=0.035). Under placebo treatment, change in positive psychotic symptoms (as indexed using the T1 minus T2 PANSS positive symptoms subscale scores) was directly correlated with left hippocampal glutamate levels (rho= 0.69, p=0.004), such that symptoms increased as hippocampal glutamate levels decreased. This significant relationship was not observed under the CBD treatment (rho= 0.102, p=0.72). Discussion This suggests that positive psychotic symptoms may be driven by abnormal hippocampal glutamate concentration, which is sensitive to modulation by CBD. These findings are in keeping with the purported antipsychotic effects of CBD in psychosis, and provide novel insight into the neurochemical interactions underlying these effects.

Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale—supportive analyses from a Phase 3 study

CNS Spectrums ◽  
2017 ◽  
Vol 23 (4) ◽  
pp. 284-290 ◽  
Author(s):  
Leslie Citrome ◽  
Robert Risinger ◽  
Andrew J. Cutler ◽  
Yangchun Du ◽  
Jacqueline Zummo ◽  
...  
Keyword(s):  
Scale Score ◽  
Clinical Global Impression ◽  
Response Rates ◽  
Fixed Dose ◽  
Phase 3 ◽  
General Psychopathology ◽  
Syndrome Scale ◽  
Long Acting ◽  
Post Hoc ◽  
Negative Syndrome

ObjectiveAripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.MethodsPatients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.ResultsOf 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.ConclusionAL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

scholarly journals Nicotine dependence and illness severity in schizophrenia

2012 ◽  
Vol 201 (4) ◽  
pp. 306-312 ◽  
Author(s):  
Rajeev Krishnadas ◽  
Sameer Jauhar ◽  
Susan Telfer ◽  
Somashekara Shivashankar ◽  
Robin G. McCreadie
Keyword(s):  
Nicotine Dependence ◽  
Social Adjustment ◽  
Symptom Severity ◽  
Clinical Symptoms ◽  
Cross Sectional ◽  
Syndrome Scale ◽  
Never Smokers ◽  
Negative Syndrome ◽  
The Relationship ◽  
Higher Doses

BackgroundReasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings.AimsTo examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia.MethodCross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland.ResultsSmokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild–moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers.ConclusionsOur findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.

scholarly journals Brain-Derived Neurotropic Factor Serum Level and Severity Symptom of Bataknese Male Patients with Schizophrenia in North Sumatera, Indonesia

2019 ◽  
Vol 7 (12) ◽  
pp. 1957-1961
Author(s):  
Deasy Hendriati ◽  
Elemeida Effendy ◽  
Mustafa Mahfud Amin ◽  
Vita Camellia ◽  
Muhammad Surya Husada
Keyword(s):  
Serum Level ◽  
Negative Correlation ◽  
Symptom Severity ◽  
Negative Symptoms ◽  
Chronic Schizophrenia ◽  
Serum Levels ◽  
Cross Sectional ◽  
Syndrome Scale ◽  
Male Patients ◽  
Negative Syndrome

BACKGROUND: Schizophrenia is a severe mental disorder that is multi-causative and multi-factor, generally affecting about 1% of the population. The elevation level of brain-derived neurotrophic factor (BDNF) offers several protections from other neurodegenerative processes that occur in schizophrenia since this deficit of neurotrophic factors can contribute to changes in brain structure and function that underlie the schizophrenia psychopathology.AIM: To analyse the correlation between BDNF serum levels and symptom severity by using the Positive and Negative Syndrome Scale (PANSS) instrument in Bataknese male patients with schizophreniaMETHODS: This study was a correlative analytical study with a cross-sectional approach using the Positive and Negative Syndrome Scale (PANSS) instrument to assess symptom severity with 60 subjects of Bataknese male patients with chronic schizophrenia. Moreover, this research was conducted at the Psychiatric Hospital of Prof. Dr M. Ildrem Medan, Indonesia. BDNF serum was analysed with the Quantitative sandwich enzyme immunoassay technique by via Quantikine ELISA Human CXCL8/IL-8 HS. Also, the data analysis was performed through Spearman's correlative bivariate analytics using SPSS software.RESULTS: A negative correlation between the BDNF serum level and the negative scale PANSS score in men with schizophrenia (r = -0.820, p < 0.001) was found. Moreover, there is a negative correlation between BDNF serum levels and PANSS total scores in men with schizophrenia (r = -0.648, p < 0.001)CONCLUSION: BDNF serum level in Bataknese male patients with schizophrenia has a relationship that affects the severity of symptoms in schizophrenic patients, especially for negative symptoms.

scholarly journals The Relationship Between Serum Cytokine Levels and the Degree of Psychosis and Cognitive Impairment in Patients With Methamphetamine-Associated Psychosis in Chinese Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Xue Yang ◽  
Hui Zhao ◽  
Xuebing Liu ◽  
Qin Xie ◽  
Xiaoliang Zhou ◽  
...  
Keyword(s):  
Negative Relationship ◽  
Serum Levels ◽  
Chinese Patients ◽  
Psychotic Symptoms ◽  
Delayed Recall ◽  
Syndrome Scale ◽  
Cytokine Levels ◽  
Function Impairment ◽  
Negative Syndrome ◽  
The Relationship

Background: Cytokine levels can be changed in methamphetamine (METH) use disorders (MUDs) and primary psychosis. The present study assessed serum levels of some kinds of interleukins (ILs) in METH-associated psychosis (MAP) and their relationships with psychotic symptoms and cognitive dysfunction.Methods: Serum IL-2R, IL-6, IL-8, and IL-10 levels were examined by chemiluminescence assays in MAP patients (n = 119) and healthy controls (n = 108). The Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MOCA) were administered.Results: Serum levels of IL-6 and IL-8 were significantly increased in MAP patients (all p &lt; 0.05). There was a negative relationship between IL-2R levels and PANSS positive (P) subscale scores (r = −0.193, p = 0.035). IL-6, IL-8 and IL-10 levels were all negatively correlated with the naming, delayed recall and orientation subscores on the MOCA (r = −0.209, p = 0.022; r = −0.245, p = 0.007; r = −0.505, p &lt; 0.001, respectively).Conclusions: Our results indicate that immune disturbances are related to MAP and that IL-2R, IL-6, IL-8, and IL-10 are associated with the severity of psychotic symptoms and cognitive function impairment.

Facial and vocal markers of schizophrenia measured using remote smartphone assessments (Preprint)

2020 ◽  
Author(s):  
Isaac Galatzer-Levy ◽  
Anzar Abbas ◽  
Vidya Koesmahargyo ◽  
Vijay Yadav ◽  
Mercedez Perez-Rodrigueq ◽  
...  
Keyword(s):  
Symptom Severity ◽  
Clinical Implications ◽  
Clinical Assessments ◽  
Syndrome Scale ◽  
Measurement Tools ◽  
Experimental Laboratory ◽  
Vocal Acoustics ◽  
Vocal Intensity ◽  
Negative Syndrome ◽  
Facial Expressivity

BACKGROUND Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis and severity. Here, we determine their accuracy when acquired through automated assessments conducted remotely through smartphones. Demonstrating utility and validity of remote and automated assessments conducted outside of controlled experimental settings can facilitate scaling such measurement tools to aid in risk assessment and tracking of treatment response in difficult to engage populations. OBJECTIVE We aim to assess the accuracy of these facial and vocal markers through remote assessments and compare them with traditional clinical assessments of schizophrenia severity. METHODS Measurements of facial and vocal characteristics including facial expressivity, vocal acoustics, and speech prevalence were assessed in 20 schizophrenia patients over the course of 2 weeks in response to two classes of prompts previously utilized in experimental laboratory assessments: evoked prompts, where subjects are guided to produce specific facial expressions and phonations, and spontaneous prompts, where subjects are presented stimuli in the form of emotionally evocative imagery and asked to freely respond. Facial and vocal measurements were assessed in relation to schizophrenia symptom severity using the Positive and Negative Syndrome Scale. RESULTS Vocal markers including speech prevalence, vocal jitter, fundamental frequency, and vocal intensity demonstrated specificity as markers of negative symptom severity while measurement of facial expressivity demonstrated itself as a robust marker of overall schizophrenia severity. CONCLUSIONS Established facial and vocal measurements, collected remotely in schizophrenia patients via smartphones in response to automated task prompts, demonstrated accuracy as markers of schizophrenia severity. Clinical implications are discussed.

Effect of l-theanine on glutamatergic function in patients with schizophrenia

2015 ◽  
Vol 27 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Miho Ota ◽  
Chisato Wakabayashi ◽  
Noriko Sato ◽  
Hiroaki Hori ◽  
Kotaro Hattori ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Pittsburgh Sleep Quality Index ◽  
Chronic Schizophrenia ◽  
Antipsychotic Treatment ◽  
Resonance Spectroscopy ◽  
Syndrome Scale ◽  
Before And After ◽  
Negative Syndrome ◽  
The Brain ◽  
Chemical Mediators

ObjectivesGlutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that l-theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of l-theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS).MethodThe subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. l-Theanine (250 mg/day) was added to the patients’ ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results.ResultsThere were significant improvements in the PANSS positive scale and sleep quality after the l-theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week l-theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by l-theanine.ConclusionsOur results suggest that l-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that l-theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect.

Palmitate de palipéridone à doses flexibles chez des patients non-aigus atteints de schizophrénie après échec d’un autre traitement par antipsychotiques injectables à action prolongée

2013 ◽  
Vol 28 (S2) ◽  
pp. 107-108
Author(s):  
P. Cherubin ◽  
L. Hargater ◽  
B. Bergmans ◽  
A. Bjorner ◽  
H. Knegtering ◽  
...  
Keyword(s):  
Scale Score ◽  
Social Performance ◽  
Syndrome Scale ◽  
Negative Syndrome ◽  
Performance Scale

ObjectifsÉvaluer la tolérance, la sécurité d’emploi et la réponse à un traitement par palmitate de palipéridone (PP) à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par un autre antipsychotique injectable à action prolongée : décanoate d’halopéridol (Déc-Hal), décanoate de flupentixol (Déc-Fpt), décanoate de fluphénazine (Déc-Flu), zuclopenthixol (Zuc) ou rispéridone à libération prolongée (RIS-LP).MéthodesÉtude internationale, prospective, ouverte, de six mois, chez des patients atteints de schizophrénie, non aigus mais insuffisamment contrôlés par d’autres antipsychotiques injectables à action prolongée.Critères d’évaluationTaux de réponse (amélioration ≥ 20 % du score total à la PANSS [Positive and Negative Syndrome Scale]), score à la PSP (Personal and Social Performance scale), événements indésirables (EIs).RésultatsLes analyses ont été réalisées sur la population en intention de traiter de façon stratifiée pour chaque traitement : 53 patients Déc-Hal, 35 Déc-Fpt, 44 Déc-Flu, 42 Zuc, 56 RIS-LP. Les scores totaux moyens à la PANSS initiale variaient de 67,7 ± 20,3 [RIS-LP] à 75,7 ± 13,2 [Déc-Hal]. Entre 71,4 % [RIS-LP] et 85,7 % [Déc-Fpt] des patients ont terminé l’étude. À la fin de l’étude, 53,7 % [Zuc], 54,7 % [Déc-Hal], 59,1 % [Déc-Flu], 61,1 % [RIS-LP] et 61,8 % [Déc- Fpt] des patients ont vu leur score total à la PANSS diminuer d’au moins 20 %. Les scores moyens de PSP de base étaient de 48,7 [Déc-Hal], 59,6 [Déc-Fpt], 53,5 [Déc-Flu], 52,9 [Zuc] et 60,1 [RIS-LP], et le changement en fin d’étude était respectivement de : 5,2 ; 6,1 ; 6,0 ; 6,4 ; et 5,2 (p ≤ 0,0163 pour tous les traitements). Les EIs rapportés au moins une fois dans tous les sous-groupes : douleur au site d’injection, insomnie, trouble psychotique.ConclusionsLe PP à doses flexibles a été bien toléré et a permis une réponse thérapeutique cliniquement significative chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par d’autres antipsychotiques injectables à action prolongée.

scholarly journals The Difference in Negative Scale Score Measured with Positive and Negative Syndrome Scale in Schizophrenic Male Patient Treated with Risperidone in Addition to Vitamin E and Treated with Risperidone Alone at Prof. Dr. M. Ildrem Mental Hospital Medan

2021 ◽  
Vol 9 (T3) ◽  
pp. 104-107
Author(s):  
Risni Nanda ◽  
Elmeida Effendy ◽  
Mustafa Mahmud Amin
Keyword(s):  
Vitamin E ◽  
Scale Score ◽  
Mental Hospital ◽  
Syndrome Scale ◽  
Significant Difference ◽  
Post Test ◽  
Male Patients ◽  
The Difference ◽  
Negative Syndrome ◽  
Risperidone Treatment

OBJECTIVES: The objectives of the study were to investigate the difference in negative scale score in schizophrenic male patients that received vitamin E-fortified risperidone and those receiving risperidone treatments alone. METHODS: This study was a pre- and post-test experimental design which compared two groups; a group of men with schizophrenia who were given risperidone treatment with added Vitamin E and another group of men with schizophrenia who were given only risperidone treatment. The study was conducted at the outpatient clinic of Prof.dr. M. Ildrem Mental Hospital Medan, North Sumatra within August to November 2019. The study has been approved by the Research Ethics Committee of the Faculty of Medicine, North Sumatera University. The instrument used to assess negative scale on the subjects is PANSS. RESULTS: We found that statistical analysis using corrected Mann–Whitney U-test obtained p < 0.001 (p < 0.05). CONCLUSIONS: There was a strongly significant difference in negative scale Positive and Negative Syndrome Scale (PANSS) scores on 4th and 8th weeks in the group which received risperidone treatment with additional Vitamin E compared to the other group that received risperidone alone.

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