Increased markers of inflammation after cannabis cessation and their association with psychotic symptoms.

INTRODUCTION: A dysbalance of the immune system in psychotic disorders has been well investigated. However, despite a higher prevalence of cannabis (THC) consumption in patients with psychosis, few studies have investigated the impact of this use on inflammatory markers. METHODS: One hundred and two inpatients were included in this retrospective study. Leukocytic formula, hsCRP, fibrinogen levels and urinary THC were measured, and comparisons were performed at baseline and after 4 weeks of cannabis cessation between cannabis users (THC+) and non-users (THC-). RESULTS: After cannabis cessation, we found a greater increase in leucocyte level (p < 0.01), monocyte level (p = 0.05) and a statistical trend to a highest increase of lymphocyte level (p = 0.06) between baseline and 4 weeks in the THC+ group as compared to the THC- group. At 4 weeks, highest leucocyte (p = 0.03), lymphocyte (p = 0.04) and monocyte (p < 0.01) counts were found in the THC+ group, whereas at baseline no difference was found. A positive correlation was found between monocyte count at 4 weeks and baseline Positive and Negative Syndrome Scale (PANSS) negative subscore (p = 0.045) and between the variation of monocyte count between baseline and 4 weeks and the PANSS total score at 4 weeks (p = 0.05). CONCLUSION: THC cessation is associated with an increase in inflammatory markers, including white blood cell, lymphocyte and monocyte levels, which correlates with symptomatology of patients with psychosis.

Reduction of alcohol use and increase in psychological flexibility after a naturalistic psychedelic experience: a retrospective survey.

INTRODUCTION: Alcohol use can be significantly associated with negative social, professional, and health outcomes. Even more so, alcohol use disorder (AUD) is a critical public health issue and major avoidable risk factor. This study aimed to examine the effect of a naturalistic psychedelic experience on alcohol use and related measures. METHODS: A retrospective online survey was conducted on 160 individuals who reported a psychedelic experience and a concomitant drinking habit but did not necessarily have an AUD. Demographic data, characteristics of the psychedelic experience, and changes in alcohol consumption and psychological flexibility were surveyed. Results: The mean number of drinking days per week and AUDIT scores significantly decreased after the psychedelic experience (P < .001). Subjects who quit or reduced drinking had a more severe AUD (P < .01) and lower psychological flexibility (P = .003) before the psychedelic session. Alcohol use reduction was significantly associated with the intensity of the mystical experience (P = .03). Psychological flexibility increased more in participants who reduced their alcohol use (P < .001), and the change in psychological flexibility was one of the predictors of alcohol use improvement (P = .003). Conclusion: Our findings suggest that a naturalistic psychedelic experience could be associated with a reduction in alcohol use and dependency. Such positive health outcomes can be associated with the intensity of the mystical experience as well as an increase in psychological flexibility.

Impact of the COVID-19 pandemic on the infectious disease epidemiology.

Introduction: COVID-19 pandemic has exerted a huge impact on different aspects of public health. Mandatory notifications are a fundamental tool to have a general picture of infection disease spread in a population. The aim of this study was to evaluate the impact the COVID-19 pandemic had on infectious disease epidemiology. Methods: We collected and analyzed all the infectious disease notifications made in the pre-pandemic (2017-2019) and the pandemic (2020-2022) three-years periods in the provincial territory of Messina, Italy. Results: The total number of notifications significantly decreased by 41% in the pandemic period compared to the pre-pandemic one, with very high reduction of certain disease notifications such as measles and varicella. Similarly, other airborne infections, such as meningococcal meningitis and tuberculosis, underwent an important decrease. Conversely, an increase was found for some infections such as syphilis and, especially, scabies that reported a percentage value of +159.9%. Conclusions: The COVID-19 pandemic, reducing the possibility of microbial spread following to the lockdown and, in addition, to the constant use of face masks and other personal protective equipment, the frequent hand-washing, more ventilation of the living locals, and less gathering, surely reduced the occasions and the possibility to get many infections. On the other hands, the pandemic had a negative impact on scabies diffusion probably due to different causes among which the worsening of some poor realities, the restrictions that forced people to live in strict contact and, especially, the worsening of the conditions of the elderly living in care homes.

The Modulated Role of Toxoplasma gondii on Eosinophils in Psychiatric Disorders after Cannabis Cessation.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (EOS), the eosinophil-to-lymphocyte ratio (ELR), and the eosinophil-to-neutrophil-to-lymphocytes ratio (ENLR) before and after cannabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were included in the study. T. gondii, EOS, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest levels and increase of PNE (p = 0.02), ENLR levels (p = 0.031) and highest level of ELR (p = 0.03) were found in patients after cannabis cessation only in patients positive for T. gondii serology (Toxo+ group). At four weeks, significant interactions between cannabis and T. gondii status for EOS (p = 0.038), and for ENLR (p = 0.043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = 0.049). After cannabis cessation, we found a positive correlation between negative symptoms and EOS levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patients after cannabis cessation.

White blood cells and patients with psychiatric disorders needing seclusion: A retrospective non-interventional study.

OBJECTIVE: The objective of this retrospective study was to investigate the peripheral immunological markers using leucocyte count, the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) in patients with aggressive behavior, during and after seclusion. METHODS: Ninety-nine inpatients were included in this retrospective study. Leucocyte count was measured, and NLR, PLR and MLR were calculated and compared between a group of patients who required seclusion and a group who did not. A multivariate analysis was performed using binary logistic regression, including confounding factors such as age, gender, medication, BMI, smoking status and diagnosis. RESULTS: We found the lowest levels of lymphocytes (P=0.01) and basophils (P<0.01) and the highest NLR (P=0.02) and MLR (P=0.04) in the seclusion group. We also found a restoration of these parameters after the end of the seclusion period. Furthermore, we found a positive correlation between the PANSS negative subscore, and PLR (P=0.05), or MLR (P=0.03) after seclusion, and between the MLR variation across the seclusion period and the PANSS general subscore after the end of seclusion (P=0.04). CONCLUSION: This study shows that NLR and MPR are higher in patients with aggressive symptoms and/or agitation who require seclusion. These immunological markers could be considered as state markers.

Caudate gray matter volumes and risk of relapse in Type A alcohol-dependent patients: A 7-year MRI follow-up study.

Background: Whether alteration in regional brain volumes can be detected in Type A alcoholics both at baseline and after a long follow-up remains to be confirmed. Therefore, we examined volume alterations at baseline, and longitudinal changes in a small follow-up subsample. Methods: In total of 26 patients and 24 healthy controls were assessed at baseline using magnetic resonance imaging and voxel-based morphometry, among which 17 patients and 6 controls were re-evaluated 7 years later. At baseline, regional cerebral volumes of patients were compared to controls. At follow-up, three groups were compared: abstainers (n = 11, more than 2 years of abstinence), relapsers (n = 6, <2 years of abstinence), and controls (n = 6). Results: The cross-sectional analyses detected, at both times, higher caudate nuclei volumes bilaterally in relapsers compared to abstainers. In abstainers, the longitudinal analysis indicated recovery of normal gray matter volumes in the middle and inferior frontal gyrus, and in the middle cingulate, while white matter volumes recovery was detected in the corpus callosum and in anterior and superior white matter specific regions. Conclusions: Overall, the present investigation revealed larger caudate nuclei in the relapser AUD patient group both at baseline and at follow-up in the cross-sectional analyses. This finding suggest that a higher caudate volume could be a candidate risk factor of relapse. In patients with specific type A alcohol-dependence, we showed that long-term recovery in fronto-striato-limbic GM and WM volumes occurs during long-term abstinence. These results support the crucial role of frontal circuitry in AUD.

Validation of a French Version of the Mystical Experience Questionnaire with Retrospective Reports of the Most Significant Psychedelic Experience among French Users.

Mystical experiences triggered by psychedelic drugs predict symptom reduction in various psychiatric disorders, and increased well-being in healthy individuals. This work aimed at validating a French version of a tool used to measure mystical experiences: the Revised Mystical Experience Questionnaire-30 items (MEQ30). Construct validity, internal consistencies, concurrent, discriminant, and predictive validities of the French MEQ30 were examined using data about the most significant psychedelic experience of 320 French individuals. Results showed that the original four-factor (i.e., mystical, positive mood, transcendence, and ineffability) structure fit the data best, with good to excellent statistical indices. Total French MEQ30 score was strongly associated with subjective ratings of the mystical (i.e., mystical, spiritual, or religious, and personally significant) and drug intensity-related qualities of the experience, but not with non-mystical (i.e., fun, inebriating, and easy) qualities. Moreover, French MEQ30 score was a significant predictor of subjective positive changes in psychological well-being, relations with self and others, feeling of proximity or connection with nature, and creativity, whereas drug intensity-related and non-mystical qualities of the experience were not, or were only weakly associated with such changes. This French version of the MEQ30 seems to be an appropriate tool for measuring mystical experiences among French speaking individuals.

Impact of cannabis use and its cessation on the dosage and the efficacy of antipsychotic drugs in in- and outpatients with schizophrenia taking medication: A systematic review and meta-analysis.

Compared with the general population, there are more cannabis users among patients suffering from schizophrenia and this consumption seems to impact the course and the treatment of their pathology. The aim of this meta-analysis and systematic review was to assess the impact of cannabis use on the efficacy of treatments, more particularly regarding the antipsychotic dosage, symptoms evolution, therapeutic resistance and the risk of relapse in patients with schizophrenia taking medication. We performed a systematic search of keywords on multiple databases up to August 2020 to identify all studies meeting the following criteria: comparison between cannabis smokers and non-cannabis users in patients with schizophrenia, assessment of antipsychotics doses, information about their efficacy or resistance to treatment and control of the compliance. Standardized mean differences were calculated for antipsychotic dosage and symptoms evolution at discharge, and a systematic review was performed for other outcomes. Twelve studies were included. Cannabis use did not seem to be associated with higher doses of antipsychotics at seven days and at the end of the studies, nor with poorer symptoms evolution, and nor with higher rate of antipsychotic resistance. However, cannabis use seems to be associated with a higher risk of relapse. This meta-analysis provides evidence that previous cannabis use, or occasional use, in patients with schizophrenia taking medication does not impact antipsychotic efficacy as described by antipsychotic dosage or PANSS score.

Cannabis Cessation, Inflammatory Markers and Schizophrenia.

Objective A dysbalance of the immune system in schizophrenia has been largely described but few studies have investigated the impact of cannabis use on inflammatory markers in patients with schizophrenia. The objective of our study was to investigate the impact of cannabis use on high-sensitivity C-reactive protein (hsCRP), fibrinogen levels and leucocytic formula in patients with schizophrenia. Methods: Thirty-eight acutely ill inpatients with schizophrenia were included. Patient hsCRP, fibrinogen levels, leukocytic formula and urinary cannabis were measured at baseline and after four weeks of treatment. Results: After four weeks of cannabis cessation (as confirmed by urinary tests), we found an increase of hsCRP level (p = .016) and lymphocytes (p = .03) in consumers patients whereas no difference was observed in non-consumers patients. As compared to non-consumers patients with schizophrenia, consumers had lower levels of hsCRP (p = .045). Finally, a negative correlation was found between the PANSS score evolution (between baseline and 4 weeks) and baseline hsCRP level. Conclusions: In our study, cannabis cessation raises inflammatory markers though improving clinical symptoms. The investigation and the understanding of interactions between cannabis use and inflammatory markers in patients with schizophrenia is of importance and could in the future be a new target for treatment of psychiatric symptoms linked to inflammation.

Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review.

BACKGROUND: The use of psychedelic treatments has shown very promising results in some psychiatric and addictive disorders, but not all patients achieved a response. AIM: The aim of this review is to explore the clinical and biological factors which could predict the response to psychedelics in psychiatric and addictive disorders. METHODS: A systematic research was performed on MEDLINE, PsycInfo, Web of science, and Scopus databases from January 1990 to May 2020. All studies investigating the predictive factors of response to psychedelics regardless of psychiatric or addictive disorders, were included. RESULTS: Twenty studies investigating addictive disorder, treatment-resistant depression, obsessive-compulsive disorder and depressive and anxiety symptoms in patients with life-threatening cancer were included in this review. We found that, in all indications, the main predictive factor of response to psychedelics is the intensity of the acute psychedelic experience. Indeed, we found this factor for alcohol and tobacco use disorders, treatment-resistant depression, and anxiety and depressive symptoms in patients with life-threatening cancer, but not for obsessive-compulsive disorder. CONCLUSION: The intensity of the acute psychedelic experience was the main predicting factor of response. The action mechanism of this experience was not clear, but some hypotheses could be made, such as a modulation of serotoninergic system by 5-HT2A receptors agonism, a modulation of the default mode network (DMN) with an acute modular disintegration of the DMN followed by a re-integration of this network with a normal functioning, or an anti-inflammatory effect of this treatment.

Chronic smoking and cognition in patients with schizophrenia: A meta-analysis.

BACKGROUND: Patients with schizophrenia display a very high rate of smoking in comparison with the general population. The aim of the present meta-analysis was to assess the association between cognitive performances and smoking status in patients with schizophrenia. METHODS: This review was registered at PROSPERO, number CRD42019126758. After a systematic search on MEDLINE, PsycINFO, and clinicaltrials.gov databases, all studies measuring neurocognitive performances in both smoking and nonsmoking patients with a diagnosis of schizophrenia were included. Original data were extracted. Standardized mean differences (SMD) were calculated with the means and standard deviations extracted using a random-effect model. Cognitive performances were compared between smoking and nonsmoking patients with schizophrenia. Meta-regressions were performed to explore the influence of sociodemographic and clinical variables on SMD. RESULTS: Eighteen studies were included in this meta-analysis. Chronic smoking in patients with schizophrenia, compared to nonsmoking, was associated with a significant more important impairment in attention (p = 0.02), working memory (p < 0.001), learning (p < 0.001), executive function (EF) reasoning/problem solving (p < 0.001) and speed of processing (p < 0.001), but not in delayed memory, EF abstraction/shifting, EF inhibition and language. The meta-regression analysis found that attention impairment could be influenced by age (p < 0.001) and Positive and Negative Syndrome Scale (PANSS) total score (p = 0.006). CONCLUSIONS: This meta-analysis provides strong evidence that, in patients with schizophrenia, chronic smoking is related to cognitive impairment. This association emphasizes the importance of paying careful attention to both tobacco addiction and cognitive functioning in patients with schizophrenia.

Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis.

BACKGROUND: Psychedelic drugs have shown an efficacy in some psychiatric disorders and have an original mechanism of action with a 5-HT2A agonism. AIM: The aim of this meta-analysis was to assess by a quantitative analysis the putative efficacy of psychedelic drugs on depressive symptoms and to investigate the kinetic of this efficacy. METHODS: We searched the MEDLINE and PsycINFO databases through April 2019, without limits on year of publication. Means and standard deviations were extracted to calculate standardized mean differences (SMD). Scores of depressive symptoms were compared with baseline scores at days 7, 14, and 21; weeks 4-5 and 6-8; and months 3 and 6. RESULTS: Eight studies were included in this meta-analysis. A significant decrease of depressive symptoms was found from day 1 (n = 5 studies; SMD = ‒1.4, 95% confidence interval (CI): ‒2.33 to ‒0.48, p = 0.003) to 6 months (n = 4 studies; SMD = ‒1.07, 95% CI: ‒1.44 to ‒0.7, p < 0.001) after psychedelic sessions. No serious adverse effect was reported in all included studies. A transient increase of the heart rate, blood systolic, and diastolic pressure were found after psychedelics compared with placebo. CONCLUSION: This meta-analysis shows that psychedelic treatments were safe and could contribute to a rapid improvement of depressive symptoms.

Magnetic resonance spectroscopy studies in subjects with high risk for psychosis: A meta-analysis and review.

INTRODUCTION: Even though anomalies on brain metabolites have been found in schizophrenia, researches about subjects with high risk (HR) show heterogeneous results. Thus, this meta-analysis aims to characterize the metabolic profile of HR subjects, first, compared to controls (HC) and then compared to people with schizophrenia. METHODS: After a systematic database search, means and standard deviations were extracted to calculate standardized mean differences (SMD). Cerebral metabolites levels were compared between HR subjects and HC or patients with schizophrenia in all regions of interest investigated in included studies. Meta-regressions were performed to explore the influence of demographic and clinical variables on metabolites level's SMDs. RESULTS: Thirty-nine studies were included in this meta-analysis. A higher level of glutamine + glutamate (Glx) was found in the medial prefrontal cortex (mPFC) (p < 0.01) and potentially in the basal ganglia (p = 0,05) as well as a higher level of myo-inositol (mI) in the dorsolateral prefrontal cortex (DLPFC) (p = 0.04) in HR subjects compared to HC. A higher level of choline (Cho) was found in people with schizophrenia compared to HR subjects in the DLPFC (p < 0.001) and the medial temporal lobe (p = 0.02). Meta-regression analyses showed negative associations between SMD for Cho concentration, the percentage of females or the age (p = 0.01). CONCLUSIONS: The present meta-analysis provides evidence that some brain metabolites concentrations are disrupted before the transition to psychosis and could be considered like a vulnerability.

Kinetics of Cytokine Levels during Antipsychotic Treatment in Schizophrenia: A Meta-Analysis.

Background: Immune system dysfunction is a hypothesis in the psychopathology of schizophrenia, but the impact of antipsychotic treatment within this system is not clear. The aim of this meta-analysis was to investigate the impact of antipsychotic treatment on cytokine levels in in vivo studies on schizophrenia. Methods: After a systematic database search, original data were extracted with the help of certain authors. Means and SDs were extracted to calculate standardized mean differences. Cytokine levels were compared in vivo in schizophrenia patients, before and after antipsychotic treatment. Meta-regressions were performed to explore the influence of demographic and clinical variables on cytokine level standardized mean differences. Stratifications by treatment and diagnosis were also performed. Results: Forty-seven studies were included in this meta-analysis. Proinflammatory cytokine level decreases were found for interleukin-1 ß levels (P<.0001) and interferon-γ (P=.01) and a statistical trend towards a decrease in interleukin-6 (P=.08) and tumor necrosis factor-α (P=.07) levels. An antiinflammatory cytokine level increase was found for soluble tumor necrosis factor-R2 (P<.001) and soluble interleukin 2-R (P=.03) levels. A meta-regression analysis found a correlation between interleukin-6 level standardized mean differences and positive schizophrenia symptom score standardized mean differences before and after treatment (P=.01). Stratification by diagnosis or treatment found a possible impact of the kinetics of cytokine levels. Conclusions: The present meta-analysis provides evidence that antipsychotic treatment has an antiinflammatory effect and could normalize immune balance dysfunction in schizophrenia. Interleukin-6 level normalization could be a marker of illness equilibration and thus used in clinical practice.

Meta-analysis and review of dopamine agonists in acute episodes of mood disorder: Efficacy and safety.

The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3.00; P = 0.05), but not for low-dose aripiprazole. In bipolar depression, no improvement of remission and response rates was found for aripiprazole in monotherapy, whereas improved response rate (OR: 10.27, P < 0.01) was found for pramipexole only as an add-on to another mood stabilizer. In major depressive disorder, relatively similar improvements of remission rates were found for high-dose (OR: 1.96, p < 0.01) and low-dose aripiprazole (OR: 1.68, P = 0.01), as well as brexpiprazole (OR: 1.52, P = 0.05) as an add-on to antidepressant medication. Our meta-analysis shows that partial dopamine agonists at high doses are effective in treating acute mania. In major depressive disorder, which is resistant to classical antidepressants, low doses of partial dopamine agonists as adjunct therapy may represent a relatively safe and effective alternative.

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression.

BACKGROUND: Many studies have measured central and peripheral γ-aminobutyric acid (GABA) levels in patients with depression. We performed a meta-analysis to provide an objective overview of GABA changes in those with unipolar or bipolar depression. METHODS: After a systematic database search, original data were extracted with the help of seminal authors to calculate standardized mean differences. We compared GABA levels between patients with current major depressive episodes and controls, between euthymic patients and controls, and in patients before and after treatment. We performed meta-regressions to explore the influence of demographic and clinical variables on GABA significant mean differences. RESULTS: For unipolar depression, central and peripheral GABA levels were diminished in currently depressed patients, but normal in euthymic patients, compared with the healthy controls. For bipolar disorder, GABA levels were diminished in medication-free patients, but seemed to be normalized in medicated patients, compared with the healthy controls. We found no significant association with demographic or clinical variables. LIMITATIONS: There was a great heterogeneity across studies, probably because of the substantial variation of clinical characteristics in the included samples. Many subanalyses were performed to assess how the diagnosis, medications, or the type of measurements of peripheral or central GABA levels may affect the main results. CONCLUSION: The GABA levels evolved differentially in patients with unipolar and bipolar disorders. Our results suggest that GABA levels could represent a biomarker of symptomatic states in patients with unipolar disorder and would be normalized by mood stabilizers in those with bipolar disorder.

Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression.

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3-4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3-4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.