The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

AIMS: Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample. METHODS: Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of 'Genetic' models (solely fitted with PRS-SZ), 'Environmental' models (solely fitted with each environmental stressor), 'Independent' models (with PRS-SZ and each environmental factor), and 'Interaction' models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models. RESULTS: There were no genes-environment associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. CONCLUSIONS: This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

Cannabis use disorder and dissociation: A report from a prospective first-episode psychosis study.

BACKGROUND: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, the relationship between cannabis use and dissociative symptoms has been scarcely investigated. AIMS: To examine differences in psychotic and dissociative symptoms, and in functioning in first-episode psychotic patients (FEPp) using cannabis compared with those not using cannabis. METHODS: Between January 2014 and December 2019, seventy FEPp with cannabis use disorder (N = 35) and without it (N = 35) were recruited in psychiatric inpatient facilities in the Italian regions of Lazio and Piemonte. All subjects were assessed at FEP, after 4 and 8 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Dissociative Experiences Scale - II (DES-II). Detailed information on the pattern of cannabis and other substance use were collected. RESULTS: FEP using cannabis showed higher levels of positive symptomatology, dissociative experiences and worse functioning than their non-user counterpart, despite a comparable antipsychotic treatment. At an eight-month prospective evaluation, FEP using cannabis still showed higher levels of positive symptomatology and dissociation. Moreover, global functioning worsened over time in FEPp using cannabis, whereas it improved those not using it. DISCUSSION: Our findings suggest that a greater degree of dissociation and positive symptoms at FEPp and their persistence over time may characterise cannabis-associated psychosis. Both these factors might explain the overall functioning worsening over time that we observed in the cannabis-user group compared to the functioning improvement in the non-user group.

Surgical activity during the Covid-19 pandemic: Results for 112 patients in a French tertiary care center, a quality improvement study.

BACKGROUND: After the emergence of Covid-19 in China, Hubei Province, the epidemic quickly spread to Europe. France was quickly hit and our institution was one of the first French university to receive patients infected with Sars-COV2. The predicted massive influx of patients motivated the cancellation of all elective surgical procedures planned to free hospitalization beds and to free intensive care beds. Nevertheless, we should properly select patients who will be canceled to avoid life-threatening. The retained surgical indications are surgical emergencies, oncologic surgery, and organ transplantation. MATERIAL AND METHODS: We describe the organization of our institution which allows the continuation of these surgical activities while limiting the exposure of our patients to the Sars Cov2. RESULTS: After 4 weeks of implementation of intra-hospital protocols for the control of the Covid-19 epidemic, 112 patients were operated on (104 oncology or emergency surgeries and 8 liver transplants). Only one case of post-operative contamination was observed. No mortality related to Covid-19 was noted. No cases of contamination of surgical care personnel have been reported. CONCLUSION: We found that the performance of oncological or emergency surgery is possible, safe for both patients and caregivers.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Natural history of Charcot-Marie-Tooth 2: 2-year follow-up of muscle strength, walking ability and quality of life.

Charcot-Marie-Tooth (CMT) disease is the most frequent inherited neuropathy, no therapies are available at the moment but clinical trials are ongoing. For that reason it is very important to know the natural history of the disease. We report the results of the natural history of clinical features and quality of life (QoL) in patients with CMT2. Twenty patients were enrolled. At recruitment and at follow-up (2 years), all patients underwent neurological evaluation, QoL and disability assessments. The study-end evaluation took place 20-28 months after the baseline evaluation. During the 2-year follow-up period, CMT2 patients showed a mild reduction of strength of distal muscles of upper limbs and proximal muscles of lower limbs, a worsening sensory function and a mild increase in walking disability. However, there was no relevant worsening of QoL, except for a mild deterioration of one mental health domain.

Alzheimer's disease and anaesthesia: implications for the central cholinergic system.

Alzheimer's disease (AD) is associated with a loss of cholinergic neurons resulting in profound memory disturbances and irreversible impairment of cognitive function. The central cholinergic system is involved in the action of general anaesthetic agents. Anaesthetic modulation of cholinergic transmission has profound effects on brain function via a cascade of synaptic and postsynaptic events by binding both nicotinic and muscarinic receptors. During general anaesthesia, decrease in acetylcholine release and depression of cholinergic transmission facilitates the desirable effects of general anaesthetics, such as loss of consciousness, pain, voluntary movements and memory. From this point of view, patients with AD, characterized by a compromised neuronal transmission, represent particular cases in which the choice of anaesthesia drugs may have a negative effect on the postoperative outcome. A future challenge may be the identification of brain targets of general anaesthetics which do not expose patients to postoperative cognitive dysfunction, nor interfere with prognosis of brain degenerative disease.

Drugs of anesthesia acting on central cholinergic system may cause post-operative cognitive dysfunction and delirium.

Given the progressive and constant increase of average life expectancy, an increasing number of elderly patients undergo surgery. After surgery, elderly patients often exhibit a transient reversible state of cerebral cognitive alterations. Among these cognitive dysfunctions, a state of delirium may develop. Delirium is an aetiologically non-specific syndrome characterised by concurrent disturbances of consciousness and attention, perception, thinking, memory, psychomotor behaviour and the sleep-wake cycle. Delirium appears to occur in 10-26% of general medical patients over 65, and is frequently associated with a significant increase in morbidity and mortality. During hospitalization, mortality rates have been estimated to be 10-26% of patients who developed post-operative delirium, and 22-76% during the following months. Over the last few decades, post-operative delirium has been associated with several pre-operative predictor factors, as well as age (50 years and older), alcohol abuse, poor cognitive and functional status, electrolyses or glucose abnormalities, and type of surgery. The uncertain pathogenesis of post-operative cognitive dysfunctions and delirium has not permitted a causal approach to developing an effective treatment. General anesthesia affects brain function at all levels, including neuronal membranes, receptors, ion channels, neurotransmitters, cerebral blood flow and metabolism. The functional equivalents of these impairments involve mood, memory, and motor function behavioural changes. These dysfunctions are much more evident in the occurrence of stress-regulating transmission and in the alteration of intra-cellular signal transduction systems. In addition, more essential cellular processes, that play an important role in neurotransmitter synthesis and release, such as intra-neuronal signal transduction and second messenger system, may be altered. Keeping in mind the functions of the central muscarinic cholinergic system and its multiple interactions with drugs of anesthesia, it seems possible to hypothesize that the inhibition of muscarinic cholinergic receptors could have a pivotal role in the pathogenesis not only of post-operative delirium but also the more complex phenomena of post-operative cognitive dysfunction.