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OBJECTIVE: There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes. METHODS: Retrospective analyses from the naturalistic, longitudinal, multicentre, "Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)" Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory. RESULTS: FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N=56) had more sleep disturbances (42.9% vs 18.8%, P=0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P=0.007) than FEP with no substance use (N=70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P=0.015), perceptual abnormalities (46.4% vs 67.4%, P=0.006), hallucinations (55.4% vs 71.5%, P=0.029), and disorganised thinking (41.1% vs 61.1%, P=0.010) than FEP group with previous tobacco and cannabis use (N=144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean=23.73years [SD=5.09]) versus those with tobacco use only (mean=26.21 [SD=4.80]) (P=0.011). CONCLUSIONS: The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis. This study received economic support from the Spanish Ministry of Economic Affairs and Competitiveness, the Carlos III Health Care Insti-tute (Grant Number PI11/00325, PI14/00612), the European Regional Development Fund, the European Union, “Una manera de hacer Europa/ A Way of Shaping Europe”, and CIBERSAM.

[EN] Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group. This work was supported by grants from the Spanish Ministries of Health-ISCIII (FIS PI13/01102) and MICINN-FEDER Funds (SAF2016-75500-R and PID2019-109033RB-I00) to JCL and by CIBERSAM. JRC is a Ramon y Cajal Researcher (Spanish Ministry of Science and Innovation and FEDER). JdD-A was supported by the Catalan Intensification Programme (PERIS, SLT008/18/00092; Generalitat de Catalunya).

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes. © 2020 The Author(s).

AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

International audience; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

The novel coronavirus disease (COVID-19) pandemic has brought a great deal of pressure for medical students, who typically show elevated anxiety rates. Our aim is to investigate the prevalence of anxiety in medical students during this pandemic. This systematic review and mini meta-analysis has been conducted following the PRISMA guidelines. Two researchers independently searched PubMed on 26 August 2020 for cross-sectional studies on medical students during the COVID-19 outbreak, with no language restrictions applied. We then performed a manual search to detect other potentially eligible investigations. To the 1361 records retrieved in the initial search, 4 more were added by manual search on medRxiv. Finally, eight studies were finally included for qualitative and quantitative analysis, which yielded an estimated prevalence of anxiety of 28% (95% CI: 22–34%), with significant heterogeneity between studies. The prevalence of anxiety in medical students is similar to that prior to the pandemic but correlates with several specific COVID-related stressors. While some preventive and risk factors have been previously identified in a non-pandemic context, knowledge and cognitions on COVID-19 transmission, treatment, prognosis and prevention negatively correlate with anxiety, emerging as a key preventive factor that may provide a rationale for why the levels of anxiety have remained stable in medical students during the pandemic while increasing in their non-medical peers and the general population. Other reasons for the invariability of anxiety rates in this population are discussed. A major limitation of our review is that Chinese students comprised 89% the total sample, which could compromise the external validity of our work.

AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study. © 2020 Elsevier B.V.