Les signes révélateurs d’anomalies immuno-inflammatoires au cours des dépressions, des troubles bipolaires, de la schizophrénie ou de l’autisme sont aujourd’hui au premier plan du développement de ...pistes thérapeutiques innovantes. Pour introduire ce nouveau domaine, sera présentée tout d’abord une revue de la littérature sur l’utilisation des anti-inflammatoires en psychiatrie. Guillaume Fond, PH, responsable du centre expert schizophrénie du pôle de psychiatrie du GH Mondor résumera les études sur les anti-inflammatoires comme les COX inhibiteurs, les anti-TNF alpha ou les antibiotiques. La voie des rétrovirus humains endogènes constitue un mécanisme possible d’exploration étiopathogénique des troubles psychotiques majeurs et une voie thérapeutique nouvelle. Hervé Perron (laboratoire GeNeuro, Grenoble) décrira les arguments récemment obtenus en faveur de la réactivation des rétrovirus endogènes, à l’occasion d’infections par des parasites ou des virus, déclenchant une cascade immuno-inflammatoire. L’utilisation d’anticorps spécifiques neutralisant l’enveloppe protéique du rétrovirus endogène est une cible thérapeutique innovante pour la schizophrénie. L’importance des liens entre le tube digestif, et en particulier le microbiote intestinal, et pathologies psychiatriques est depuis peu au cœur de l’exploration des mécanismes causaux et de la découverte de nouvelles thérapeutiques. Michel Neunlist (IMAD-UMR Inserm U 913, Nantes) décrira comment l’étude des interactions entre le microbiote intestinal et le système nerveux digestif ou entérique pourrait permettre de mieux appréhender les interactions entre le microbiote et le cerveau. Il présentera aussi le développement d’outils permettant d’étudier l’unité neuro-glio-épithéliale de l’intestin chez le patient et leur apport à la compréhension des pathologies neurodigestives et neurodégénératives. Enfin, il décrira le développement d’approches thérapeutiques visant à renforcer la barrière épithéliale intestinale (neurostimulation digestive ou nutritionnelle) dans ces pathologies.
Objective
To perform a meta‐analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was ...to analyze factors possibly moderating heterogeneity.
Method
A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed.
Results
A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive–compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant.
Conclusion
These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur.
Introduction
In schizophrenia, abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by
C4
overexpression in various ...brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions relevant to schizophrenia. Moreover, transcriptional studies of genes coding for proteins regulating the Complement system activity are lacking. Furthermore, it remains unknown whether cerebral and peripheral expression of
C4
and Complement control proteins (CCP) are related.
Objectives
To identify altered expression of
C4
and CCP (
CSMD1
,
CSMD2
,
CD46
) coding genes at the cerebral and peripheral levels in schizophrenic individuals.
Methods
We explored
C4
and CCP coding genes expression at the cerebral and peripheral levels. Using
shiny
GEO application we analyzed gene expression from eight Gene Expression Omnibus datasets obtained from 196 schizophrenic individuals and 182 control subjects. First, we compared gene expression between schizophrenic patients and controls in postmortem cerebral samples from 7 different brain regions. Then, we compared gene expression between schizophrenic patients and controls in 4 peripheral tissues.
Results
We observed
C4
overexpression in the DLPFC, parietal, temporal cortex and associative striatum of schizophrenic individuals. We report altered transcriptional patterns of CCP genes in the DLPFC, hippocampus and cerebellum of schizophrenic individuals.
CD46
expression was altered in opposite directions between brain and blood of schizophrenic individuals. No significant alteration of
C4
expression was observed in peripheral tissues.
Conclusions
Our results support the hypothesis of an altered Complement system activity in various brain regions of schizophrenic individuals which may disrupt the synaptic pruning process during adolescence.
Disclosure
No significant relationships.
Abstract Mood spectrum disorders (bipolar disorder, recurrent depressive disorder and seasonal affective disorder) are accompanied by circadian deregulations, which can occur during acute mood ...episodes as well as during euthymic periods, and are particularly common among bipolar patients in remission. This suggests that altered circadian rhythms may be biological markers of these disorders. Rhythm dysfunctions have been observed in mood disorder patients by using actigraphic measures and by assessing social metric rhythms, diurnal preferences and melatonin secretion. Since many of these markers are heritable and therefore driven by clock genes, these genes may represent susceptibility factors for mood spectrum disorders. Indeed, several genetic association studies have suggested that certain circadian gene variants play a role in susceptibility to these disorders. Such connections to circadian genes such as CLOCK, ARNTL1, NPAS2, PER3 and NR1D1 have been repeatedly demonstrated for bipolar disorders, and to a lesser extent for recurrent depressive disorders and seasonal affective disorders. The study of circadian phenotypes and circadian genes in mood spectrum disorders represents a major field of research that may yet reveal the pathophysiological determinants of these disorders.
The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic ...experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France.
The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France.
We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: (1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; (2) age (the elderly form the population most vulnerable to the coronavirus); (3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist/infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic.
French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.
Objective: Duration of untreated illness represents a potentially modifiable component of any diagnosis‐treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically ...defined or not been applied to large clinically representative samples.
Method: In a well‐characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined.
Results: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant‐induced mania).
Conclusion: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD‐II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.
Objective
To provide a systematic review of the literature regarding the efficacy of anti‐inflammatory drugs in three major mental disorders major depressive disorder (MDD), schizophrenia and bipolar ...disorders.
Method
Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open‐labelled clinical and randomized controlled trials (RCTs).
Results
Four major classes of anti‐inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti‐TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta‐analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta‐analysis indicated that COX‐2 specific inhibitors showed effectiveness in schizophrenia. Anti‐TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia.
Conclusion
Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti‐inflammatory drugs are available as adjunct treatment for treatment‐resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side‐effects, they may be reasonable therapeutic alternatives for resistant symptomatology.
The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently ...triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic.
Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms.
The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications.
In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.
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