[Combination of ketamine and esketamine with Exposure and Response Prevention (ERP) therapy for Obsessive-Compulsive Disorder]. / Combinaison de la kétamine et de l'eskétamine avec la thérapie d'exposition avec prévention de la réponse (EPR) dans le trouble obsessionnel-compulsif.

Obsessive-Compulsive Disorder (OCD), characterized by the combination of obsession and compulsion, is a clinical and therapeutic challenge. Many patients with OCD do not respond to first-line treatments such as serotonin selective reuptake inhibitors (SSRIs) and exposure and response prevention psychotherapy (ERP). For these resistant patients, some preliminary studies have shown that ketamine, a non-selective glutamatergic NMDA receptors antagonist, could improve the obsessive symptoms. A number of these studies have also suggested that the combination of ketamine with ERP psychotherapy may jointly potentiate the effectiveness of ketamine and ERP. In this paper, we present the existing data on the combined use of ketamine with ERP psychotherapy for OCD. We suggest that modulation of NMDA receptor activity and glutamatergic signaling by ketamine may promote the therapeutic mechanisms involved in ERP such as fear extinction and brain plasticity mechanisms. Finally, we propose a ketamine-augmented ERP psychotherapy (KAP-ERP) protocol in OCD, and we present the limitations associated with its application in clinical practice.

SARS-CoV-2 Psychiatric Sequelae: An Urgent Need of Prevention.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for COVID-19 pandemic, caused catastrophic health and social effects, but little is known about its consequences on mental health. Other viral infections have been associated with psychiatric sequelae: infection-triggered disturbing of the immune system and the stressful intensive unit care can cause psychological and psychiatric complications. Moreover, SARS-CoV-2 can potentially induce neuronal injuries, leading to neurocognitive disabilities. Previous studies during the COVID-19 pandemic reported a high occurrence rate of psychopathological and neurocognitive conditions among COVID-19 survivors, highlighting the need for screening for these impairments in order to implement early interventions and secondary prevention. However, many psychiatric disorders can take several years to develop, and it is still difficult to differentiate between factors linked to the infection itself or to the global context of the pandemic. In this review, we describe the effects of SARS-CoV-2 infection on mental health, the mechanisms involved in psychiatric and neurocognitive sequelae, and the strategies of prevention and management. More studies are needed to investigate the effects of a range of factors including clinical, sociodemographic, and inflammatory predictors. These efforts could be useful to identify high-risk individuals and inform targeted preventive actions.

Cell-Fusing Agent Virus Reduces Arbovirus Dissemination in Aedes aegypti Mosquitoes In Vivo.

Aedes aegypti mosquitoes are the main vectors of arthropod-borne viruses (arboviruses) of public health significance, such as the flaviviruses dengue virus (DENV) and Zika virus (ZIKV). Mosquitoes are also the natural hosts of a wide range of viruses that are insect specific, raising the question of their influence on arbovirus transmission in nature. Cell-fusing agent virus (CFAV) was the first described insect-specific flavivirus, initially discovered in an A. aegypti cell line and subsequently detected in natural A. aegypti populations. It was recently shown that DENV and the CFAV strain isolated from the A. aegypti cell line have mutually beneficial interactions in mosquito cells in culture. However, whether natural strains of CFAV and DENV interact in live mosquitoes is unknown. Using a wild-type CFAV isolate recently derived from Thai A. aegypti mosquitoes, we found that CFAV negatively interferes with both DENV type 1 and ZIKV in vitro and in vivo For both arboviruses, prior infection by CFAV reduced the dissemination titer in mosquito head tissues. Our results indicate that the interactions observed between arboviruses and the CFAV strain derived from the cell line might not be a relevant model of the viral interference that we observed in vivo Overall, our study supports the hypothesis that insect-specific flaviviruses may contribute to reduce the transmission of human-pathogenic flaviviruses.IMPORTANCE The mosquito Aedes aegypti carries several arthropod-borne viruses (arboviruses) that are pathogenic to humans, including dengue and Zika viruses. Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. Although interactions between cell-fusing agent virus and dengue virus have been documented in mosquito cells in culture, whether wild strains of cell-fusing agent virus interfere with arbovirus transmission by live mosquitoes was unknown. We used an experimental approach to demonstrate that cell-fusing agent virus infection reduces the propagation of dengue and Zika viruses in A. aegypti mosquitoes. These results support the idea that insect-only viruses in nature can modulate the ability of mosquitoes to carry arboviruses of medical significance and that they could possibly be manipulated to reduce arbovirus transmission.