key: cord-0969791-i6d858ko
authors: Gil, E. Martín; Martínez-Suero, L.; Revuelta, J. Rodríguez; Suárez, L. Pérez; Martínez-Cao, C.; Fernández, A. García; Moya-Lacasa, C.; González-Blanco, L.; Saiz, P.A.; García-Portilla, M.P.; Bobes, J.
title: P.0647 Psychological impact in patients with common mental disorders after six months of COVID-19 outbreak
date: 2021-12-30
journal: Eur Neuropsychopharmacol
DOI: 10.1016/j.euroneuro.2021.10.611
sha: 39cda85c6abbbbfd3ad3051cfd75aa53567cb9a7
doc_id: 969791
cord_uid: i6d858ko

Introduction: Studies focused on the impact of the COVID-19 pandemic in patients with psychiatric disorders have reported a deterioration of their mental health due to this situation [1]. A study focused on the early COVID-19 pandemic consequences on mental health found that participants reporting a current mental disorder were experiencing the greatest psychological impact, followed by those reporting a past mental disorder [2]. We hypothesize that having suffered or suffering from a depressive or anxiety disorder at that time can lead to maladaptive responses during the pandemic and social restrictions. Aims of the study: To describe the psychological impact among patients with a current or past diagnosis of Common Mental Disorders (CMD;anxiety and depressive disorders) after six months of the beginning of the COVID-19 pandemic. 1. To explore risk and protective factors associated with a Severe Psychological Impact (SPI). Methods: Cross-sectional survey. A self-reported online test was completed by the participants during the pandemic from October 14th to November 8th, 2020, from all over the Spanish territory. From the sample (N=5900), 1122 (19.02%) reported suffering from CMD in the past or at the moment the study was conducted (mean age±SD=46.01 ±14.12 years) The Spanish version of the Depression, Anxiety and Stress Scale (DASS-21) was used to evaluate the maladaptive psychological responses. Psychological impact in CMD was classified according to the number of maladaptive responses in the DASS-21 scale, considering: mild (1 response), moderate (2 responses) and severe (3 responses). Statistical analyses: Chi-square, t-student test (IBM SPSS version 24 was used for data analyses). The p-value was set at <0.05. Results: Women represented 70.1% of the sample. Approximately half of the participants were married or were living with a cohabiting partner (55.8%). Most of the responders had completed university studies (69.6%). From the sample, 1240 participants (21%) had a somatic disease (12% hypertension and 10.8% chronic respiratory disease). 16.1% increased their alcohol consumption and 14.1% increased their tobacco consumption. CMD reported the highest psychological impact on Depressive DASS-21 subscale (59.5% χ²=206.6, p<0.001), followed by Stress subscale (38.6, χ²= 482.2, p<0.001) and Anxiety subscale (31.3, χ²= 204.7, p<0.001). According to copying strategies, a high percentage of patients with CMD reported being able to enjoy leisure time (88.1%). Reading or listening to music were the most frequent activities (87.8%). 20.7% of the sample showed a SPI. Considering the statistically significant variables, a logistic regression analysis was obtained. On the one hand, older age (B=-0.03, OR=0.972, p<0.001), male sex (B=-0.6, OR=0.55, p=0.008), university studies (B=-0.43, OR=0.652, p=0.008) and being able to enjoy leisure time (B=-1.1, OR=0.341, p<0.001) were protective factors of SPI. On the other hand, having a somatic illness (B=0.59, OR=1.797, p<0.001) and the increase in tobacco use (B=0.58, OR=1.778, p=0.005) were factors associated with SPI. Conclusions: This study illustrates the psychological impact in CMD after half-year of the COVID-19 outbreak. Being young, a woman, suffering from somatic illness, and not having a university education are risk factors for SPI. However, being able to enjoy leisure time is the main protective factor against a SPI in CMD. No conflict of interest

reason, it might could be useful to propose screening tools to all pregnant women and during their first year of postpartum, in order to early identify and provide preventive and therapeutic strategies to help this particularly vulnerable population.

References [1] Introduction: Studies focused on the impact of the COVID-19 pandemic in patients with psychiatric disorders have reported a deterioration of their mental health due to this situation [1] . A study focused on the early COVID-19 pandemic consequences on mental health found that participants reporting a current mental disorder were experiencing the greatest psychological impact, followed by those reporting a past mental disorder [2] . We hypothesize that having suffered or suffering from a depressive or anxiety disorder at that time can lead to maladaptive responses during the pandemic and social restrictions. Aims of the study: To describe the psychological impact among patients with a current or past diagnosis of Common Mental Disorders (CMD; anxiety and depressive disorders) after six months of the beginning of the COVID-19 pandemic.

1. To explore risk and protective factors associated with a Severe Psychological Impact (SPI The neuropeptide oxytocin (OXT) regulates multiple social and emotional behaviors, such as social bonding, reciprocal trust, aggression, fear and anxiety, both in animals and humans. A non-synonymous single nucleotide polymorphism (SNP) in the OXT receptor (OXTR) gene rs4686302, resulting in the OXTR variant A218T, has been associated with core characteristics of autism spectrum disorder, social cognition deficits and attention disorders, and with trait empathy in healthy persons. However, the underlying molecular and intracellular mechanisms are unknown. In this study, we aimed to reveal functional consequences of expression of the OXTR variant A218T at cellular level. Methods: In this functional in vitro study we created two monoclonal HEK293 cell lines, stably expressing either the OXTR wildtype or the A218T variant in order to assess the molecular and cellular consequences of expression of the OXTR variant. HEK293 cells were transduced with an N-terminal FLAG-tagged OXTR comprising either the wildtype or the rs4686302 SNP sequence. Single clones of OXTR-positive cells were isolated using FACS to create both WT and SNP-containing monoclonal cell lines. Protein stability and/or turnover of the wildtype and SNP OXTR were compared using cycloheximide degradation assay. As OXTR activation results in Ca 2 + release from intracellular stores as well as Ca 2 + influx from the extracellular space, we monitored stimulated intracellular Ca 2 + levels in both cell lines using calcium fluorescence imaging. To assess SNP-associated alterations in OXTR-mediated intracellular signaling, we studied activation of the MAPK pathway downstream of the OXTR, with ERK1/2 being the essential core factor for the anxiolytic and anti-stress effects of OXT using Western-blot. As both OXTR-activated pathways signal to the nucleus to regulate gene transcription, we also performed RNA sequencing in WT and SNP-containing cells to identify differentially regulated genes. Finally, we performed molecular and systems biology modeling in an attempt to validate our in vitro results. Results: We can provide a mechanistic explanation for an altered receptor function and revealed that the expression of the OXTR variant A218T results in an increased OXTR protein stability and in altered OXT-induced intracellular signaling. Specifically, we detected a shift in Ca 2 + dynamics and reduced MAPK pathway activation in OXT-treated A218T cells. Combined whole genome and RNA sequencing analyses in OXT-treated cells revealed 7823 differentially regulated genes in A218T compared to wildtype cells, including 429 genes being associated with autism spectrum disorder. Furthermore, computational modeling provided a molecular basis for the observed change in OXTR stability. Conclusions: Our results based on the combination of in vitro and in silico approaches used in this work provide new insights into the cellular effects of genetic variations affecting the OXTR and their functional consequences on cellular processes as well as gene expression. Thus, our study opens the way for future rational drug design efforts. Supported by Deutsche Forschungs-Gemeinschaft (DFG) (BJ, IDN). 

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