Loneliness and mood disorders: consequence, cause and/or unholy alliance?

PURPOSE OF REVIEW: People with persistent depressive disorders and with bipolar disorder are more likely to feel lonely than people in the general population. This evidence update focused on studies in the last 2 years, characterized by the COVID-19 pandemic and consequent social distancing directives. RECENT FINDINGS: Longitudinal studies identified that people who feel lonely are more likely to become depressed or to experience relapse of mood disorders. There is emerging evidence that feelings of loneliness or mandatory social isolation can precede manic episodes. Hence the relationship between loneliness and mood disorders is complex and bidirectional. Interventions were developed to reduce loneliness in people with mental health problems, including depressive disorders, through cognitive modification and/or supported socialisation. No loneliness-focused interventions have been specifically tailored to people with bipolar disorder. SUMMARY: Studies carried out before and during the COVID-19 pandemic found that feelings of loneliness can be both consequences and precursors of persistent depression and bipolar disorder. Mood symptoms and loneliness have a cumulative negative effect on physical and mental health outcomes. Conceptual overlaps and relations between loneliness and mood symptoms should be clarified in qualitative studies. Theory-driven intervention models should be developed and tested in methodologically robust studies.

Mood disorders in higher education in Flanders during the 2nd and 3rd COVID-19 wave: Prevalence and help-seeking: Findings from the Flemish College Surveys (FLeCS).

To examine the prevalence of 12-month mood disorders and receipt of mental health treatment among a volunteer sample of higher education students during the 2nd and 3rd COVID-19 wave in the Flanders region. Web-based self-report surveys were obtained from 9101 students in higher education in the Flemish College Surveys (FLeCS) in Flanders, Belgium. As part of the World Health Organization's World Mental Health-International College Student Initiative, we screened for 12-month mood disorders (major depressive episode (MDE), mania/hypomania), and service use. We used poststratification weights to generate population-representative data on key socio-demographic characteristics. 50.6% of the respondents screened positive for 12-month mood disorders (46.8% MDE, of which 22.9% with very severe impact). Use of services was very low, with estimates of 35.4% for MDE, 31.7% for mania, and 25.5% for hypomania. Even among students with very severe disorders, treatment rates were never higher than 48.3%. Most common barriers for not using services were: the preference to handle the problem alone (83.4%) and not knowing where to seek professional help (79.8%). We found a high unmet need for mood problems among college students; though caution is needed in interpreting these findings given the volunteer nature of the sample. A reallocation of treatment resources for higher education students should be considered, particulary services that focus on innovative, low-threshold, and scalable interventions.

Cross-lagged analysis of the relationship between risk perception, physical activity, and adolescent mental health (preprint)

Background Anxiety symptoms were prevalent in teenagers during the new coronavirus pandemic at 31% and depression symptoms were at 34%, both significantly higher than they were before the pandemic, according to research on global adolescent mood disorders during the epidemic. It is unclear, nevertheless, if physical activity still promotes mental health given the perceived danger of sickness, even though it has been demonstrated to be useful in reducing teenage mental health issues. Therefore, this study looked into the relationship between teenage mental health, risk perception, and physical activity. Methods In December 2022 and January 2023, two surveys were given to the same pupils in five high schools. During the New Crown pandemic, the risk perception scores, physical activity levels, and mental health of adolescents were examined in the study N=344. Results For adolescents' risk perceptions, there were significant gender differences (P＜0.01), with gender difference effects of 0.255 (d = 0.416) and 0.195 (d = 0.402) for the two measurements, respectively. For mental health, there were gender differences, with gender difference effects of 0.159 (d = 0.262) and 0.179 (d = 0.278) for the two measurements. The levels of risk perception, physical activity, and teenage mental health met persistent connections across months with contemporaneous correlations, however gender differences in physical activity levels were not significant (p > 0.05); Contrarily, in the cross-lagged study, males had higher levels of physical activity and mental health than females, and teenagers' risk perception was higher. Physical activity and mental health were both predicted by T1 ( values of 0.28, 0.19, and P＜0.01, respectively). Risk perception T1 physical exercise T2 mental health T2 (mediating value impact of 0.012, the Z value of 0.112), as well as the indirect effect of Bootstrap, were all able to predict mental health T2 (β= 0.33, P ＜0.01). Indicating a substantial mediating role for physical activity between risk perception and mental health is the 95% CI, not the 0 value from this pathway. Conclusion Raising awareness of physical activity among adolescents according to gender is important for improving mental health and there is a longitudinal causal relationship between perceived risk of disease, physical activity, and mental health among adolescents, suggesting that physical activity still has a role in mental health in the presence of risk perception.

The Impact of Event Scale – Revised: Examining its cutoff scores among Arab psychiatric patients and healthy adults within the context of COVID-19 as a collective traumatic event (preprint)

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 & 0.91, p values = 0.001, 95% CI: 0.80-0.92 & 0.87 to 0.94, sensitivity = 0.85 & 0.87, specificity = 0.73 & 0.83, Youden index = 0.58 & 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.

Spectrum of Novel Anti-Central Nervous System Autoantibodies in the Cerebrospinal Fluid of 119 Patients With Schizophreniform and Affective Disorders.

BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed. METHODS: Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (n = 30), tissue-based testing was extended to a routine procedure (n = 89). RESULTS: Based on the findings from all 119 patients, anti-CNS immunoglobulin G autoantibodies against brain tissue were detected in 18% (n = 22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p = .026) and white matter changes (p = .020) more frequently than those who tested negative for autoantibodies. CONCLUSIONS: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.

Stress, Genetics and Mood: Impact of COVID-19 on a College Freshman Sample (preprint)

Objectives: Use a longitudinal approach to study the impact of the Covid-19 pandemic on the emergence of symptoms of depression and/or anxiety in college freshmen. Define the interplay between genetic risk and psychosocial factors in shaping vulnerability or resilience to pandemic stress. Methods: University of Michigan freshmen were characterized at baseline using multiple psychological instruments. They were genotyped and polygenic risk score for depression (MDD-PRS) was calculated. Daily physical activity was captured. They were sampled at multiple time points throughout the freshman year on clinical rating scales, including GAD-7 and PHQ-9 for anxiety and depression, respectively. The 2019-2020 cohort (N=122) was compared to an earlier cohort (N=106) to assess the impact of the pandemic. Results: Across cohorts, 25%-57% of freshmen developed significant symptoms of anxiety or depression. In the 2019-2020 cohort, measures of anxiety and depression increased significantly after the onset of COVID-19. Physical activity was dramatically reduced by the pandemic and was associated with the emergence of mood symptoms. Low MDD-PRS subjects exhibited lower relative risk for depression/anxiety during a typical freshman year, but they were more negatively impacted by the pandemic than High MDD-PRS subjects. Conversely, a cluster of psychological indices at baseline predicted resilience in High MDD-PRS subjects who did not develop a mood disorder post-stress. Conclusions: The pandemic had a profound impact on college freshmen triggering depression and anxiety symptoms. Pandemic stress overrode the advantage conferred by "genetic resilience". By contrast, "psychosocial resilience" was protective even in the face of high genetic risk and pandemic stress.

Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders.

Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib (PLX3397) and social isolation. Herein, we adopted PLX3397 to investigate the role of microglia in the modulation of social isolation. Our results found that social isolation during adolescence caused depressive-like, but not anxiety-like behavior in mice in adulthood, with enhanced expression of the microglial marker Iba1 in the hippocampus. In addition, treatment with PLX3397 reduced the expression of the microglial marker Iba1, decreased the mRNA expression of IL-1ß, increased the mRNA expression of Arg1, elevated the protein levels of DCX and GluR1 and restored the dendritic spine branches and density, ultimately mitigating depressive-like behavior in mice. These findings suggest that inhibition of microglia in the hippocampus could ameliorate mood disorders in mice, providing a new perspective for the treatment of psychiatric disorders such as depression.

Measuring Intolerance of Uncertainty after Acquired Brain Injury: Factor Structure, Reliability, and Validity of the Intolerance of Uncertainty Scale-12 (preprint)

Intolerance of uncertainty (IU) is a risk factor for poor mental health. Acquired brain injury (ABI; e.g., stroke, traumatic brain injury), often brings considerable uncertainty and increased mood disorder vulnerability. The Intolerance of Uncertainty Scale-12 (IUS-12) is a brief, well-validated measure of IU argued to comprise two subscales, Prospective Anxiety and Inhibitory Anxiety. Here, for the first time, we investigated its reliability and validity (N = 118), and factor structure (N = 176), in ABI. Both subscales had high test-retest reliability (ICCs of 0.75 and 0.86) and were significantly associated with mood disorder symptoms. The two-factor model was superior to a one-factor IU model fit. IUS-12 scores were stable despite great uncertainties of COVID-19, consistent with its conceptualisation as a trait. Consistent with recent debates about the factor structure of IUS-12 and, in exploratory analyses, we found indications of improved fits that warrant further investigation in independent ABI samples.

The impact of healthcare setting on post-COVID mood disorders: a single-centre perspective from Southern Italy Respiratory Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Post-COVID syndrome includes several clinical identities, with both physical and mental alterations lasting several months from the acute phase of COVID-19 disease. However, to date, data concerning the relationship between healthcare settings during COVID-19 disease and post-COVID mood disorders are lacking. METHODS: We performed a prospective study enrolling 440 patients with post-COVID syndrome. Each patient underwent a complete clinical evaluation, along with blood and functional tests. Patients were divided according to the healthcare setting needed during COVID-19 disease. RESULTS: Patients admitted to RICU were more prone to develop mental alterations, even when compared to ICU-admitted patients. Other risk factors for mood disorders included female gender and some post-COVID symptoms. CONCLUSIONS: Healthcare needs during COVID-19 can explain the higher incidence of mood disorders in post-COVID syndrome. RICU arises as an important but underexplored risk factor for post-COVID psychic sequelae.

Revolving Door Phenomenon and Related Factors in Schizophrenia, Bipolar Affective Disorder and Other Psychotic Disorders.

BACKGROUND: Patients with chronic mental illness are frequently hospitalized and discharged from psychiatry wards. This situation is referred to as the "revolving door phenomenon" (RDP). In addition to factors related to the patient and the disease, limited number of beds leading to shortened hospital stay are among the reasons associated with frequent hospitalization. This study aims to compare patients with RDP and patients with single hospitalization in terms of clinical, sociodemographic, and treatment-oriented characteristics in order to evaluate the risk factors causing frequent hospitalization. SUBJECTS AND METHODS: In this study, patients who were admitted and hospitalized between May 1, 2011 - May 1, 2016 were retrospectively evaluated from patient records. The RDP group consisted of 74 patients and the single-hospitalization group consisted of 59 patients who met inclusion criteria. RESULTS: The RDP group had significantly higher rates of male gender, ECT history, past suicide attempts, multiple drug treatment, clozapine use, legal incidents, and noncompliance to follow up following discharge compared to the single-hospitalization group (p<0.05). CONCLUSION: This study demonstrates that Turkey also has RDP patients with characteristics and hospitalization patterns similar to patients in countries with different cultural, social, and economic conditions. It is important to identify and correct factors that cause frequent hospitalization as it will reduce the burden of the health system as well as provide benefit to the patient.

Views and experiences of Every Mind Matters, Public Health England’s adult mental health literacy campaign: a qualitative interview study (preprint)

Background Every Mind Matters is a publicly funded health campaign, launched in England in 2019, to equip adults to look after their mental health, and that of others, by offering online information about common problems: anxiety, low mood, sleep, stress. This study is one component of an independent evaluation of Every Mind Matters conducted by the NIHR Mental Health Policy Research Unit. Its aim is to explore individuals’ experiences and views of the Every Mind Matters campaign and website. Methods Four researchers, including three with lived experience of using mental health services, conducted 20, one-off, semi-structured, online interviews with a range of adult participants, including a sample of EMM users and a purposively recruited sub-sample known to have severe or long-term mental health conditions. The team took a codebook approach to the analysis of the transcripts and identified four main themes. Findings There was an expectation from the name Every Mind Matters that its advice would address everyone. Almost all participants had experience of mental distress and looked to Every Mind Matters for help with a current problem for themselves. All participants were complimentary about the Every Mind Matters website and found it to be user-friendly (theme 1) and personalised (theme 2) especially the interactive feature ‘Your Mind Plan quiz’ which responds with suggested actions to improve wellbeing and follows up with reminder emails. A few participants found this life changing. Some participants wanted Every Mind Matters to better acknowledge the contexts in which they live (theme 3) such as the limitations of health conditions and health services, and difficulties of crowded housing, social policy, and climate change. Many participants would like Every Mind Matters to do more (theme 4), offer more interactivity, more choice, more information about available treatments, and more stratified advice to cover more severe mental health conditions so that everyone is included. Conclusion The population that experiences common mental health difficulties is not separate from the population that has severe mental health problems. Every Mind Matters could continue and build on its success by addressing a wider range of needs.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

The Place of Care under Constraint for Mood Disorders in the Context of the Collapse of the Supply of Psychiatric Care during the COVID-19 Crisis.

BACKGROUND: In March 2020, the Belgian population was exposed to a confinement situation that it had never experienced before associated with the collapse in access to psychiatric care. Initially, only emergencies and constrained care continued to operate. In these specific circumstances, where both the overall population and the psychiatric population, was exposed to unique stress factors, what was the role of forced psychiatric internments in the treatment of mood disorders? SUBJECTS AND METHODS: We have measured the number of detentions for observation with and without suicide attempt over the two years prior to the pandemic in order to obtain theoretical reference values. We have compared these values with the measures over the 12 months following the start of the confinement period, which constitute the Crisis values. The continuation of measures, with an equal number of observation measures, constituted the Post-Crisis values. For these same cases, we compared in suicide attempt cases, whether the criteria for Severe Major Depressive Disorder were met or not. Lastly we compared the number of observation measures that were lifted, or not, within ten days of patient care. RESULTS: There was no significant increase in Detentions for Observation following a suicide attempt during the Crisis period. However a significant increase was observed during the Post-Crisis period. As regards cases of attempted suicide during the Crisis period, the number of patients suffering from Major Depressive Disorders reduced significantly in terms of statistics. This confirms our impression of a change in population. The Post-Crisis values dropped to the Theoric values. The number of Observation measures lifted increased quite significantly during the Crisis period, while there was a return to values in terms of statistics similar to the Theoric values during the Post-Crisis period. CONCLUSIONS: Although the population, both the healthy population and those suffering from a psychiatric condition, was subject to stress that it had never before experienced coinciding with a collapse of healthcare provision, there was no increase in patients meeting the criteria to benefit from constrained care during the Crisis period. On the other hand, there was a significant change in statistical terms in the population of patients who attempted suicide. We have seen a collapse in the number of patients suffering from depressive disorders and an equivalent increase in the number of patients with personality disorders or adjustment disorders. The number of Observation measures lifted during the Crisis period also grew quite significantly. Constrained care was available to help manage reactive suicide attempts. All other things being equal, they indirectly showed a reduction in Major Depressive Disorders requiring constrained care in the population.

The Listening Experience in a Group of Adolescents with Mood Disorders.

At the Istituto Superiore "Grazio Cossali" secondary school in Orzinuovi (Brescia province) for COVID-19 pandemic emergency, and active listening project through individual and group counselling was proposed. Seven sample classes were selected for which a questionnaire was specifically designed, the students (male and female) were between the ages of 14 and 18. From the results of the questionnaire and the clinical observation, a part of the students show mood disorders with depression type symptoms, attention and concentration difficulties, decrease in academic performance, difficulty in managing emotions, irritability, behavioural fidgeting, displays of anxiety. Furthermore, the individual listening desk was set up to which all the students at the school had access. The primary objective of the project was that of improving emotional, relationship and behavioural issues. Several methodologies were used, such as: participant observation, brainstorming, psychoeducation, active listening, communicative feedback, reactivation of resources. From the active listening carried out in group and individually, the emotional awareness triggered an improvement in the ability to manage emotions in the student, reactivating their own personal resources and improving mood.

Long-term mental health outcomes after SARS-CoV-2 infection: prospective cohort study (preprint)

Background Despite previous evidence from retrospective cohorts suggest that survivors of COVID-19 may be at increased risk of psychiatric sequelae, questions remain on the incidence and absolute risk of psychiatric outcomes, and on the potential protective effect of vaccination. Addressing these knowledge gaps will help public health and clinical service planning during the ongoing pandemic. Methods Based on UK Biobank prospective data, we constructed a SARS-CoV-2 infection cohort including participants with a positive PCR test for SARS-CoV-2 between March 1, 2020 and September 30, 2021; a contemporary control cohort with no evidence of SARS-CoV-2, and a historical control cohort predating the COVID-19 pandemic. Additional control cohorts were constructed for benchmarking, including participants diagnosed with other respiratory tract infection, or with a negative SARS-CoV-2 test. We used propensity score weighting using predefined (clinically informed) and data-driven covariates to minimize confounding. We then estimated incidence rates and risk of first psychiatric disorders diagnosed by ICD-10 codes and psychotropic prescriptions after SARS-CoV-2 infection using cause-specific Cox models. Results In this prospective cohort including 406,579 adults (224,681 women, 181,898 men; mean [SD] age 66.1 [8.4] years), 26,181 had a SARS-CoV-2 infection. Compared with contemporary controls (n=380,398), COVID-19 survivors had increased risks of subsequent psychiatric diagnoses (HR: 2.02, 95% CI 1.85-2.21; difference in incidence rate: 24.85, 95 CI 20.69-29.39 per 1000 person-years) and psychotropic prescriptions (HR: 1.61, 95% CI 1.48-1.75; difference in incidence rate: 21.77, 95% CI 16.59-27.54 per 1000 person-years). Regarding individual mental health related outcomes, the SARS-CoV-2 infection cohort showed an increased risk of psychotic disorders (2.26, 1.28-3.98), mood disorders (2.19, 1.92-2.50), anxiety disorders (2.08, 1.82-2.38), substance use disorders (1.59, 1.34-1.90), sleep disorders (1.95, 1.60-2.39); and prescriptions for antipsychotics (3.78, 2.74-5.21), antidepressants (1.55, 1.29-1.87), benzodiazepines (1.82, 1.58-2.11), and opioids (1.40, 1.26-1.55). Overall, the risk of any mental health outcome was increased with a HR of 1.58, 95% CI 1.47-1.70; and difference in incidence rate of 32.04, 25.76-38.81 per 1000 person-years. These results were consistent when comparing to a historical control cohort. Additionally, mental health risks were increased even further in participants who tested positive in hospital settings. Finally, participants who were fully vaccinated had a lower risk of mental health outcomes compared to those infected when unvaccinated or partially vaccinated. All observed risks of mental health outcomes were attenuated or even lower after SARS-CoV-2 infection compared with those with other respiratory infections, or with participants in the test-negative control cohort. Conclusions In this prospective cohort study, people who survived COVID-19 were at increased risk of psychiatric outcomes and related psychotropic medications. These risks were higher in those with more severe disease, treated in hospital settings, and were significantly reduced in fully vaccinated people. Of note, compared to participants with other respiratory infections or with only negative testing results, those infected with SARS-CoV-2 had an even lower risk of mental health outcomes, warranting further research into causation. The early identification and treatment of psychiatric disorders among survivors of COVID-19 should be a priority in the long-term management of COVID-19. Particular attention might be needed for those with severe (hospitalized) disease and those who were not fully vaccinated at the time of infection.

Increase in prevalence of current mental disorders in the context of COVID-19: analysis of repeated nationwide cross-sectional surveys.

AIMS: The United Nations warned of COVID-19-related mental health crisis; however, it is unknown whether there is an increase in the prevalence of mental disorders as existing studies lack a reliable baseline analysis or they did not use a diagnostic measure. We aimed to analyse trends in the prevalence of mental disorders prior to and during the COVID-19 pandemic. METHODS: We analysed data from repeated cross-sectional surveys on a representative sample of non-institutionalised Czech adults (18+ years) from both November 2017 (n = 3306; 54% females) and May 2020 (n = 3021; 52% females). We used Mini International Neuropsychiatric Interview (MINI) as the main screening instrument. We calculated descriptive statistics and compared the prevalence of current mood and anxiety disorders, suicide risk and alcohol-related disorders at baseline and right after the first peak of COVID-19 when related lockdown was still in place in CZ. In addition, using logistic regression, we assessed the association between COVID-19-related worries and the presence of mental disorders. RESULTS: The prevalence of those experiencing symptoms of at least one current mental disorder rose from a baseline of 20.02 (95% CI = 18.64; 21.39) in 2017 to 29.63 (95% CI = 27.9; 31.37) in 2020 during the COVID-19 pandemic. The prevalence of both major depressive disorder (3.96, 95% CI = 3.28; 4.62 v. 11.77, 95% CI = 10.56; 12.99); and suicide risk (3.88, 95% CI = 3.21; 4.52 v. 11.88, 95% CI = 10.64; 13.07) tripled and current anxiety disorders almost doubled (7.79, 95% CI = 6.87; 8.7 v. 12.84, 95% CI = 11.6; 14.05). The prevalence of alcohol use disorders in 2020 was approximately the same as in 2017 (10.84, 95% CI = 9.78; 11.89 v. 9.88, 95% CI = 8.74; 10.98); however, there was a significant increase in weekly binge drinking behaviours (4.07% v. 6.39%). Strong worries about both, health or economic consequences of COVID-19, were associated with an increased odds of having a mental disorder (1.63, 95% CI = 1.4; 1.89 and 1.42, 95% CI = 1.23; 1.63 respectively). CONCLUSIONS: This study provides evidence matching concerns that COVID-19-related mental health problems pose a major threat to populations, particularly considering the barriers in service provision posed during lockdown. This finding emphasises an urgent need to scale up mental health promotion and prevention globally.

Manifestations Associated with Post Acute Sequelae of SARS-CoV2 Infection (PASC) Predict Diagnosis of New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies (preprint)

Acute COVID-19 infection can be followed by persistent or newly diagnosed manifestations in many different organ systems, referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Numerous studies have shown an increased risk of being diagnosed with new-onset psychiatric disease in the first 21-120 days following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of receiving a diagnosis of new-onset psychiatric disease following COVID-19. Here, we perform a retrospective electronic health record (EHR) cohort study to evaluate whether non-psychiatric PASC-AMs can predict whether patients will receive a diagnosis of new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 65 clinical organizations which are harmonized using the Observational Medical Outcomes Partnership (OMOP) data model. Non-psychiatric PASC-AMs were recorded 21-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. OMOP codes were mapped to 178 Human Phenotype Ontology (HPO) terms that represent PASC-AMs. Logistic regression was applied to predict newly diagnosed psychiatric disease occurrence based on age, sex, race, pre-existing comorbidities, and PASC-AMs in eleven categories. The cohort of 1,135,973 individuals with acute COVID-19 had a mean age of 40.5 years and included 56.0% females. We found a significant association for seven of the HPO categories with newly diagnosed psychiatric disease, with odds ratios highest for neurological (2.30, 2.24-2.36) and cardiovascular (1.77, 1.69-1.85) PASC-AMs. Secondary analysis revealed that the proportions of 95 of 154 individual phenotypic features differed significantly among patients diagnosed with different psychiatric diseases (anxiety, mood disorders, dementia, and psychosis). Neurological, pulmonary, gastrointestinal, endocrine, cardiovascular, constitutional, and ENT PASC-AMs are each associated with an increased risk of newly diagnosed psychiatric disease. This suggests that the total burden of PASC-AMs influences the risk of receiving a diagnosis of a new-onset psychiatric disease. This finding may be used to inform psychiatric screening following acute COVID-19 by identifying high-risk patients.