Top 20 cited since 2017


Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA

Taquet, M., Luciano, S., Geddes, J.R., Harrison, P.J. 2021 The Lancet Psychiatry

8(2), pp. 130-140


Background: Adverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors. In this electronic health record network cohort study using data from 69 million individuals, 62 354 of whom had a diagnosis of COVID-19, we assessed whether a diagnosis of COVID-19 (compared with other health events) was associated with increased rates of subsequent psychiatric diagnoses, and whether patients with a history of psychiatric illness are at a higher risk of being diagnosed with COVID-19. Methods: We used the TriNetX Analytics Network, a global federated network that captures anonymised data from electronic health records in 54 health-care organisations in the USA, totalling 69·8 million patients. TriNetX included 62 354 patients diagnosed with COVID-19 between Jan 20, and Aug 1, 2020. We created cohorts of patients who had been diagnosed with COVID-19 or a range of other health events. We used propensity score matching to control for confounding by risk factors for COVID-19 and for severity of illness. We measured the incidence of and hazard ratios (HRs) for psychiatric disorders, dementia, and insomnia, during the first 14 to 90 days after a diagnosis of COVID-19. Findings: In patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events (HR 2·1, 95% CI 1·8–2·5 vs influenza; 1·7, 1·5–1·9 vs other respiratory tract infections; 1·6, 1·4–1·9 vs skin infection; 1·6, 1·3–1·9 vs cholelithiasis; 2·2, 1·9–2·6 vs urolithiasis, and 2·1, 1·9–2·5 vs fracture of a large bone; all p<0·0001). The HR was greatest for anxiety disorders, insomnia, and dementia. We observed similar findings, although with smaller HRs, when relapses and new diagnoses were measured. The incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18·1% (95% CI 17·6–18·6), including 5·8% (5·2–6·4) that were a first diagnosis. The incidence of a first diagnosis of dementia in the 14 to 90 days after COVID-19 diagnosis was 1·6% (95% CI 1·2–2·1) in people older than 65 years. A psychiatric diagnosis in the previous year was associated with a higher incidence of COVID-19 diagnosis (relative risk 1·65, 95% CI 1·59–1·71; p<0·0001). This risk was independent of known physical health risk factors for COVID-19, but we cannot exclude possible residual confounding by socioeconomic factors. Interpretation: Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae, and a psychiatric diagnosis might be an independent risk factor for COVID-19. Although preliminary, our findings have implications for clinical services, and prospective cohort studies are warranted. Funding: National Institute for Health Research.


6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Taquet, M., Geddes, J.R., Husain, M., Luciano, S., Harrison, P.J. 2021 The Lancet Psychiatry

8(5), pp. 416-427


Background: Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. Methods: For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. Findings: Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. Interpretation: Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. Funding: National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.


Trajectories of anxiety and depressive symptoms during enforced isolation due to COVID-19 in England: a longitudinal observational study

Fancourt, D., Steptoe, A., Bu, F. 2021 The Lancet Psychiatry

8(2), pp. 141-149


Background: There is major concern about the impact of the global COVID-19 outbreak on mental health. Several studies suggest that mental health deteriorated in many countries before and during enforced isolation (ie, lockdown), but it remains unknown how mental health has changed week by week over the course of the COVID-19 pandemic. This study aimed to explore the trajectories of anxiety and depression over the 20 weeks after lockdown was announced in England, and compare the growth trajectories by individual characteristics. Methods: In this prospective longitudinal observational study, we analysed data from the UCL COVID-19 Social Study, a panel study weighted to population proportions, which collects information on anxiety (using the Generalised Anxiety Disorder assessment) and depressive symptoms (using the Patient Health Questionnaire) weekly in the UK since March 21, 2020. We included data from adults living in England who had at least three repeated measures between March 23 and Aug 9, 2020. Analyses were done using latent growth models, which were fitted to account for sociodemographic and health covariates. Findings: Between March 23, and Aug 9, data from over 70 000 adults were collected in the UCL COVID-19 Social Study. When including participants living in England with three follow-up measures and no missing values, our analytic sample consisted of 36 520 participants. The average depression score was 6·6 (SD=6·0, range 0–27) and the average anxiety score 5·7 (SD=5·6, range 0–21) in week 1. Anxiety and depression levels both declined across the first 20 weeks following the introduction of lockdown in England (b=–1·93, SE=0·26, p<0·0001 for anxiety; b=–2·52, SE=0·28, p<0·0001 for depressive symptoms). The fastest decreases were seen across the strict lockdown period (between weeks 2 and 5), with symptoms plateauing as further lockdown easing measures were introduced (between weeks 16 and 20). Being a woman or younger, having lower educational attainment, lower income, or pre-existing mental health conditions, and living alone or with children were all risk factors for higher levels of anxiety and depression at the start of lockdown. Many of these inequalities in experiences were reduced as lockdown continued, but differences were still evident 20 weeks after the start of lockdown. Interpretation: These data suggest that the highest levels of depression and anxiety occurred in the early stages of lockdown but declined fairly rapidly, possibly because individuals adapted to circumstances. Our findings emphasise the importance of supporting individuals in the lead-up to future lockdowns to try to reduce distress, and highlight that groups already at risk for poor mental health before the pandemic have remained at risk throughout lockdown and its aftermath. Funding: Nuffield Foundation, UK Research and Innovation, Wellcome Trust.


Prevalence of symptoms of depression, anxiety, insomnia, posttraumatic stress disorder, and psychological distress among populations affected by the COVID-19 pandemic: A systematic review and meta-analysis

Cénat, J.M., Blais-Rochette, C., Kokou-Kpolou, C.K., (...), Goulet, M.-A., Labelle, R.P. 2021 Psychiatry Research



Objective: We conducted a systematic review and meta-analysis to estimate the pooled prevalence of depression, anxiety, insomnia, PTSD, and Psychological distress (PD) related to COVID-19 among affected populations. Methods: We searched articles in Medline, Embase, APA PsycInfo, CINAHL, Scopus, and Web of Science. Random-effects meta-analyses on the proportions of individuals with symptoms of depression, anxiety, insomnia, PTSD, and PD were generated and between-group differences for gender, healthcare workers (HCWs), and regions where studies were conducted. Results: A total of 2189 articles were screened, 136 full-text articles were assessed for eligibility. Fifty-five peer-reviewed studies met inclusion criteria for the meta-analysis (N=189,159). The prevalence of depression (k=46) was 15.97% (95%CI, 13.24-19.13). The prevalence of anxiety (k=54) was 15.15% (95%CI, 12.29-18.54). The prevalence of insomnia (k=14) was 23.87% (95%CI, 15.74-34.48). The prevalence of PTSD (k=13) was 21.94% (95%CI, 9.37-43.31). Finally, the prevalence of psychological distress (k=19) was 13.29% (95%CI, 8.80-19.57). Between-group differences were only found in HCWs (z=2.69, p < 0.05) who had a higher prevalence of insomnia than others. Conclusions: Findings suggest that the short-term mental health consequences of COVID-19 are equally high across affected countries, and across gender. However, reports of insomnia are significantly higher among HCWs than the general population.


The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts

Pan, K.-Y., Kok, A.A.L., Eikelenboom, M., (...), Giltay, E.J., Penninx, B.W.J.H. 2021 The Lancet Psychiatry

8(2), pp. 121-129


Background: The impact of the COVID-19 pandemic on mental health in people with pre-existing mental health disorders is unclear. In three psychiatry case-control cohorts, we compared the perceived mental health impact and coping and changes in depressive symptoms, anxiety, worry, and loneliness before and during the COVID-19 pandemic between people with and without lifetime depressive, anxiety, or obsessive-compulsive disorders. Methods: Between April 1 and May 13, 2020, online questionnaires were distributed among the Netherlands Study of Depression and Anxiety, Netherlands Study of Depression in Older Persons, and Netherlands Obsessive Compulsive Disorder Association cohorts, including people with (n=1181) and without (n=336) depressive, anxiety, or obsessive-compulsive disorders. The questionnaire contained questions on perceived mental health impact, fear of COVID-19, coping, and four validated scales assessing depressive symptoms, anxiety, worry, and loneliness used in previous waves during 2006–16. Number and chronicity of disorders were based on diagnoses in previous waves. Linear regression and mixed models were done. Findings: The number and chronicity of disorders showed a positive graded dose–response relation, with greater perceived impact on mental health, fear, and poorer coping. Although people with depressive, anxiety, or obsessive-compulsive disorders scored higher on all four symptom scales than did individuals without these mental health disorders, both before and during the COVID-19 pandemic, they did not report a greater increase in symptoms during the pandemic. In fact, people without depressive, anxiety, or obsessive-compulsive disorders showed a greater increase in symptoms during the COVID-19 pandemic, whereas individuals with the greatest burden on their mental health tended to show a slight symptom decrease. Interpretation: People with depressive, anxiety, or obsessive-compulsive disorders are experiencing a detrimental impact on their mental health from the COVID-19 pandemic, which requires close monitoring in clinical practice. Yet, the COVID-19 pandemic does not seem to have further increased symptom severity compared with their prepandemic levels. Funding: Dutch Research Council.


COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States

Wang, Q.Q., Kaelber, D.C., Xu, R., Volkow, N.D. 2021 Molecular Psychiatry

26(1), pp. 30-39


The global pandemic of COVID-19 is colliding with the epidemic of opioid use disorders (OUD) and other substance use disorders (SUD) in the United States (US). Currently, there is limited data on risks, disparity, and outcomes for COVID-19 in individuals suffering from SUD. This is a retrospective case-control study of electronic health records (EHRs) data of 73,099,850 unique patients, of whom 12,030 had a diagnosis of COVID-19. Patients with a recent diagnosis of SUD (within past year) were at significantly increased risk for COVID-19 (adjusted odds ratio or AOR = 8.699 [8.411–8.997], P < 10−30), an effect that was strongest for individuals with OUD (AOR = 10.244 [9.107–11.524], P < 10−30), followed by individuals with tobacco use disorder (TUD) (AOR = 8.222 ([7.925–8.530], P < 10−30). Compared to patients without SUD, patients with SUD had significantly higher prevalence of chronic kidney, liver, lung diseases, cardiovascular diseases, type 2 diabetes, obesity and cancer. Among patients with recent diagnosis of SUD, African Americans had significantly higher risk of COVID-19 than Caucasians (AOR = 2.173 [2.01–2.349], P < 10−30), with strongest effect for OUD (AOR = 4.162 [3.13–5.533], P < 10−25). COVID-19 patients with SUD had significantly worse outcomes (death: 9.6%, hospitalization: 41.0%) than general COVID-19 patients (death: 6.6%, hospitalization: 30.1%) and African Americans with COVID-19 and SUD had worse outcomes (death: 13.0%, hospitalization: 50.7%) than Caucasians (death: 8.6%, hospitalization: 35.2%). These findings identify individuals with SUD, especially individuals with OUD and African Americans, as having increased risk for COVID-19 and its adverse outcomes, highlighting the need to screen and treat individuals with SUD as part of the strategy to control the pandemic while ensuring no disparities in access to healthcare support.


Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries

Pirkis, J., John, A., Shin, S., (...), Gunnell, D., Spittal, M.J. 2021 The Lancet Psychiatry

8(7), pp. 579-588


Background: The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world. Methods: We sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries’ ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms “suicide” and “cause of death”, before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis). Findings: We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales, Australia (RR 0·81 [95% CI 0·72–0·91]); Alberta, Canada (0·80 [0·68–0·93]); British Columbia, Canada (0·76 [0·66–0·87]); Chile (0·85 [0·78–0·94]); Leipzig, Germany (0·49 [0·32–0·74]); Japan (0·94 [0·91–0·96]); New Zealand (0·79 [0·68–0·91]); South Korea (0·94 [0·92–0·97]); California, USA (0·90 [0·85–0·95]); Illinois (Cook County), USA (0·79 [0·67–0·93]); Texas (four counties), USA (0·82 [0·68–0·98]); and Ecuador (0·74 [0·67–0·82]). Interpretation: This is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic effects of the pandemic unfold. Funding: None.


Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

Davis, A.K., Barrett, F.S., May, D.G., (...), Finan, P.H., Griffiths, R.R. 2021 JAMA Psychiatry

78(5), pp. 481-489


Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective: To investigate the effect of psilocybin therapy in patients with MDD. Design, Setting, and Participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main Outcomes and Measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P <.001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P <.001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P <.001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P <.001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Conclusions and Relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial Registration: Identifier: NCT03181529.


Trends in US Emergency Department Visits for Mental Health, Overdose, and Violence Outcomes before and during the COVID-19 Pandemic

Holland, K.M., Jones, C., Vivolo-Kantor, A.M., (...), Dowling, N.F., Houry, D. 2021 JAMA Psychiatry

78(4), pp. 372-379


Importance: The coronavirus disease 2019 (COVID-19) pandemic, associated mitigation measures, and social and economic impacts may affect mental health, suicidal behavior, substance use, and violence. Objective: To examine changes in US emergency department (ED) visits for mental health conditions (MHCs), suicide attempts (SAs), overdose (OD), and violence outcomes during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study used data from the Centers for Disease Control and Prevention's National Syndromic Surveillance Program to examine national changes in ED visits for MHCs, SAs, ODs, and violence from December 30, 2018, to October 10, 2020 (before and during the COVID-19 pandemic). The National Syndromic Surveillance Program captures approximately 70% of US ED visits from more than 3500 EDs that cover 48 states and Washington, DC. Main Outcomes and Measures: Outcome measures were MHCs, SAs, all drug ODs, opioid ODs, intimate partner violence (IPV), and suspected child abuse and neglect (SCAN) ED visit counts and rates. Weekly ED visit counts and rates were computed overall and stratified by sex. Results: From December 30, 2018, to October 10, 2020, a total of 187508065 total ED visits (53.6% female and 46.1% male) were captured; 6018318 included at least 1 study outcome (visits not mutually exclusive). Total ED visit volume decreased after COVID-19 mitigation measures were implemented in the US beginning on March 16, 2020. Weekly ED visit counts for all 6 outcomes decreased between March 8 and 28, 2020 (March 8: MHCs = 42903, SAs = 5212, all ODs = 14543, opioid ODs = 4752, IPV = 444, and SCAN = 1090; March 28: MHCs = 17574, SAs = 4241, all ODs = 12399, opioid ODs = 4306, IPV = 347, and SCAN = 487). Conversely, ED visit rates increased beginning the week of March 22 to 28, 2020. When the median ED visit counts between March 15 and October 10, 2020, were compared with the same period in 2019, the 2020 counts were significantly higher for SAs (n = 4940 vs 4656, P =.02), all ODs (n = 15604 vs 13371, P <001), and opioid ODs (n = 5502 vs 4168, P <001); counts were significantly lower for IPV ED visits (n = 442 vs 484, P <001) and SCAN ED visits (n = 884 vs 1038, P <001). Median rates during the same period were significantly higher in 2020 compared with 2019 for all outcomes except IPV. Conclusions and Relevance: These findings suggest that ED care seeking shifts during a pandemic, underscoring the need to integrate mental health, substance use, and violence screening and prevention services into response activities during public health crises.


Association of Psychiatric Disorders with Mortality among Patients with COVID-19

Nemani, K., Li, C., Olfson, M., (...), Petkova, E., Goff, D.C. 2021 JAMA Psychiatry

78(4), pp. 380-386


Importance: To date, the association of psychiatric diagnoses with mortality in patients infected with coronavirus disease 2019 (COVID-19) has not been evaluated. Objective: To assess whether a diagnosis of a schizophrenia spectrum disorder, mood disorder, or anxiety disorder is associated with mortality in patients with COVID-19. Design, Setting, and Participants: This retrospective cohort study assessed 7348 consecutive adult patients for 45 days following laboratory-confirmed COVID-19 between March 3 and May 31, 2020, in a large academic medical system in New York. The final date of follow-up was July 15, 2020. Patients without available medical records before testing were excluded. Exposures: Patients were categorized based on the following International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnoses before their testing date: (1) schizophrenia spectrum disorders, (2) mood disorders, and (3) anxiety disorders. Patients with these diagnoses were compared with a reference group without psychiatric disorders. Main Outcomes and Measures: Mortality, defined as death or discharge to hospice within 45 days following a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result. Results: Of the 26540 patients tested, 7348 tested positive for SARS-CoV-2 (mean [SD] age, 54 [18.6] years; 3891 [53.0%] women). Of eligible patients with positive test results, 75 patients (1.0%) had a history of a schizophrenia spectrum illness, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder. After adjusting for demographic and medical risk factors, a premorbid diagnosis of a schizophrenia spectrum disorder was significantly associated with mortality (odds ratio [OR], 2.67; 95% CI, 1.48-4.80). Diagnoses of mood disorders (OR, 1.14; 95% CI, 0.87-1.49) and anxiety disorders (OR, 0.96; 95% CI, 0.65-1.41) were not associated with mortality after adjustment. In comparison with other risk factors, a diagnosis of schizophrenia ranked behind only age in strength of an association with mortality. Conclusions and Relevance: In this cohort study of adults with SARS-CoV-2-positive test results in a large New York medical system, adults with a schizophrenia spectrum disorder diagnosis were associated with an increased risk for mortality, but those with mood and anxiety disorders were not associated with a risk of mortality. These results suggest that schizophrenia spectrum disorders may be a risk factor for mortality in patients with COVID-19.


COVID-19 mental health impact and responses in low-income and middle-income countries: reimagining global mental health

Kola, L., Kohrt, B.A., Hanlon, C., (...), Thornicroft, G., Patel, V. 2021 The Lancet Psychiatry

8(6), pp. 535-550


Most of the global population live in low-income and middle-income countries (LMICs), which have historically received a small fraction of global resources for mental health. The COVID-19 pandemic has spread rapidly in many of these countries. This Review examines the mental health implications of the COVID-19 pandemic in LMICs in four parts. First, we review the emerging literature on the impact of the pandemic on mental health, which shows high rates of psychological distress and early warning signs of an increase in mental health disorders. Second, we assess the responses in different countries, noting the swift and diverse responses to address mental health in some countries, particularly through the development of national COVID-19 response plans for mental health services, implementation of WHO guidance, and deployment of digital platforms, signifying a welcome recognition of the salience of mental health. Third, we consider the opportunity that the pandemic presents to reimagine global mental health, especially through shifting the balance of power from high-income countries to LMICs and from narrow biomedical approaches to community-oriented psychosocial perspectives, in setting priorities for interventions and research. Finally, we present a vision for the concept of building back better the mental health systems in LMICs with a focus on key strategies; notably, fully integrating mental health in plans for universal health coverage, enhancing access to psychosocial interventions through task sharing, leveraging digital technologies for various mental health tasks, eliminating coercion in mental health care, and addressing the needs of neglected populations, such as children and people with substance use disorders. Our recommendations are relevant for the mental health of populations and functioning of health systems in not only LMICs but also high-income countries impacted by the COVID-19 pandemic, with wide disparities in quality of and access to mental health care.


Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study

Hoertel, N., Sánchez-Rico, M., Vernet, R., (...), Burgun, A., Limosin, F. 2021 Molecular Psychiatry

26(9), pp. 5199-5212


A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43–0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.


Increased mood disorder symptoms, perceived stress, and alcohol use among college students during the COVID-19 pandemic

Charles, N.E., Strong, S.J., Burns, L.C., Bullerjahn, M.R., Serafine, K.M. 2021 Psychiatry Research



The COVID-19 pandemic caused significant disruption during the spring of 2020. Many college students were told to leave campus at spring break and to complete the semester remotely. This study evaluates effects of this disruption on student well-being. Measures of psychological symptoms, perceived stress, and alcohol use during the pandemic were completed by 148 students in spring 2020 and 352 students in fall 2020 at a university in the southeastern U.S. Results from both cohorts were compared to 240 students who completed the same measures in the fall 2019 semester. Participants in spring 2020 reported more mood disorder symptoms, perceived stress, and alcohol use than did pre-pandemic participants and worry about COVID-19 was negatively associated with well-being. By fall 2020 symptoms had largely returned to pre-pandemic levels. In general, White students reported a greater effect of the pandemic on well-being than did African American students. Young adults appear to be less vulnerable to the most serious medical complications associated with COVID-19, but nonetheless experience psychological effects from the pandemic. Universities and practitioners who work with college students can help young adults manage their symptoms and avoid behaviors like risky alcohol use when confronted with stressors such as the COVID-19 pandemic.


Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis

Karyotaki, E., Efthimiou, O., Miguel, C., (...), Spek, V., Forsell, Y. 2021 JAMA Psychiatry

78(4), pp. 361-371


Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.


Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

Zetterberg, H., Bendlin, B.B. 2021 Molecular Psychiatry

26(1), pp. 296-308


Clinical trial results presented in 2019 suggest that antibody-based removal of cerebral amyloid β (Aβ) plaques may possibly clear tau tangles and modestly slow cognitive decline in symptomatic Alzheimer’s disease (AD). Although regulatory approval of this approach is still pending, preparing the healthcare system for the advent of disease-modifying therapies against AD is imperative. In particular, it will be necessary to identify the most suitable biomarkers to facilitate appropriate treatment of AD. Here, we give an update on recent developments in fluid and imaging biomarkers for AD-related pathologies and discuss potential approaches that could be adopted to screen for and clarify the underlying pathology in people seeking medical advice because of cognitive symptoms. We succinctly review recent data regarding biomarkers for Aβ and tau pathology, neurodegeneration, synaptic dysfunction, and inflammation, highlight the need for further research into common copathologies, and suggest how different biomarkers could be used (most likely in combination) to facilitate the development and clinical implementation of novel drug candidates against AD.


The impact of quarantine on mental health status among general population in China during the COVID-19 pandemic

Wang, Y., Shi, L., Que, J., (...), Bao, Y., Shi, J. 2021 Molecular Psychiatry

26(9), pp. 4813-4822


Quarantine and isolation measures urgently adopted to control the COVID-19 pandemic might potentially have negative psychological and social effects. We conducted this cross-sectional, nationwide study to ascertain the psychological effect of quarantine and identify factors associated with mental health outcomes among population quarantined to further inform interventions of mitigating mental health risk especially for vulnerable groups under pandemic conditions. Sociodemographic data, attitudes toward the COVID-19, and mental health measurements of 56,679 participants from 34 provinces in China were collected by an online survey from February 28 to March 11, 2020. Of the 56,679 participants included in the study (mean [SD] age, 36.0 [8.2] years), 27,149 (47.9%) were male and 16,454 (29.0%) ever experienced home confinement or centralized quarantine during COVID-19 outbreak. Compared those without quarantine and adjusted for potential confounders, quarantine measures were associated with increased risk of total psychological outcomes (prevalence, 34.1% vs 27.3%; odds ratio [OR], 1.34; 95% CI, 1.28-1.39; P < 0.001). Multivariable logistic regression analyses showed that vulnerable groups of the quarantined population included those with pre-existing mental disorders or chronic physical diseases, frontline workers, those in the most severely affected areas during outbreak, infected or suspected patients, and those who are less financially well-off. Complying with quarantine, being able to take part in usual work, and having adequate understanding of information related to the outbreak were associated with less mental health issues. These results suggest that quarantine measures during COVID-19 pandemic are associated with increased risk of experiencing mental health burden, especially for vulnerable groups. Further study is needed to establish interventions to reduce mental health consequences of quarantine and empower wellbeing especially in vulnerable groups under pandemic conditions.


Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies

Solmi, M., Radua, J., Olivola, M., (...), Correll, C.U., Fusar-Poli, P. 2022 Molecular Psychiatry

27(1), pp. 281-295


Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11–34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7–16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9–25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14–29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15–23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17–48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20–41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20–34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20–33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21–46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.


Mental health responses to the COVID-19 pandemic: a latent class trajectory analysis using longitudinal UK data

Pierce, M., McManus, S., Hope, H., (...), Wessely, S., Abel, K.M. 2021 The Lancet Psychiatry

8(7), pp. 610-619


Background: The mental health of the UK population declined at the onset of the COVID-19 pandemic. Convenience sample surveys indicate that recovery began soon after. Using a probability sample, we tracked mental health during the pandemic to characterise mental health trajectories and identify predictors of deterioration. Methods: This study was a secondary analysis of five waves of the UK Household Longitudinal Study (a large, national, probability-based survey that has been collecting data continuously since January, 2009) from late April to early October, 2020 and pre-pandemic data taken from 2018–19. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). We used latent class mixed models to identify discrete mental health trajectories and fixed-effects regression to identify predictors of change in mental health. Findings: Mental health was assessed in 19 763 adults (≥16 years; 11 477 [58·1%] women and 8287 [41·9%] men; 3453 [17·5%] participants from minority ethnic groups). Mean population mental health deteriorated with the onset of the pandemic and did not begin improving until July, 2020. Latent class analysis identified five distinct mental health trajectories up to October 2020. Most individuals in the population had either consistently good (7437 [39·3%] participants) or consistently very good (7623 [37·5%] participants) mental health across the first 6 months of the pandemic. A recovering group (1727 [12·0%] participants) showed worsened mental health during the initial shock of the pandemic and then returned to around pre-pandemic levels of mental health by October, 2020. The two remaining groups were characterised by poor mental health throughout the observation period; for one group, (523 [4·1%] participants) there was an initial worsening in mental health that was sustained with highly elevated scores. The other group (1011 [7·0%] participants) had little initial acute deterioration in their mental health, but reported a steady and sustained decline in mental health over time. These last two groups were more likely to have pre-existing mental or physical ill-health, to live in deprived neighbourhoods, and be of Asian, Black or mixed ethnicity. Infection with SARS-CoV-2, local lockdown, and financial difficulties all predicted a subsequent deterioration in mental health. Interpretation: Between April and October 2020, the mental health of most UK adults remained resilient or returned to pre-pandemic levels. Around one in nine individuals had deteriorating or consistently poor mental health. People living in areas affected by lockdown, struggling financially, with pre-existing conditions, or infection with SARS-CoV-2 might benefit most from early intervention. Funding: None.


How COVID-19 Affects the Brain

Boldrini, M., Canoll, P.D., Klein, R.S. 2021 JAMA Psychiatry

78(6), pp. 682-683


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Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative

Karikari, T.K., Benedet, A.L., Ashton, N.J., (...), Blennow, K., Zetterberg, H. 2021 Molecular Psychiatry

26(2), pp. 429-442


Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer’s disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4–89.2%), as well as to distinguish between Aβ− and Aβ+ individuals along the Alzheimer’s continuum (AUC = 76.9%; 95% CI, 74.0–79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.

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