Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

An Observational Study of Proactive and On-Request Psychiatry Consultation Services: Evidence for Differing Roles and Outcomes.

BACKGROUND: Proactive psychiatric consultation services rapidly identify and assess medical inpatients in need of psychiatric care. In addition to more rapid contact, proactive services may reduce the length of stay and improve staff satisfaction. However, in some settings, it is impractical to integrate a proactive consultation service into every hospital unit; on-request and proactive services are likely to coexist in the future. Prior research has focused on changes in outcomes with the implementation of proactive services. OBJECTIVE AND METHODS: This report describes differences between contemporary proactive and on-request services within the same academic medical center, comparing demographic and clinical data collected retrospectively from a 4-year period from the electronic medical record. RESULTS: The proactive service saw patients over four times as many initial admissions (7592 vs. 1762), but transitions and handoffs between services were common, with 434 admissions involving both services, comprising nearly 20% of the on-request service's total contacts. The proactive service admissions had a shorter length of stay and a faster time to first psychiatric contact, and the patients seen were more likely to be female, of Black race, and to be publicly insured. There were over three times as many admissions to psychiatry from the proactive service. The on-request service's admissions had a longer length of stay, were much more likely to involve intensive care unit services, surgical services, and transfers among units, and the patients seen were more likely to die in the hospital or to be discharged to subacute rehabilitation. CONCLUSIONS: Overall, the results suggest that the two services fulfill complementary roles, with the proactive service's rapid screening and contact providing care to a high volume of patients who might otherwise be unidentified and underserved. Simultaneously, the on-request service's ability to manage patients in response to consult requests over a much larger area of the hospital provided important support and continuity for patients with complex health needs. Institutions revising their consultation services will likely need to consider the best balance of these differing functions to address perceived demand for services.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Vigilance to Painful Laser Stimuli is Associated with Increased State Anxiety and Tense Arousal.

Introduction: Pain is frequently accompanied by enhanced arousal and hypervigilance to painful sensations. Here, we describe our findings in an experimental vigilance task requiring healthy participants to indicate when randomly timed moderately painful stimuli occur in a long train of mildly painful stimuli. Methods: During a continuous performance task with painful laser stimuli (CPTpain), 18 participants rated pain intensity, unpleasantness, and salience. We tested for a vigilance decrement over time using classical metrics including correct targets (hits), incorrectly identified non-targets (false alarms), hit reaction time, and false alarm reaction time. We measured state anxiety and tense arousal before and after the task. Results: We found a vigilance decrement across four 12.5-minute blocks of painful laser stimuli in hits [F3,51=2.91; p=0.043; time block 1>block 4 (t=2.77; p=0.035)]. Both self-report state anxiety (tpaired,17=3.34; p=0.0039) and tense arousal (tpaired,17=3.20; p=0.0053) increased after the task. We found a vigilance decrement during our laser pain vigilance task consistent with vigilance decrements found in other stimulus modalities. Furthermore, state anxiety positively correlated with tense arousal. Discussion: CPTpain acutely increased tense arousal and state anxiety, consistent with previous results implicating the reciprocal interaction of state anxiety and acute painful sensations and the role of pain in augmenting tense arousal. These results may indicate a psychological process which predisposes the hypervigilant to developing greater acute pain, resulting in positive feedback, greater pain and anxiety.

Prevalence and correlates of lifetime suicide attempt in obsessive-compulsive disorder with major depression.

BACKGROUND: Little is known about specific obsessive-compulsive clinical features associated with lifetime history of suicide attempt in individuals with obsessive-compulsive disorder (OCD) and major depression. METHODS: The study sample included 515 adults with OCD and a history of major depression. In exploratory analyses, we compared the distributions of demographic characteristics and clinical features in those with and without a history of attempted suicide and used logistic regression to evaluate the association between specific obsessive-compulsive clinical features and lifetime suicide attempt. RESULTS: Sixty-four (12%) of the participants reported a lifetime history of suicide attempt. Those who had attempted suicide were more likely to report having experienced violent or horrific images (52% vs. 30%; p < 0.001). The odds of lifetime suicide attempt were more than twice as great in participants with versus without violent or horrific images (O.R. = 2.46, 95%, CI = 1.45-4.19; p < 0.001), even after adjustment for other risk correlates of attempted suicide, including alcohol dependence, post-traumatic stress disorder, parental conflict, excessive physical discipline, and number of episodes of depression. The association between violent or horrific images and attempted suicide was especially strong in men, 18-29 year olds, those with post-traumatic stress disorder, and those with particular childhood adversities. CONCLUSIONS: Violent or horrific images are strongly associated with lifetime suicide attempts in OCD-affected individuals with a history of major depression. Prospective clinical and epidemiological studies are needed to elucidate the basis of this relationship.

Outpatient Mental Health Follow-up and Recurrent Self-harm and Suicide Among Patients Admitted to the ICU for Self-harm: A Population-based Cohort Study.

BACKGROUND: Patients surviving an ICU admission for deliberate self-harm are at high risk of recurrent self-harm or suicide after discharge. It is unknown whether mental health follow-up after discharge (with either a family physician or psychiatrist) reduces this risk. RESEARCH QUESTION: What is the association between mental health follow-up after discharge and recurrent self-harm among patients admitted to the ICU for intentional self-harm? STUDY DESIGN AND METHODS: Population-based cohort study of consecutive adults (≥ 18 years of age) from Ontario, Canada, who were admitted to ICU because of intentional self-harm between 2009 and 2017. We categorized patients according to follow-up, with 'early follow-up' indicating 1 to 21 days after discharge, 'late follow-up' indicating 22 to 60 days after discharge, and 'no follow-up' indicating no follow-up within 60 days of discharge. We conducted analyses using a cause-specific extended Cox regression model to account for varying time for mental health follow-up relative to the outcomes of interest. The primary outcome was recurrent ICU admission for self-harm within 1 year of discharge. RESULTS: We included 9,569 consecutive adults admitted to the ICU for deliberate self-harm. Compared with receiving no mental health follow-up, both early follow-up (hazard ratio [HR], 1.37; 95% CI, 1.07-1.75) and late follow-up (HR, 1.69; 95% CI, 1.22-2.35) were associated with increased risk in recurrent ICU admission for self-harm. As compared with no follow-up, neither early follow-up (HR, 1.10; 95% CI, 0.70-1.73) nor late follow-up (HR, 1.54; 95% CI, 0.84-2.83) were associated with increased risk of death by suicide. INTERPREATION: Among adults admitted to the ICU for deliberate self-harm, mental health follow-up after discharge was not associated with reduced risk of recurrent ICU admission for self-harm or death resulting from suicide, and patients seeking outpatient follow-up may be those at highest risk of these outcomes. Future research should focus on additional and novel methods of risk mitigation in this vulnerable population.

Psychiatric comorbidity in the Baltimore ECA follow-up study: the matrix approach.

BACKGROUND: Psychiatric comorbidity is defined as the joint occurrence of two or more mental or substance use disorders. Widespread psychiatric comorbidity has been reported in treatment and population-based studies. The aim of this study was to measure the extent and impact of psychiatric comorbidity in a cohort of the Baltimore Epidemiologic Catchment Area study. METHODS: We examined the comorbidity burden of 16 mental disorders in a cohort of 847 participants using both established and novel analytical approaches The Comorbidity to Diagnosis Inflation Ratio (CDIR), is a statistical instrument that quantifies impact of pairwise comorbid associations, both on the whole sample, as well as on each specific disorder. RESULTS: Most anxiety disorders had substantial co-occurrence with each other, as well as with Major Depressive Disorder (MDD). In addition, mood disorders had a high degree of comorbidity with Alcohol Dependence (AD). The CDIR for the whole sample was 1.32, indicating a ratio of 132 comorbidities per 100 diagnoses. The conditions with high sample prevalence were relatively less comorbid than the low prevalence conditions. Obsessive Compulsive Disorder had a comorbidity burden that was 89% greater than the overall sample. CONCLUSION: Anxiety disorders are highly interrelated, as well as highly comorbid with depression. The comorbidity phenomenon is linked to the differential prevalence of the analyzed conditions. Comorbidity frequency (most prevalent comorbid condition) appears mutually exclusive to comorbidity burden (most widely interrelated condition). While AD and MDD were the most frequently diagnosed disorders; low prevalence conditions as OCD and GAD were the most widely interrelated.

Association of Extracorporeal Membrane Oxygenation With New Mental Health Diagnoses in Adult Survivors of Critical Illness.

Importance: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in critically ill patients, but little is known regarding long-term psychiatric sequelae among survivors after ECMO. Objective: To investigate the association between ECMO survivorship and postdischarge mental health diagnoses among adult survivors of critical illness. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, from April 1, 2010, through March 31, 2020. Adult patients (N=4462; age ≥18 years) admitted to the intensive care unit (ICU), and surviving to hospital discharge were included. Exposures: Receipt of ECMO. Main Outcomes and Measures: The primary outcome was a new mental health diagnosis (a composite of mood disorders, anxiety disorders, posttraumatic stress disorder; schizophrenia, other psychotic disorders; other mental health disorders; and social problems) following discharge. There were 8 secondary outcomes including incidence of substance misuse, deliberate self-harm, death by suicide, and individual components of the composite primary outcome. Patients were compared with ICU survivors not receiving ECMO using overlap propensity score-weighted cause-specific proportional hazard models. Results: Among 642 survivors who received ECMO (mean age, 50.7 years; 40.7% female), median length of follow-up was 730 days; among 3820 matched ICU survivors who did not receive ECMO (mean age, 51.0 years; 40.0% female), median length of follow-up was 1390 days. Incidence of new mental health conditions among survivors who received ECMO was 22.1 per 100-person years (95% confidence interval [CI] 19.5-25.1), and 14.5 per 100-person years (95% CI, 13.8-15.2) among non-ECMO ICU survivors (absolute rate difference of 7.6 per 100-person years [95% CI, 4.7-10.5]). Following propensity weighting, ECMO survivorship was significantly associated with an increased risk of new mental health diagnosis (hazard ratio [HR] 1.24 [95% CI, 1.01-1.52]). There were no significant differences between survivors who received ECMO vs ICU survivors who did not receive ECMO in substance misuse (1.6 [95% CI, 1.1 to 2.4] per 100 person-years vs 1.4 [95% CI, 1.2 to 1.6] per 100 person-years; absolute rate difference, 0.2 per 100 person-years [95% CI, -0.4 to 0.8]; HR, 0.86 [95% CI, 0.48 to 1.53]) or deliberate self-harm (0.4 [95% CI, 0.2 to 0.9] per 100 person-years vs 0.3 [95% CI, 0.2 to 0.3] per 100 person-years; absolute rate difference, 0.1 per 100 person-years [95% CI, -0.2 to 0.4]; HR, 0.68 [95% CI, 0.21 to 2.23]). There were fewer than 5 total cases of death by suicide in the entire cohort. Conclusions and Relevance: Among adult survivors of critical illness, receipt of ECMO, compared with ICU hospitalization without ECMO, was significantly associated with a modestly increased risk of new mental health diagnosis or social problem diagnosis after discharge. Further research is necessary to elucidate the potential mechanisms underlying this relationship.

Baseline Anxiety and Depression and Risk for ICU Delirium: A Prospective Cohort Study.

OBJECTIVES: Anxiety and depression are common mental disorders in adults admitted to the ICU. Although depression increases postsurgical delirium and anxiety does not, their associations with ICU delirium in critically ill adults remain unclear. We evaluated the association between ICU baseline anxiety and depression and ICU delirium occurrence. DESIGN: Subgroup analysis of a prospective cohort study. SETTING: Single, 36-bed mixed ICU. PATIENTS: Nine-hundred ninety-one ICU patients admitted with or without delirium between July 2016 and February 2020; patients admitted after elective surgery or not assessed for anxiety/depression were excluded. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTs: The Hospital Anxiety and Depression Scale questionnaire was administered at ICU admission to determine baseline anxiety and depression. All patients were assessed with the Confusion Assessment Method for the ICU (CAM-ICU) q8h; greater than or equal to 1 +CAM-ICU assessment and/or scheduled antipsychotic use represented a delirium day. Multivariable logistic and Quasi-Poisson regression models, adjusted for ICU days and nine delirium risk variables ("Pre-ICU": age, Charlson Comorbidity Index, cognitive impairment; "ICU baseline": Acute Physiology and Chronic Health Evaluation-IV, admission type; "Daily ICU": opioid and/or benzodiazepine use, Sequential Organ Failure Assessment score, coma), were used to evaluate associations between baseline anxiety and/or depression and ICU delirium. Among the 991 patients, 145 (14.6%) had both anxiety and depression, 78 (7.9%) had anxiety only, 91 (9.2%) had depression only, and 677 (68.3%) had neither. Delirium occurred in 406 of 991 total cohort (41.0%) patients; in the baseline anxiety and depression group, it occurred in 78 of 145 (53.8%), in the anxiety only group, 37 of 78 (47.4%), in the depression only group, 39 of 91 (42.9%), and in the group with neither in 252 of 677 (37.2%). Presence of both baseline anxiety and depression was associated with greater delirium occurrence (adjusted odds ratio, 1.99; 95% CI, 1.10-3.53; p = 0.02) and duration (adjusted risk ratio, 1.62; 95% CI, 1.17-2.23; p < 0.01). CONCLUSIONS: Baseline anxiety and depression are associated with increased ICU delirium occurrence and should be considered when delirium risk reduction strategies are being formulated.

A Cross-Sectional Time Course of COVID-19 Related Worry, Perceived Stress, and General Anxiety in the Context of Post-Traumatic Stress Disorder-like Symptomatology.

The COVID-19 pandemic within the United States of America resulted in over 800,000 deaths as of February 2022 and has been addressed by social distancing or stay-at-home measures. Collective prolonged multimodal trauma on this scale is likely to elicit symptomatology in the general population consistent with post-traumatic stress disorder (PTSD), somatization, anxiety, and stress. The psychological component of this response contributes substantially to the burden of this disease worldwide. This cross-sectional study examines the relationship between COVID-19-related concern, anxiety, and perceived stress on PTSD-like symptomatology over the course of the COVID-19 pandemic. Participants were recruited via social media within the United States of America between 8th May 2020 and 11th August 2021 to complete an internet questionnaire including mood, personality, and COVID-19-specific scales. General anxiety and PTSD-like symptomatology were above the screening cutoffs for most respondents. These measures increased in severity over the pandemic, with the change point of our Concern scale preceding that of the other significant measures. Measures of COVID-19-related concern, generalized anxiety, and PTSD-like symptomatology were strongly correlated with each other. Anxiety, perceived stress, and PTSD-like symptomatology are strongly interrelated, increase with pandemic length, and are linked to reported levels of concern over COVID-19. These observations may aid future research and policy as the pandemic continues.

The association between traumatic life events and insomnia symptoms among men and women: Results from the Baltimore Epidemiologic Catchment Area follow-up study.

STUDY OBJECTIVES: Trauma exposure likely contributes to poor sleep, but relatively few studies have empirically tested this, instead focusing on posttraumatic stress disorder. Moreover, little is known about sex differences in sleep after trauma. The current study used a cross-sectional and retrospective design to test hypotheses that trauma exposure would be associated with subsequent insomnia symptoms, particularly among women, even after accounting for important covariates. METHOD: Data from Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area Study (N = 1920) were used to examine associations between remote (prior to past year) and recent (past year) trauma and current sleep disturbance (insomnia, hypersomnia symptoms) in the total sample (Mage= 55, 63.2% women, 57.7% white), and separately in men and women. Sensitivity analyses were conducted among individuals with no pretrauma sleep disturbance to examine incident sleep disturbance. RESULTS: Among all participants, both remote (odds ratio [OR] = 1.95, 95% confidence interval [CI] [1.34, 2.85]) and recent (OR = 1.94, 95% CI [1.31, 2.87]) trauma exposure were associated with increased odds of insomnia (OR = 2.41, 95% CI [1.54, 3.76]) but not hypersomnia. Associations between trauma and insomnia were particularly strong among women, but null among men. The relationship between trauma exposure and insomnia symptoms persisted among individuals with no pretrauma history of insomnia. CONCLUSION: Results suggest women may be vulnerable to insomnia symptoms as sequelae of trauma. Future research should examine prospective associations between trauma and sleep in larger samples and how assessment and treatment of insomnia among women trauma survivors reduces the public health impact of trauma and poor sleep.

An investigation of COVID-19 related worry in a United States population sample.

BACKGROUND: Although general anxiety has increased markedly since the onset of the COVID-19 pandemic, little has been reported about the demographic distribution of COVID-19 related worry, its relationship with psychological features, and its association with depression symptoms in the United States (US). METHODS: 2117 participants, selected to represent the age, gender, and race/ethnic distributions of the US population, completed an online survey. Analysis of variance and correlation analyses were used to assess relationships between the COVID-19 related worry score and demographic characteristics, past psychiatric diagnoses, personality dimensions, and current psychological symptoms. Logistic regression was used to evaluate the association between the COVID-19 worry score and depression symptoms. RESULTS: The COVID-19 worry score was markedly higher in younger (18-49 year-olds) than older participants, and moderately higher in men, those who were married or cohabiting, with post-college education, and/or living in large urban areas. The COVID-19 worry score also was markedly higher in those who reported having been diagnosed with a psychiatric disorder. The COVID-19 worry score correlated with neuroticism, current psychological symptoms, and COVID-19 risk and COVID-19 behavior scores. The COVID-19 worry score was associated with current depression symptoms (OR = 1.10, 95% CI = 1.09-1.11; p < 0.001) in univariable models and remained significant after adjustment for other correlates of depression, including COVID-19 risk. CONCLUSIONS: In this US sample, the COVID-19 worry score was inversely related to age, strongly related to psychological symptoms, and independently associated with depression symptoms. These findings have implications for the community mental health response to the COVID-19 pandemic in the US.

The 5-year pre- and post-hospitalization treated prevalence of mental disorders and psychotropic medication use in critically ill patients: a Canadian population-based study.

PURPOSE: The interplay between critical illness and mental disorders is poorly understood. The purpose of this study is to measure both the treated prevalence of mental disorders and psychotropic medication use before and after hospitalization and the impact of intensive care unit (ICU) admission on these outcomes. METHODS: Using a population-based administrative database in Manitoba, Canada, 49,439 ICU patients admitted between 2000 and 2012 were compared to two matched comparison groups (hospitalized; n = 146,968 and general population; n = 141,937). Treated prevalence of mental disorders and psychotropic medication prescriptions were measured in the 5-year periods before and after the hospitalization. Multivariable models compared adjusted prevalence ratios (APRs) between populations. RESULTS: The 5-year treated mental disorder prevalence in the ICU population increased from 41.5% pre-hospitalization to 55.6% post-hospitalization. Compared to non-ICU hospitalized patients, the adjusted treated mental disorder prevalence in ICU patients was lower prior to hospitalization (1-year APR 0.94, 95% CI 0.92-0.97, p < 0.0001; 5-year APR 0.99, 95% CI 0.98-1.00, p = 0.1), but higher following discharge (1-year APR 1.08, 95% CI 1.05-1.11, p < 0.0001, 5-year APR 1.03, 95% CI 1.01-1.05, p < 0.0001). A high proportion of ICU patients received antidepressant, anxiolytic and sedative-hypnotic prescriptions before and after their hospitalization. In multivariable analyses, ICU exposure was associated with an increase in mood, anxiety and psychotic disorders, and sedative-hypnotics use (p < 0.0001 for all Time × Group interactions). CONCLUSIONS: During the 5 years after admission to ICU, there is a significant increase in treated prevalence of mental disorders and psychotropic medication use compared to the 5 years prior to ICU and compared to general population and hospital cohorts. Prevention and intervention programs that identify and treat mental disorders among survivors of critical illness warrant further study.

Virtual Reality to Improve Sequelae of the Postintensive Care Syndrome: A Multicenter, Randomized Controlled Feasibility Study.

Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU-related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients' self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health. DESIGN: A multicenter, randomized controlled feasibility study. SETTING: ICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands. PATIENTS: Consecutive mechanically ventilated patients with sepsis or septic shock. INTERVENTIONS: Patients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group). MEASUREMENT AND MAIN RESULTS: Explorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5-21 d) after ICU discharge, and one session (median, 95% range, 1-6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36-67] vs control virtual reality, 47 [26-63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life. CONCLUSIONS: ICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.

Psychologic Distress and Quality of Life After ICU Treatment for Coronavirus Disease 2019: A Multicenter, Observational Cohort Study.

To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors. DESIGN: A prospective, observational cohort study. SETTING: Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands. PATIENTS: Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic. MEASURES AND MAIN RESULTS: The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36-77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0-17] vs 5 [0-16]; estimated mean difference 2.3 [95% CI, 0.0-4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0-15] vs 5 [0-16]; estimated mean difference 2.4 [95% CI, 0.1-2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population. CONCLUSIONS: Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.

Exome sequencing in obsessive-compulsive disorder reveals a burden of rare damaging coding variants.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of affected individuals) and describe contributions to disease risk from rare damaging coding variants. In case-control analyses (n = 1,263/11,580), the most significant single-gene result was observed in SLITRK5 (odds ratio (OR) = 8.8, 95% confidence interval 3.4-22.5, P = 2.3 × 10-6). Across the exome, there was an excess of loss of function (LoF) variation specifically within genes that are LoF-intolerant (OR = 1.33, P = 0.01). In an analysis of trios, we observed an excess of de novo missense predicted damaging variants relative to controls (OR = 1.22, P = 0.02), alongside an excess of de novo LoF mutations in LoF-intolerant genes (OR = 2.55, P = 7.33 × 10-3). These data support a contribution of rare coding variants to OCD genetic risk.

Suicide and self-harm in adult survivors of critical illness: population based cohort study.

OBJECTIVE: To analyse the association between survival from critical illness and suicide or self-harm after hospital discharge. DESIGN: Population based cohort study using linked and validated provincial databases. SETTING: Ontario, Canada between January 2009 and December 2017 (inclusive). PARTICIPANTS: Consecutive adult intensive care unit (ICU) survivors (≥18 years) were included. Linked administrative databases were used to compare ICU hospital survivors with hospital survivors who never required ICU admission (non-ICU hospital survivors). Patients were categorised based on their index hospital admission (ICU or non-ICU) during the study period. MAIN OUTCOME MEASURES: The primary outcome was the composite of death by suicide (as noted in provincial death records) and deliberate self-harm events after discharge. Each outcome was also assessed independently. Incidence of suicide was evaluated while accounting for competing risk of death from other causes. Analyses were conducted by using overlap propensity score weighted, cause specific Cox proportional hazard models. RESULTS: 423 060 consecutive ICU survivors (mean age 61.7 years, 39% women) were identified. During the study period, the crude incidence (per 100 000 person years) of suicide, self-harm, and the composite of suicide or self-harm among ICU survivors was 41.4, 327.9, and 361.0, respectively, compared with 16.8, 177.3, and 191.6 in non-ICU hospital survivors. Analysis using weighted models showed that ICU survivors (v non-ICU hospital survivors) had a higher risk of suicide (adjusted hazards ratio 1.22, 95% confidence interval 1.11 to 1.33) and self-harm (1.15, 1.12 to 1.19). Among ICU survivors, several factors were associated with suicide or self-harm: previous depression or anxiety (5.69, 5.38 to 6.02), previous post-traumatic stress disorder (1.87, 1.64 to 2.13), invasive mechanical ventilation (1.45, 1.38 to 1.54), and renal replacement therapy (1.35, 1.17 to 1.56). CONCLUSIONS: Survivors of critical illness have increased risk of suicide and self-harm, and these outcomes were associated with pre-existing psychiatric illness and receipt of invasive life support. Knowledge of these prognostic factors might allow for earlier intervention to potentially reduce this important public health problem.