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  1. Tsutsumi A, Izutsu T, Ito A, Thornicroft G, Patel V, Minas H
    Lancet Psychiatry, 2015 Aug;2(8):679-680.
    PMID: 26249285 DOI: 10.1016/S2215-0366(15)00278-3
  2. Taquet M, Sillett R, Zhu L, Mendel J, Camplisson I, Dercon Q, et al.
    Lancet Psychiatry, 2022 Oct;9(10):815-827.
    PMID: 35987197 DOI: 10.1016/S2215-0366(22)00260-7
    BACKGROUND: COVID-19 is associated with increased risks of neurological and psychiatric sequelae in the weeks and months thereafter. How long these risks remain, whether they affect children and adults similarly, and whether SARS-CoV-2 variants differ in their risk profiles remains unclear.

    METHODS: In this analysis of 2-year retrospective cohort studies, we extracted data from the TriNetX electronic health records network, an international network of de-identified data from health-care records of approximately 89 million patients collected from hospital, primary care, and specialist providers (mostly from the USA, but also from Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan). A cohort of patients of any age with COVID-19 diagnosed between Jan 20, 2020, and April 13, 2022, was identified and propensity-score matched (1:1) to a contemporaneous cohort of patients with any other respiratory infection. Matching was done on the basis of demographic factors, risk factors for COVID-19 and severe COVID-19 illness, and vaccination status. Analyses were stratified by age group (age <18 years [children], 18-64 years [adults], and ≥65 years [older adults]) and date of diagnosis. We assessed the risks of 14 neurological and psychiatric diagnoses after SARS-CoV-2 infection and compared these risks with the matched comparator cohort. The 2-year risk trajectories were represented by time-varying hazard ratios (HRs) and summarised using the 6-month constant HRs (representing the risks in the earlier phase of follow-up, which have not yet been well characterised in children), the risk horizon for each outcome (ie, the time at which the HR returns to 1), and the time to equal incidence in the two cohorts. We also estimated how many people died after a neurological or psychiatric diagnosis during follow-up in each age group. Finally, we compared matched cohorts of patients diagnosed with COVID-19 directly before and after the emergence of the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529) variants.

    FINDINGS: We identified 1 487 712 patients with a recorded diagnosis of COVID-19 during the study period, of whom 1 284 437 (185 748 children, 856 588 adults, and 242 101 older adults; overall mean age 42·5 years [SD 21·9]; 741 806 [57·8%] were female and 542 192 [42·2%] were male) were adequately matched with an equal number of patients with another respiratory infection. The risk trajectories of outcomes after SARS-CoV-2 infection in the whole cohort differed substantially. While most outcomes had HRs significantly greater than 1 after 6 months (with the exception of encephalitis; Guillain-Barré syndrome; nerve, nerve root, and plexus disorder; and parkinsonism), their risk horizons and time to equal incidence varied greatly. Risks of the common psychiatric disorders returned to baseline after 1-2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days). By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period. Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94-1·10) or anxiety (1·00 [0·94-1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09-1·33] to 2·16 [1·46-3·19]). Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days). A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures. Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort). Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate. With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar.

    INTERPRETATION: This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.

    FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, The Wolfson Foundation, and MQ Mental Health Research.

  3. O'Connor RC, Worthman CM, Abanga M, Athanassopoulou N, Boyce N, Chan LF, et al.
    Lancet Psychiatry, 2023 Jun;10(6):452-464.
    PMID: 37182526 DOI: 10.1016/S2215-0366(23)00058-5
    Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international panel that used roadmapping methods and review evidence to identify key factors, mechanisms, and solutions for premature mortality across the social-ecological system. We identified 12 key overarching risk factors and mechanisms, with more commonalities than differences across the suicide and physical comorbidities domains. We also identified 18 actionable solutions across three organising principles: the integration of mental and physical health care; the prioritisation of prevention while strengthening treatment; and the optimisation of intervention synergies across social-ecological levels and the intervention cycle. These solutions included accessible, integrated high-quality primary care; early life, workplace, and community-based interventions co-designed by the people they should serve; decriminalisation of suicide and restriction of access to lethal means; stigma reduction; reduction of income, gender, and racial inequality; and increased investment. The time to act is now, to rebuild health-care systems, leverage changes in funding landscapes, and address the effects of stigma, discrimination, marginalisation, gender violence, and victimisation.
  4. Minas H, Izutsu T, Tsutsumi A, Kakuma R, Lopez AD
    Lancet Psychiatry, 2015 Mar;2(3):199-201.
    PMID: 26359888 DOI: 10.1016/S2215-0366(14)00124-2
  5. Izutsu T, Tsutsumi A, Minas H, Thornicroft G, Patel V, Ito A
    Lancet Psychiatry, 2015 Dec;2(12):1052-4.
    PMID: 26613844 DOI: 10.1016/S2215-0366(15)00457-5
  6. Austin A, De Silva U, Ilesanmi C, Likitabhorn T, Miller I, Sousa Fialho MDL, et al.
    Lancet Psychiatry, 2023 Dec;10(12):966-973.
    PMID: 37769672 DOI: 10.1016/S2215-0366(23)00265-1
    The effectiveness of mental health care can be improved through coordinated and wide-scale outcome measurement. The International Consortium for Health Outcomes Measurement has produced collaborative sets of outcome measures for various mental health conditions, but no universal guideline exists for eating disorders. This Position Paper presents a set of outcomes and measures for eating disorders as determined by 24 international experts from professional and lived experience backgrounds. An adapted Delphi technique was used, and results were assessed through an open review survey. Final recommendations suggest outcomes should be tracked across four domains: eating disorder behaviours and cognitions, physical health, co-occurring mental health conditions, and quality of life and social functioning. Outcomes are collected using three to five patient-reported measures. For children aged between 6 years and 12 years, the measures include the Children's Eating Attitude Test (or, for those with avoidant restrictive food intake disorder, the Eating Disorder in Youth Questionnaire), the KIDSCREEN-10, and the Revised Children's Anxiety and Depression Screener-25. For adolescents aged between 13 years and 17 years, the measures include the Eating Disorder Examination Questionnaire (EDE-Q; or, for avoidant restrictive food intake disorder, the Nine-Item Avoidant Restrictive Food Intake Disorder Screener [NIAS]), the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), the two-item Generalised Anxiety Disorder (GAD-2), the seven-item Generalised Anxiety Disorder (GAD-7), and the KIDSCREEN-10. For adults older than 18 years, measures include the EDE-Q (or, for avoidant restrictive food intake disorder, the NIAS), the PHQ-2, the PHQ-9, the GAD-2, the GAD-7, the Clinical Impairment Assessment, and the 12-item WHO Disability Assessment Schedule 2.0. These questionnaires should be supplemented by information on patient characteristics and circumstances (ie, demographic, historical, and clinical factors). International adoption of these guidelines will allow comparison of research and clinical interventions to determine which settings and interventions work best, and for whom.
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