Day and night light exposure are associated with psychiatric disorders: an objective light study in >85,000 people Nature.com
Largest ever study on light exposure proves its impact on mental health Medical Xpress
Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales The Lancet
Exposure to light at night found to increase risk of depression by 30% New Atlas
‘Almost like injecting a drug’: Sunlight seems to protect us from depression, anxiety Sydney Morning Herald
Summary: While neuroimaging holds great potential in helping researchers link specific patterns of brain activity to mental health disorders, a new study finds there is still a way to go to effectively link neuroimaging results to specific mental health disorders.
Source: Yale
Neuroimaging technology has been shown to hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new Yale-led study shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).
Their findings are published Jan. 11 in the American Journal of Psychiatry.
Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.
“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.
For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which Emory and Harvard scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at U.S. emergency departments following traumatic events.
Specifically, when researchers measured patients’ brain activity during the performance of simple tasks — including ones that probe responses to threats and rewards — they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.
While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms. Image is in the public domain
However, when Yale researchers analyzed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.
“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalize across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.
See also
In fact, Yale researchers are currently working with the investigators of the original Emory-Harvard study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.
“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”
About this neuroimaging and mental health research news
Author: Bess Connolly Source: Yale Contact: Bess Connolly – Yale Image: The image is in the public domain
Original Research: The findings will appear in American Journal of Psychiatry
Summary: 47% of patients with a mental health disorder receive a different diagnosis within the first ten years of receiving their initial diagnosis.
Source: University of Copenhagen
“Let’s see how things go.”
So psychiatrists often say to one another after a patient has been diagnosed with the first disorder – not because the diagnosis is not correct, but because psychiatrists know that psychiatric diagnoses have a tendency to change over the years.
In fact, 47 percent of psychiatric patients are diagnosed with a different diagnosis within 10 years of receiving their first diagnosis.
This is the result of a new study mapping the diagnostic development of more than 180,000 psychiatric patients in Denmark.
One of the researchers behind the study is Clinical Research Associate Professor at the Department of Clinical Medicine Anders Jørgensen. He is not surprised by the results of the study.
“Mental disorders are dynamic. They change over the course of a life. Therefore, I am not surprised by the relatively great diagnostic development in these patients,” says Anders Jørgensen.
The study shows which development is probable and which is improbable for the 20 most common mental diagnoses. The most uncertain, i.e., the ones that are most likely to change, include the diagnoses acute psychosis, addiction and depression.
The most certain, i.e. the ones that are least likely to change, include the diagnoses functional disabilities, which are long-term physical disabilities with no physical cause, eating disorders and sexual disorders such as reduced sexual interest or erectile dysfunction with no physical cause.
The study is useful from the moment a patient is diagnosed with his or her first disorder, as it enables doctors to look up the 10-year diagnostic development of other patients.
“Doctors wanting to plan the right course of treatment and be able to tell patients what they can expect need these figures. Ultimately, we hope it can help improve treatment and ensure evidence-based follow-up. The more you know about the probable course of illness, the better the treatment is likely to be,” says Anders Jørgensen.
The study is limited to patients treated in the psychiatric healthcare system. This means that the people who go to their GP and are referred to a psychologist are not included in the study.
“We only look at people who have been diagnosed in psychiatric hospitals and who typically experience more severe courses of illness than those who make an appointment with their GP,” says Anders Jørgensen.
Depression is one of the most uncertain diagnoses
Among the three most common diagnoses analysed in the study, patients diagnosed with a single episode of depression have the highest risk of being diagnosed with a new disorder within 10 years.
“According to the study, patients with this diagnosis have a 60-percent chance of being diagnosed with a new disorder within 10 years,” says Associate Professor Terese Sara Høj Jørgensen from the Section of Social Medicine at the Department of Public Health.
But numbers can be deceiving. Because the majority (20 percent) of those diagnosed with a single episode of depression is subsequently diagnosed with periodic depression, which is the name for recurring depressions.
“It is not surprising that a single episode of depression can develop into recurring depressions,” says Anders Jørgensen.
The study shows which development is probable and which is improbable for the 20 most common mental diagnoses. Image is in the public domain
Next to periodic depression, personality disorder and stress reaction disorders are the diagnoses most likely to follow a depression diagnosis. A stress reaction disorder is when a major incident such as divorce or death causes the patient to develop a mental disorder resembling stress or depression.
Anders Jørgensen hopes the new data can help improve treatment for people who suffer a depression.
“Unlike patients who experience their first psychosis, we currently have no uniform treatment option for patients who experience their first depression. We may look into developing such an option, and our figures can support the development of effective treatment,” says Anders Jørgensen.
What did the study entail?
Using Danish register data, the researchers identified psychiatric patients aged 18 years or more diagnosed with one of the 20 most common mental disorders. This gave them a group of 184,949 individuals.
The researchers looked at how the patients’ diagnoses have change since the first diagnosis was given. They used so-called sequence analysis to analyse the development.
Typical development for the three most common diagnoses analysed in the study
Depression: 60 percent of those diagnosed with a single depressive episode are diagnosed with a new disorder within 10 years. 20 percent develop periodic depression, 10 percent a stress disorder and six percent a personality disorder.
See also
Addiction: 52 percent are diagnosed with a new disorder within 10 years. Eight percent develop a stress disorder, five percent a personality disorder and five percent schizophrenia. The category includes all addiction diagnoses such as alcohol, opioid, cannabis etc. Some forms of addiction are more uncertain than others.
Stress reaction disorder: 36 percent are diagnosed with a new disorder within 10 years. Eight percent develop a single depressive episode, seven percent a personality disorder and six percent periodic depression.
About this mental health research news
Author: Liva Polack Source: University of Copenhagen Contact: Liva Polack – University of Copenhagen Image: The image is in the public domain
Original Research: Closed access. “Mapping diagnostic trajectories from the first hospital diagnosis of a psychiatric disorder: a Danish nationwide cohort study using sequence analysis” by Anders Jørgensen et al. Lancet Psychiatry
Abstract
Mapping diagnostic trajectories from the first hospital diagnosis of a psychiatric disorder: a Danish nationwide cohort study using sequence analysis
Background
A key clinical problem in psychiatry is predicting the diagnostic future of patients presenting with psychopathology for the first time. The objective of this study was to establish a comprehensive map of subsequent diagnoses after a first psychiatric hospital diagnosis.
Methods
Through the Danish National Patient Registry, we identified patients aged 18 years or older with an inpatient or outpatient psychiatric hospital contact and who had received one of the 20 most common first-time psychiatric diagnoses (defined at the ICD-10 two-cipher level, F00–F99) between Jan 1, 1995, and Dec 31, 2008. For each first-time diagnosis, the 20 most frequent subsequent psychiatric diagnoses (F00–F99), and death, occurring during 10 years of follow-up were identified as outcomes. To assess diagnostic stability, we used social sequence analyses, assigning a subsequent diagnosis to each state with a length of 6 months following each first-time diagnosis. The subsequent diagnosis was defined as the last diagnosis given within each 6-month period. We calculated the normalised entropy of each sequence to show the uncertainty of predicting the states in a given sequence. Cox proportional hazards models were used to assess the risk of receiving a subsequent diagnosis (at the one-cipher level, F0–F9) after each first-time diagnosis.
Findings
The cohort consisted of 184 949 adult patients (77 129 [41·7%] men and 107 820 [58·3%] women, mean age 42·5 years [SD 18·5; range 18 to >100). Ethnicity data were not recorded. Over 10 years of follow-up, 86 804 (46·9%) patients had at least one subsequent diagnosis that differed from their first-time diagnosis. Measured by mean normalised entropy values, persistent delusional disorders (ICD-10 code F22), mental and behavioural disorders due to multiple drug use and use of other psychoactive substances (F19), and acute and transient psychotic disorders (F23) had the highest diagnostic variability, whereas eating disorders (F50) and non-organic sexual dysfunction (F52) had the lowest. The risk of receiving a subsequent diagnosis with a psychiatric disorder from an ICD-10 group different from that of the first-time diagnosis varied substantially among first-time diagnoses.
Interpretation
These data provide detailed information on possible diagnostic outcomes after a first-time presentation in a psychiatric hospital. This information could help clinicians to plan relevant follow-up and inform patients and families on the degree of diagnostic uncertainty associated with receiving a first psychiatric hospital diagnosis, as well as likely and unlikely trajectories of diagnostic progression.
Funding
Mental Health Services, Capital region of Denmark.
Translation
For the Danish translation of the abstract see Supplementary Materials section.
As women burn headscarves and cut off their hair in nationwide protests, an Iranian official on Tuesday said that school students participating in street protests are being detained and taken to mental health institutions.
In an interview with an independent reformist Iranian newspaper, Iran’s Education Minister Yousef Nouri confirmed that some school students have indeed been detained and referred to what he called “psychological institutions.”
The establishments holding the students, he said, are meant to reform and reeducate the students to prevent “anti-social” behavior.
“It is possible these students have become ‘anti-social characters’ and we want to reform them,” he told the Shargh newspaper, adding that the students “can return to class after they’ve been reformed.”
Nearly a month ago, 22-year-old Mahsa Amini died after being taken to a “reeducation center” by state “morality police” for not abiding by the state’s conservative dress code. Amini’s death has sparked weeks of anti-government protests that have spread across the country.
The education minister could not put an exact figure on the number of detained students, saying “the number is not a lot and there are not many.”
Girls and women across Iran have played a vital role in the demonstrations, and in recent weeks have protested at schools, university campuses and out on the streets.
Footage circulated across social media has showed Iranian women and girls chanting “death to the dictator” as they take off their headscarves; on one occasion, CNN witnessed girls from a vocational high school in Tehran protesting on a street near their school and chanting, “woman, life, freedom.”
The demonstrations have, at times, turned dangerous. Police fired tear gas on protesters in Tehran on Wednesday, and book shops and offices near Tehran University shut their doors as anti-riot police chased and fired rubber bullets on demonstrators, an eyewitness said. In Kaj Square, members of Iran’s Basij paramilitary organization ordered people to move along and stopped others from standing on the streets, according to the eyewitness.
Videos obtained by the pro-reform activist outlet IranWire posted on social media on Wednesday showed demonstrations across Tehran and other Iranian cities.
Police and Basij members fired tear gas at the gathering of Iranian lawyers in Tehran, while uniformed and plainclothes police were seen firing weapons in the air in West Tehran, dispersing people from the scene. In one of the busiest shopping streets in the city, riot police were seen gathering. In another, protesters chanted “Mullahs, get lost.”
Footage from Rasht, northwest of Tehran, showed police wearing riot gear beating people with batons and pulling them from the sidewalk
On Tuesday, the United Nations’ children’s agency UNICEF called for the protection of children and adolescents amid public unrest in Iran, which is now in its third week.
“We are extremely concerned by continuing reports of children and adolescents being killed, injured and detained amid the ongoing public unrest in Iran,” read the UNICEF statement.
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.
Introduction
Since the early stages of the pandemic, COVID-19 has been known to be associated with an increased risk of many neurological and psychiatric sequelae.
1
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Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
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High-dimensional characterization of post-acute sequelae of COVID-19.
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However, more than 2 years after the first case was diagnosed, three important questions remain unanswered.
First, we do not know if or when the risks of different post-COVID-19 outcomes return to baseline. This information is important to patients (who want to know when they can stop worrying about potential complications of their SARS-CoV-2 infection), clinicians (who need to know whether a clinical presentation is plausibly attributable to a post-COVID condition), and health policy makers (who must plan appropriate service provision). Previous studies on the neurological and psychiatric sequelae of COVID-19 did not investigate this question.
3
High-dimensional characterization of post-acute sequelae of COVID-19.
,
4
Taquet M
Geddes JR
Husain M
Luciano S
Harrison PJ
6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.
,
5
Daugherty SE
Guo Y
Heath K
et al.
Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study.
,
6
Risks of mental health outcomes in people with COVID-19: cohort study.
One study estimated the prevalence of self-reported anxiety, depressive, and sleep symptoms at 2, 2–6, and 6–16 months after COVID-19 diagnosis and found that the prevalence of depressive symptoms, but not sleep symptoms, decreased over time.
7
Magnúsdóttir I
Lovik A
Unnarsdóttir AB
et al.
Acute COVID-19 severity and mental health morbidity trajectories in patient populations of six nations: an observational study.
Although informative, the self-reported nature of these findings and the restricted range of outcomes measured limit their usefulness for clinical practice and for informing public health policies.
Research in context
Evidence before this study
We searched PubMed (Medline) on March 21, 2022, for publications since database inception in English using the terms “(neuropsychiatr*[Title/Abstract] OR neurologic*[Title/Abstract] OR psychiatric[Title/Abstract] OR depress*[Title/Abstract] OR anxiety*[Title/Abstract] OR cognit*[Title/Abstract] OR brain[Title/Abstract]) AND (variant*[Title/Abstract] OR omicron[Title/Abstract] OR delta[Title/Abstract] OR evolution[Title/Abstract]) AND (COVID[Title/Abstract] OR COVID-19[Title/Abstract] OR SARS*[Title/Abstract])”. We found cohort studies and systematic reviews reporting neuropsychiatric sequelae persisting up to 10 months after COVID-19. We found one large, 6-month electronic health records study of neuropsychiatric disorders after a COVID-19 diagnosis. This study reported increased incidence and relative risk of cognitive symptoms and anxiety or depression 6 months after COVID-19, compared with influenza. We are not aware of any large-scale data regarding long-term COVID-19 sequelae beyond 12 months, or the evolution of incidence or relative risk of neuropsychiatric diagnoses in patients recovered from COVID-19 throughout the pandemic, stratified by COVID-19 variant or vaccination status.
Added value of this study
To our knowledge, this is the first study with a comparator cohort that assesses the risks of a range of neurological and psychiatric outcomes of COVID-19 up to 2 years after the index SARS-CoV-2 infection. We found that the risks of post-COVID neurological and psychiatric outcomes follow different trajectories: the risk of cognitive deficit, dementia, psychotic disorder, and epilepsy or seizures remain elevated 2 years after SARS-CoV-2 infection, while the risks of other diagnoses (notably, mood and anxiety disorders) subside after 1–2 months and show no overall excess over the whole 2-year follow-up. We also found that risk trajectories differ somewhat in children: they are not at an increased risk of mood or anxiety disorders (even over the first 6 months) and their risk of cognitive deficit is transient, but they share adults’ risk of several other diagnoses and are notably at risk of epilepsy or seizures. Finally, we found that the risks of neurological and psychiatric outcomes remain similar after the emergence of the omicron (B.1.1.529) variant as with the delta (B.1.617.2) variant, but are offset by a significantly lower death rate.
Implications of all the available evidence
The persisting increased risk of post-COVID-19 cognitive deficit, dementia, psychotic disorders, and epilepsy or seizures 2 years after the index infection calls for enhanced service provision to diagnose and manage these sequelae, and research to understand the mechanisms. The differing profile of post-COVID-19 neurological and psychiatric diagnoses in children informs the risk–benefit association of policies aimed at preventing COVID-19 in paediatric populations and suggests that underlying mechanisms might in part be different from those in adults. The observation of comparable neurological and psychiatric risks just after (compared with just before) emergence of the omicron variant suggests an ongoing neuropsychiatric burden of COVID-19 even with variants that lead to otherwise less severe disease.
Second, the risk profile in different age strata, especially in children, has not been well characterised.
8
Hirt J
Janiaud P
Gloy V
et al.
Validity of reported post-acute health outcomes in children with SARS-CoV-2 infection: a systematic review.
Neurological manifestations of COVID-19 in paediatric populations (aged <18 years) have been reported,
9
Ray STJ
Abdel-Mannan O
Sa M
et al.
Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study.
but only one controlled study has investigated the risk of neurological and psychiatric outcomes after SARS-CoV-2 infection.
10
Roessler M
Tesch F
Batram M
et al.
Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19.
This study was limited to a 3-month follow-up period and measured neurological and psychiatric outcomes as two broad categories, without reporting the risk of individual diagnoses.
Third, whether or not risk profiles have changed with the emergence of different variants is unknown; in particular, whether or not the omicron (B.1.1.529) variant, which has a lower mortality rate and better acute outcomes than the alpha (B.1.1.7) and delta (B.1.617.2) variants
11
Wang L
Berger NA
Kaelber DC
Davis PB
Volkow ND
Xu R
COVID infection rates, clinical outcomes, and racial/ethnic and gender disparities before and after omicron emerged in the US.
,
12
Maslo C
Friedland R
Toubkin M
Laubscher A
Akaloo T
Kama B
Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 omicron wave compared with previous waves.
,
13
Nyberg T
Ferguson NM
Nash SG
et al.
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
and a different symptom profile,
14
Menni C
Valdes AM
Polidori L
et al.
Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study.
also leads to fewer neurological and psychiatric sequelae.
We used electronic health records to investigate these three questions. We assessed the 2-year risk trajectories of 14 neurological and psychiatric diagnoses in three age groups (children younger than 18 years, adults aged 18–64 years, and older adults aged ≥65 years), and if and when these risks returned to baseline. Then we compared these risks between patients diagnosed just after versus just before the emergence of the alpha, delta, and omicron variants.
Results
We extracted data for 1 487 712 patients with a recorded diagnosis of COVID-19 between Jan 20, 2020, and April 13, 2022, from the TriNetX Analytics database, of whom 1 284 437 were adequately matched (ie, standardised mean difference of <0·1 for each covariate) to an equal number of patients with another respiratory infection. Both matched cohorts comprised 185 748 children (aged <18 years), 856 588 adults (aged 18–64 years), and 242 101 older adults (aged ≥65 years). In the matched COVID-19 cohort, mean follow-up was 213 days (SD 204; median follow-up 146 days [IQR 20–364]), and in the matched other respiratory infection cohort, the mean follow-up was 223 days (SD 203; median 153 days [IQR 41–399]; table 1; appendix pp 15–26). In the matched COVD-19 cohort, 741 806 (57·8%) patients were female and 542 192 (42·2%) were male; in the matched comparator cohort with another respiratory infection, 741 696 (57·7%) were female and 542 305 (42·2%) were male.
Table 1Baseline characteristics for the whole COVID-19 cohort and the matched cohorts of COVID-19 patients and patients diagnosed with another respiratory infection
Data are mean (SD) and n (%). For clarity purposes, apart from race, only characteristics with a prevalence over 5% in the unmatched COVID-19 cohort are shown here; the same table with all characteristics included is presented in the appendix (pp 15–17).
The 2-year risk trajectories for each outcome, and for any first outcome, are shown in figure 1 and summarised in table 2 in terms of three key statistics: HR at 6-months, risk horizon, and time to equal incidence. In terms of 6-months HRs, compared with patients with other respiratory infections, patients diagnosed with COVID-19 were at increased risk of having any first neurological or psychiatric diagnosis, and of being diagnosed with an anxiety disorder, mood disorder, psychotic disorder, insomnia, cognitive deficit, dementia, epilepsy or seizures, ischaemic stroke, intracranial haemorrhage, and myoneural junction or muscle disease, but not encephalitis, Guillain-Barré syndrome, or parkinsonism (table 2). They were at a significantly lower risk of nerve, nerve root, and plexus disorder (table 2). All 6-month HRs, p values (including Bonferroni-corrected p values), death rates, markers of severity of the index infections, and results including death as a composite outcome are shown in the appendix (pp 27–28).
Figure 1Kaplan-Meier curves and time-varying HRs over the 2-year follow-up period for each outcome (A-N) and any first outcome (O) after COVID-19 or another respiratory infection in the propensity-score matched cohorts
Show full caption
Risk horizons are shown for panels A and B and time to equal incidence is shown on panel A; risk horizons and time to equal incidence for all other outcomes are shown in table 2. Shaded areas around curves show 95% CIs.
Table 2Risk of neurological and psychiatric sequelae at 6 months, risk horizon, and time to equal incidence for each diagnosis after COVID-19 versus after other respiratory infections, in the propensity-score matched population
The risk horizon is the time at which the time-varying hazard ratio returns to 1 (ie, the baseline risk in the comparison cohort). The time to equal incidence is the time at which the cumulative incidences of the two cohorts become equal. The risk horizon and time to equal incidence are only included for outcomes with a significantly increased hazard ratio at 6 months; for outcomes that did not reach the risk horizon or time to equal incidence within the follow-up period (up to 730 days), they are shown as not reached (NR).
The results for children, adults and older adults are presented in the appendix (pp 12–14, 39–31). In terms of HRs at 6 months, four main differences from the whole cohort were observed (figure 2). First, in children, unlike older groups, there was no increased risk of mood or anxiety disorder. Second, children, unlike other age groups, were at an increased risk of encephalitis after COVID-19 compared with other respiratory infection. Third, unlike adults and older adults who were at a reduced risk of nerve, nerve root, and plexus disorder compared with the matched cohort of patients with another respiratory infection, children were at an increased risk of this outcome after COVID-19. Fourth, the risk of any first diagnosis was higher in older adults than in younger age groups, reflecting their higher HRs for most individual diagnoses.
Figure 2Hazard ratios for the 6-month risk of neurological and psychiatric sequelae after COVID-19 versus another respiratory infection, in different age groups, in the propensity-score matched population
Show full caption
Data are hazard ratios with 95% CIs. Children defined as younger than 18 years, adult, aged 18–64 years, and older adults as aged 65 years or older
Besides the 6-months HRs, 2-year risk trajectories can be summarised by their risk horizon and time to equal incidence. In terms of these two statistics, outcomes fell into three categories (figure 1, table 2; see appendix pp 12–14, 29–31 for a breakdown by age groups). In a first category (figure 1A), within 2 years, HRs have returned to baseline (eg, mood disorder at 43 days, anxiety disorder at 58 days, and ischaemic stroke at 66 days) and an equal cumulative incidence between cohorts was subsequently reached (eg, mood disorder at 457 days, anxiety disorder at 417 days, ischaemic stroke at 712 days). Therefore, these outcomes showed a transient risk trajectory, because no increase in cumulative incidence was observed at 2 years despite an increased risk at 6 months. In a second category (figure 1B), a risk horizon was reached within 2 years but equal incidence was not reached. These outcomes showed a persistent risk trajectory: an increased cumulative incidence persists after 2 years in the COVID-19 cohort, but there is no increased risk of new diagnoses past the risk horizon. In a third category (figure 1C), which includes cognitive deficit, dementia, psychotic disorders, and epilepsy or seizures, HRs remained greater than 1 at the end of the follow-up period. These outcomes followed an ongoing risk trajectory, wherein new diagnoses were still being made more frequently after COVID-19 diagnosis than after a diagnosis of another respiratory infection up to 2 years after the index event. These different risk trajectories were broadly similar in children, adults, and older adults (appendix pp 12–14, 29–31), with three exceptions. In children, cognitive deficit followed a transient risk trajectory, with a finite risk horizon (75 days) and a finite time to equal incidence (491 days). Conversely, intracranial haemorrhage and nerve, nerve root, and plexus disorder had an ongoing risk trajectory in children, such that they did not reach a risk horizon (nor therefore a time to equal incidence) within 2 years.
The endpoints of the 2-year risk trajectories can be summarised in terms of cumulative incidence at the end of the 2-year follow-up period and the proportion of patients with each diagnosis who subsequently died during the follow-up (figure 3; appendix pp 32–33). Interpretation of these findings, and the absence of differences between the matched cohorts with COVID-19 and other respiratory infection, should take into account the broadening 95% CI towards later stages of follow-up (as shown in the Kaplan-Meier curves in figure 1), due to the decreasing number of people contributing data. We found no evidence of a greater overall risk of any first neurological or psychiatric diagnosis after COVID-19 than after any other respiratory infection. This finding reflects the large contribution of mood and anxiety disorders to any first diagnosis, and their time to equal incidence. In older adults, death was common in those who received a neurological or psychiatric diagnosis regardless of whether they had COVID-19 or another respiratory infection, exceeding 50% for several of the neurological disorders and for psychotic disorder. The significantly higher 2-year cumulative incidences observed after COVID-19 (vs another respiratory infection) for outcomes with persistent or ongoing risk trajectories were reflected differently across age groups: the difference in incidence of cognitive deficit and dementia between cohorts was more noticeable for older adults than for adults or children; that of myoneural junction or muscle diseases was predominantly seen in children and adults but not older adults; that of epilepsy or seizures was significant only in children, and the risk of psychotic disorder was more evident for children and older adults than for adults.
Figure 3Cumulative incidence of neurological and psychiatric diagnoses at 2 years after COVID-19 versus another respiratory infection, in different age groups, by mortality status at 2 years (or censorship date), in the matched cohorts
Show full caption
The proportion next to each bar corresponds to the overall incidence of the outcome within that age group and the number in brackets indicates the proportion of those with the outcome who died within 2 years. Estimated numbers of deaths that are lower than 120 are unreliable and therefore not reported. 95% CIs for each estimate, and p values for each outcome, are in the appendix (p 32). NR=not reported *p<0·05. †p<0·01. ‡p<0·001.
For our analysis of risk of outcomes with new variants, we compiled six additional US COVID-19 cohorts: the primary alpha (n=47 675), delta (n=44 835), and omicron (n=39 845) cohorts, and matched control cohorts of equal size diagnosed just before the emergence of alpha, delta, and omicron, respectively (baseline characteristics for each cohort are shown in the appendix [pp 34–42]). We found the risk profiles for each outcome evolved as new variants emerged (figure 4; appendix pp 43–46). We observed little change in terms of 6-month HRs between the patients diagnosed just before and just after the emergence of the alpha variant. By contrast, significantly higher 6-month risks of anxiety disorders, insomnia, cognitive deficit, epilepsy or seizures, and ischaemic strokes, but a lower risk of dementia, were observed in those diagnosed just after the emergence of the delta variant than in those diagnosed just before. These risks were compounded by a higher risk of death just after the emergence of the delta variant, such that the risk of composite outcomes of individual sequelae or death was all significantly higher for those diagnosed just after emergence of the delta variant (including the composite of dementia or death). Patients diagnosed with COVID-19 just after (vs just before) the emergence of the omicron variant were at an increased risk (over 140 days of follow-up) of dementia, mood disorders, and nerve, nerve root, and plexus disorders, and at a broadly similar risk of most other outcomes. However, risks were more than offset by a substantially lower risk of death, such that the composite risks of each outcome and death were significantly lower than among those diagnosed just before the emergence of omicron.
Figure 4Risk of neurological and psychiatric outcomes after versus before the emergence of different SARS-CoV-2 variants, in the USA
Show full caption
(A) Daily incidence of SARS-CoV-2 infection per million people in the USA (rolling 7-day average), by dominance of different variant. Areas surrounded by solid black lines indicate the time during which the cohort for a particular variant had their COVID-19 diagnosis. Areas surrounded by dotted black lines indicate the time during which the preceding variant cohort had their COVID-19 diagnosis. (B) Hazard ratios for the 6-month risk (140-days risk for omicron) of neurological and psychiatric sequelae, either analysed in isolation or as composite outcomes with death (ie, outcome or death). Hazard ratios with their 95% CIs and p values for each outcome, are in the appendix (pp 43–46) *p<0·05. †p<0·01. ‡p<0·001.
Discussion
In this analysis of retrospective cohort studies, in addition to supporting previous findings of an increased risk of a range of neurological and psychiatric diagnoses in the first 6 months after COVID-19 diagnosis,
3
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we found substantial differences in the trajectories of these risks within the first 2 years after diagnosis. We also found that risk profiles and trajectories vary in children compared with adults and older adults, and differ between variants of SARS-CoV-2.
We summarised risk trajectories using risk horizons and times to equal incidences and our findings are of interest to both patients and clinicians. For instance, from the risk horizons, if no anxiety disorder has been diagnosed within 2 months of a COVID-19 diagnosis then, from that time onwards, a patient can be reassured that their risk is no longer any greater than after another respiratory infection. If a patient had developed an ischaemic stroke within 2 months of a COVID-19 diagnosis, it is plausible that the COVID-19 diagnosis contributed (whether directly or indirectly) to its occurrence, but beyond 2 months, other causes should be actively considered. Risk trajectories are also informative for public health. An increase in the number of new cases of COVID-19 is likely to lead to an increase in the number of cases of mood and anxiety disorders but this will be short lived. By contrast, the absence of risk horizons within the first 2 years of a COVID-19 diagnosis (ie, ongoing risk trajectories) for some diagnoses (eg, psychotic disorders, epilepsy or seizures, cognitive deficit, and dementia) indicate that patients and clinicians must remain vigilant about the possibility of these delayed sequelae. These findings also suggest that service provision needs to be reinforced and sustained, because new cases are likely to occur for a considerable time after the pandemic has subsided. The time to equal incidence informs us about what happens after the risk horizon has been reached. On the one hand, the risks might become approximately equal in the two cohorts so that a so-called COVID excess remains throughout follow-up and the time to equal incidence is never reached (ie, persistent risk trajectories), which was the case for insomnia and myoneural junction or muscle disease. On the other hand, the risks might reverse, with more new diagnoses in the other respiratory infection cohort than in the COVID-19 cohort after the risk horizon, so that a time to equal incidence is eventually reached (ie, transient risk trajectories), as seen for anxiety and mood disorders.
Another important aspect of outcome trajectories is the proportion of people who received a neurological or psychiatric diagnosis who subsequently died. All-cause mortality was substantial among older adults diagnosed with neurological or psychiatric sequelae both after COVID-19 diagnosis and after another respiratory infection—notably, those with epilepsy or seizures, dementia, cognitive deficit, and psychotic disorder. The fact that similar proportions of patients with these outcomes died in both cohorts suggests that this high mortality reflects general physical ill health rather than being related to SARS-CoV-2 infection itself.
The mortality rate in older patients also raises the issue of death as a competing risk.
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Because both death and the individual outcomes tend to be more common after COVID-19, the survivorship bias introduced when analysing individual outcomes brings HRs closer to 1. Individual outcomes, rather than composite outcomes with death, better reflect the burden of post-COVID-19 sequelae on health systems whereas composite outcomes are probably more informative to patients. Some outcomes have an HR of less than 1 when analysed in isolation and an HR of more than 1 when investigated as part of a composite outcome with death. Outcomes in this category are less likely to occur after COVID-19 versus after any other respiratory infection, but this might at least partly be because patients died before they could be diagnosed with these outcomes. The role of death as a competing risk likely differs between age groups because death rates vary substantially, which might contribute to apparent differences in risk profiles.
Compared with adults and older adults, children were at a particularly increased risk of epilepsy or seizures, encephalitis, and nerve, nerve root, and plexus disorder, leading to significantly higher cumulative incidence after 2 years (albeit with small absolute risks) in this age group. The persistence and severity of these outcomes cannot be determined from our study, but some will probably have deleterious consequences for children’s health and physical and educational development. Therefore, these findings inform the risks and benefits of vaccination (and other preventive measures) against COVID-19 in paediatric populations. Reassuringly, unlike adults, children were not at an increased risk of mood and anxiety disorders after SARS-CoV-2 infection (even in the first 6 months) and cognitive deficit in children had a transient risk trajectory rather than ongoing risks as seen in older groups. The difference in profiles and trajectories of risks in children might indicate that the pathogenesis of COVID-19 sequelae is different in some respects from that of adults.
The risk of neurological and psychiatric diagnoses of COVID-19 was greater with the emergence of the delta variant (eg, for cognitive deficit, epilepsy or seizures, and ischaemic strokes) than just before its emergence. These risks were compounded by an increased risk of death (consistent with existing literature
23
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Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study.
)—for example, the HR for the composite of death or cognitive deficit was 1·38 (95% CI 1·27–1·48) whereas the HR for a diagnosis of cognitive deficit alone was 1·13 (1·02–1·26). Compared with just before the emergence of omicron, the neurological and psychiatric profile just after the emergence of omicron was broadly similar. For instance, we found no difference in the risk of cognitive deficit, epilepsy or seizures, ischaemic stroke, and psychotic disorder, and higher risks of some outcomes (eg mood disorder). All risks were largely offset by a reduced risk of death after the emergence of omicron (consistent with existing literature
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). The decreased composite risks of death and neurological or psychiatric sequelae are reassuring for patients. However, the ongoing risk of individual outcomes indicates that health services will likely continue to face a similar rate of these post-COVID-19 diagnoses even with SARS-CoV-2 variants that lead to otherwise less severe disease.
The possible mechanisms underlying neurological and psychiatric consequences of COVID-19 remain to be determined in longitudinal and multifaceted studies.
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Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.
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Sequelae in children might in part be driven by a post-infectious immune-mediated mechanism such as acute disseminated encephalomyelitis (ADEM), as has been suggested in a prospective study of 52 children hospitalised with COVID-19.
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This is consistent with our observations of an increased risk of encephalitis in children only, and a higher rate of post-COVID epilepsy or seizures in children. In the whole cohort, the finding of a persisting increased risk of cognitive deficit and dementia, psychotic disorder, and epilepsy or seizures 2 years after SARS-CoV-2 infection suggests that any underlying mechanism must have ongoing activity well past the acute infection (e.g. endotheliopathy might lead to a damaged or fragile cerebral vasculature at risk of thrombotic events or recurrent leakage
27
Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease.
). Notably, mood and anxiety disorders followed a different pattern than most other outcomes: their elevated risk subsided within 2 months, their cumulative incidence after 2 years was not increased, and children were not at greater risk at any stage after COVID-19 than after other respiratory infections. One possible explanation is that COVID-19 precipitates mood and anxiety disorders in individuals with an underlying predisposition, via a short-lived stress-related pathogenesis to which children are less susceptible.
Our study has specific limitations in addition to those inherent in electronic health records studies. First, our COVID-19 cohorts are probably enriched for symptomatic cases because self-diagnosed or asymptomatic COVID-19 is less likely to be coded in the health record. This is also true of the comparator cohort and their respiratory infections, and so HRs are less affected by this limitation than are incidences. Second, COVID-19 appeared to be more severe than other respiratory infections, but the mediation of our results by severity of the illness was not analysed. However, mediation by several markers of severity has been tested in our previous study,
4
Taquet M
Geddes JR
Husain M
Luciano S
Harrison PJ
6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.
in which we showed that severity explains part, but not all, of the association between COVID-19 and specific neurological and psychiatric outcomes. Third, only individuals who were diagnosed early in the pandemic contributed data for the whole 2-year follow-up. This is a subgroup within the whole cohort that might not be representative of the whole cohort. Future studies should clarify risks at the 2-year time point once larger sample sizes with longer follow-up become available. Fourth, our allocation of cohorts to study variants is based on epidemiological incidence data of different variants, not individual genotyping. Hence, these cohorts are likely to contain a few cases of other variants, which we factored into the statistical power calculation. The presence of patients with different variants in each variant cohort will bring HRs closer to 1 and so differences between variants would likely be more substantial if individual genotyping were possible. Fifth, vaccination status (used in matching) is probably under-reported in TriNetX, because the prevalence of vaccination was low in both cohorts. This under-reporting might affect HRs calculated when comparing COVID-19 cohorts before and after the emergence of new variants. Selecting time windows that were close to each other mitigates this effect, but does not eliminate it. Previous vaccination is associated with reduced or unchanged risks of most neurological or psychiatric outcomes.
28
Taquet M
Dercon Q
Harrison PJ
Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections.
Therefore, the higher number of vaccinated people after (vs before) the emergence of each variant might have decreased the observed HRs. Sixth, children and adolescents were grouped together, so further studies are needed to characterise the risks in different paediatric subgroups. Seventh, although in-hospital mortality data are well captured in TriNetX, out-of-hospital mortality reporting is more variable and linkage with mortality indices is only partial, so our incidence estimates will be underestimates and should be interpreted cautiously; but HRs for composite outcomes should not be affected to the same extent. Eighth, we do not know the severity or course of each disorder after diagnosis, or whether or not these are similar after COVID-19 and after other respiratory infections.
In summary, post-COVID neurological and psychiatric outcomes followed different risk trajectories: the risk of cognitive deficit, dementia, psychotic disorder, and epilepsy or seizures remained increased at 2 years after a COVID-19 diagnosis, while the risks of other diagnoses (notably, mood and anxiety disorders) subsided early and showed no overall excess over the 2-year follow-up. Children are not at increased risk of mood or anxiety disorders (even over the first 6 months) but share adults’ risk of several other diagnoses. The comparable risks seen after the emergence of omicron indicate that the neurological and psychiatric burden of COVID-19 might continue even with variants that lead to otherwise less severe disease. These findings are relevant for policy makers involved in anticipating and addressing the health burden of the pandemic, for researchers seeking to identify the mechanisms underpinning brain sequelae of COVID-19, and for patients and clinicians wishing to know the neurological and psychiatric risks following SARS-CoV-2 infections.
MT and PJH designed the study and defined cohort inclusion and exclusion criteria, outcome criteria, and analytical approaches. MT, QD, RS, LZ, JM, and IC contributed to data processing. MT did the data analyses. MT and PJH interpreted the data. MT wrote the report with input from PJH, RS, LZ, and JM. MT and PJH accessed and verified the underlying study data. MT is the guarantor. All authors had full access to all the data in the study, and had final responsibility for the decision to submit for publication.
The research focuses on mapping cis-regulatory components in human neurons that may be connected to the heredity of psychiatric disorders.
A Mount Sinai stem cell model may be able to shed light on the complex biology behind certain psychiatric disorders.
In order to map disease risk variants in human neurons, researchers from the Icahn School of Medicine at Mount Sinai used a unique stem cell model. This work may help shed light on the biological mechanisms behind neuropsychiatric diseases such as autism and schizophrenia.
Nan Yang, Ph.D., Assistant Professor of Neuroscience. Credit: Mount Sinai Health System
The group’s in vitro cellular model, which was recently published in the journal Cell Reports, was created to make it easier for future researchers to understand the disease mechanisms involving genome-wide association studies (GWAS) that characterize various risk alleles (common genetic variants conferring risk) for psychiatric disorders. This study could help develop better diagnostic methods for spotting mental problems years before patient symptoms manifest.
The research focuses on identifying cis-regulatory elements in human neurons that could be related to the heritability of psychiatric disorders. Cis-regulatory elements, which include enhancers and promoters, are non-coding
In recent years, GWAS have identified hundreds of gene regions associated with psychiatric disease, though understanding disease pathophysiology has been elusive. The functional genomics approach Dr. Yang and her team developed uses stem cell models that can help resolve the impact of patient-specific variants across cell types, genetic backgrounds, and environmental conditions. This unique approach effectively lays a foundation to translate risk variants to genes, genes to pathways, and pathways to circuits that reveal the synergistic relationship between disease risk factors within and between the cell types in the brain.
“Our research attempts to decode and transfer highly complex genetic insights into medically actionable information,” says Dr. Yang, who is a member of the Black Family Stem Cell Institute, The Friedman Brain Institute, and The Ronald M. Loeb Center for
You can watch Jake Tapper’s exclusive interview with Trevor Reed in a CNN Special Report: “Finally Home: The Trevor Reed Interview,” on CNN and CNN International on Sunday, May 22, at 8 p.m. ET.
“The psychiatric treatment facility, I was in there with seven other prisoners in a cell. They all had severe, psychological health issues — most of ’em. So over 50% of them in that cell were in there for murder. Or, like, multiple murders, sexual assault and murder — just really disturbed individuals,” Reed told CNN’s Jake Tapper in a newly released clip from the upcoming CNN Special Report, “Finally Home: The Trevor Reed Interview,” which airs Sunday night.
“And inside of that cell, you know, that was not a good place,” he added.
“There was blood all over the walls there — where prisoners had killed themselves, or killed other prisoners, or attempted to do that,” Reed continued. “The toilet’s just a hole in the floor. And there’s, you know, crap everywhere, all over the floor, on the walls. There’s people in there also that walk around that look like zombies.”
In the clip, which aired on CNN’s “New Day” Friday morning, Reed said he did not sleep for a couple of days out of fear of what the people in his cell might do to him.
“You felt they might kill you?” Tapper asked, to which Reed replied: “Yes. I thought that was a possibility.”
Reed said he believed he was sent to the facility as a punishment for his continued push to appeal his conviction. His return to the United States late last month ended a nearly three-year ordeal.
The former US Marine was sentenced to nine years in prison in July 2020 after being accused of endangering the “life and health” of Russian police officers in an altercation the previous year. Reed and his family have denied the charges against him.
Ultimately, Reed was returned to the US as part of a prisoner swap in exchange for Konstantin Yaroshenko, a Russian smuggler convicted of conspiring to import cocaine. The US commuted his sentence.
Behind the scenes, officials both inside and outside the US government had for years been working to get Reed released. Last month’s swap, one administration official told CNN, was the culmination of “months and months of hard careful work across the US government” that took place against the backdrop of growing tensions between Washington and Moscow — exacerbated dramatically by Russia’s brutal war on Ukraine.
It was the combination of factors around Reed’s case — including the urgent need to address his deteriorating health in prison, his family’s consistent activism which led to a meeting with Biden, and the situation in Ukraine — that led Biden to authorize the swap for Yaroshenko, a source told CNN last month.
‘I wouldn’t let myself hope’
Reed told Tapper that he felt like he would never return to the US, saying he didn’t have confidence that he would ever get out of the Russian prison.
“And a lot of people are not going to like what I’m gonna say about this, but I kind of viewed their — having hope as being a weakness,” he said. So I did not wanna have that hope of, like, me, you know, being released somehow and then have that taken from me.”
“You denied yourself hope?” Tapper asked.
“Yeah,” Reed said. “I wouldn’t let myself hope.”
But Reed’s loved ones in the US held onto their hope throughout his imprisonment.
Reed’s family are the only relatives of a detainee held in Russia to have met with President Joe Biden to make their case. And they say that meeting was crucial to bringing Reed home.
“We believe that that meeting with the President is what made it happen,” Joey Reed, Trevor’s father, said last month. Trevor’s mother, Paula, also called the meeting “a tipping point.”
Reed and his family have vowed to continue their activism and fight for Americans unlawfully detained abroad.
Two other Americans, Paul Whelan and Brittney Griner, remain detained in Russia.
A senior administration official told CNN last month that they do not necessarily see Reed’s successful repatriation as translating to momentum for Whelan’s and Griner’s cases, but said the US government will continue to press for their release, and the channel for potential swaps will remain open.
Secretary of State Antony Blinken spoke to Griner’s wife, Cherelle Griner, on Saturday.
According to a senior State Department official, the top US diplomat relayed that Griner’s release is a top priority for the department and has his full attention.
Griner’s family, in a statement obtained by CNN, said they are “grateful for the time Secretary Blinken took on his recent call with Cherelle and look forward to her face-to-face meeting with the President.”
CLARIFICATION: This story has been updated to reflect that Trevor Reed’s parents are the only relatives of a detainee held by Russia to have met with President Joe Biden.
CNN’s Jennifer Hansler, Kylie Atwood and Kevin Liptak contributed to this report.
People diagnosed with a psychiatric condition were more likely to catch Covid-19 after being fully vaccinated, according to a new study.
Published this month in JAMA Open Network, the study used health records from more than 260,000 people from the U.S. Department of Veterans Affairs.
The correlation, researchers found, was much stronger in people 65 and older. This could be the result of decades of strife — from having a psychiatric condition and the circumstances that can lead to psychiatric conditions — battering the immune system.
“There’s a lot of evidence to suggest that chronic stress, traumatic stress, and psychiatric conditions can actually accelerate cellular aging,” Aoife O’Donovan, an associate professor of psychiatry at the University of California, San Francisco and one of the study authors, tells Inverse. “It’s putting you at risk for appearing older biologically, and for your immune system, in particular, to function like the immune system of someone who’s older than you, and that’s certainly seen in patients with psychiatric disorders.”
What’s New — People with any psychiatric diagnosis were 3.7 percent more likely to develop a breakthrough infection of Covid-19, the researchers found. This was after researchers adjusted calculations to account for relevant factors more common to V.A. patients.
Among the types of diagnoses, non-alcohol substance abuse issues had the greatest correlation to breakthrough cases, increasing risk by 16 percent. This was not a surprise, says O’Donovan. Addiction causes people to increase risk-taking behaviors, and the pandemic created an environment where everything from hugging to eating at a restaurant was a risk-taking behavior.
The pandemic created a new minefield for everyday risk assessment.ISAAC LAWRENCE/AFP/Getty Images
Next were adjustment disorders — ones in which someone feels unusual stress or sadness in response to a life event, linked to a 13-percent increase in risk, followed by anxiety conditions (eight percent), bipolar disorder (seven percent) alcohol use disorder (five percent), depression (five percent), and post-traumatic stress disorder (three percent).
There was a stark difference when the results were broken up between subjects younger than 65 and older. Overall, people older than 65 who had a psychiatric diagnosis were five percent more likely to have a breakthrough Covid-19 infection than others of that age. The risk shot up for each condition, more than doubling for PTSD and increasing by sevenfold for people with bipolar condition.
For those under 65, the association with depression, PTSD, bipolar disorder, and alcohol use disorders was reduced to the point of being statistically insignificant.
People under 65 with psychotic conditions — ones like schizophrenia that involve a break from reality —were less likely to get Covid-19 post-vaccination, which O’Donovan chalks up to social isolation. This echoes an Israeli study of people with schizophrenia; they were less likely to get Covid-19 in general. That study’s authors partially attributed those results to social isolation as well.
But for those older than 65, psychotic conditions were highly correlated with the risk of a breakthrough infection, increasing risk by a whopping 26 percent.
The paper theorizes that “the vulnerabilities associated with psychiatric disorders may interact with the vulnerabilities associated with older age to confer greater risk for incident breakthrough infection.”
How They Did It — Researchers used the records of 263,697 fully vaccinated V.A. patients, 51 percent of whom had at least one psychiatric diagnosis. About 15 percent experienced a breakthrough infection.
Using data exclusively from the V.A. was not ideal, O’Donovan says. This group is not representative of the entire U.S. population. People who go to the V.A. are more likely to be of lower socioeconomic status, have several medical conditions, and live in a rural area. They are also generally older and almost all men.
However, “the V.A. did a very good job of gathering all of this information and releasing it quickly,” she says. Without that kind of real-time record-keeping, she says, it would be incredibly difficult to get this much information on a recent phenomenon (“breakthrough Covid-19” is a concept that didn’t exist 16 months ago).
And with so much data, researchers can make adjustments to diminish the effect of factors that would color the results.
The findings “are unlikely to be specific to Covid-19”
Another shortcoming: The V.A. generally sorts patients into two age categories: under 65 and older than 65, ubiquitous in government records because 65 is the start point for Social Security and Medicare. This meant it was impossible to see when the increased risk of getting a breakthrough infection for people with psychiatric conditions really begins.
“We’d know more if we had 10-year brackets,” says O’Donovan.
Why It Matters — The study is yet another piece of research indicating that psychiatric conditions impact the immune system, a finding that could be important for more than today’s issue du jour.
The findings “are unlikely to be specific to Covid-19,” says O’Donovan, “but are much more likely to generalize to other infections. An obvious issue is risk for the flu and prevention of the flu.”
These findings give reason to consider mental health when crafting responses to Covid-19 and other infectious disease outbreaks.
Researchers would like to know if an additional booster would help people with psychiatric conditions.NurPhoto/NurPhoto/Getty Images
“This study adds to a body of literature that’s telling us that patients with psychiatric disorders may well be — and do appear to be — a vulnerable population in this pandemic that might need targeted prevention efforts,” says O’Donovan. “We may need to be focused on integrating Covid prevention into mental health care and also integrating mental health care into our Covid prevention strategies because the two are so interlinked.”
What’s Next — O’Donovan would like to embark on a project that investigates the effectiveness of Covid-19 vaccines on people with psychiatric conditions, one that might indicate an added need for boosters.
Psychiatry’s most influential diagnostic manual has a new disorder in its latest edition: prolonged grief.
Why it matters: The diagnoses could open up new ways of treating mental distress associated with grief and have that care paid for by insurers, the New York Times reports.
The addition of prolonged grief disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM) comes at a time when many in the U.S. are grappling with loss related to the pandemic.
What they’re saying: The inclusion of the disorder “will mean that mental health clinicians and patients and families alike share an understanding of what normal grief looks like and what might indicate a long-term problem,” said APA CEO Saul Levin in a statement last fall about the move to add prolonged grief to the DSM.
But, but, but: The move was not without controversy, with some providers arguing the move categorizes a basic element of human emotions as a disorder and could lead to false positives, per the Times.
